UNIT 1

HISTORICAL BACKGROUND AND DEVELOPMENT OF PROFESSION OF PHARMACY

Pharmacy

►Pharmacy is a science and technique of preparing as well as dispensing of drugs and

medicines.

►It is a health profession that links health sciences with chemical sciences and aims to
ensure the safe and effective use of pharmaceutical drugs.

►The scope of pharmacy practice includes traditional roles such as compounding and
dispensing medications and it also includes more modern services related to health care
including clinical services, reviewing medications for safety and efficacy and providing drug
information.

►Pharmacists are the experts on drug therapy and are the primary health professionals who
optimize use of medication for the benefit of the patients.

►The word pharmacy is derived from its root word Pharma which was a term used since the
15th–17th centuries.

►The original Greek roots from pharmakos imply sorcery or even poison.

►In addition to pharma responsibilities, the pharma offered general medical advice and a
range of services that are now performed solely by other specialist practitioners such as
surgery and midwifery.

►The pharma (as it was referred to) often operated through a retail shop which, in addition
to ingredients for medicines, sold tobacco and patent medicines.

► The Greek word pharmakeia derives from pharmakon meaning "drug", "medicine" (or
"poison").

►In its investigation of herbal and chemical ingredients, the work of the pharma may be
regarded as a precursor of the modern sciences of chemistry and pharmacology, prior to the
formulation
Pharmaceutics

►Is the discipline of pharmacy that deals with the process of turning a new chemical entity
(NCE) or old drugs into a medication to be used safely and effectively by patients.
►It is also called the science of dosage form design.
►There are many chemicals with pharmacological properties, but need special measures to
help them achieve therapeutically relevant amounts at their sites of action.
►Pharmaceutics helps relate the formulation of drugs to their delivery and disposition in the
body.
►Pharmaceutics deals with the formulation of a pure drug substance into a dosage form.
Branches of pharmaceutics include:

• Pharmaceutical formulation
• Pharmaceutical manufacturing
• Dispensing pharmacy
• Pharmaceutical technology
• Physical pharmacy
• Pharmaceutical jurisprudence
HISTORY OF PHARMACY

►The pharmacy profession can be traced back at least as far as the Sumerian population,
living in modern day Iraq.

►From around 4000 BC, they used medicinal plants such as liquorice, mustard, myrrh and
opium.

►There were separate people who worked to prepare medicines, as a separate role from
diagnosis and treatment which was carried out by medics.

►These precursors to pharmacists also combined their role with that of a priest.

►The Sumerians wrote the earliest surviving prescriptions from at least 2700 B.C.(so nearly
5000 years ago).

►The Ancient Egyptians had specific preparers of medicine, known as Pastophor.

►Pharmacy was viewed as a high status branch of medicine, and again, like the Sumerians,
these pharmacists were also priests who worked and practised in the temples.

►From surviving papyrus scrolls, notably the Ebers Papyrus which dates from 1500 BC, we
know that the Egyptians made and used infusions, ointments, lozenges, suppositories, lotions,
enemas and pills.

►The Ebers Papyrus includes 875 prescriptions and 700 drugs.

►Meanwhile, in China in about the same era (2000 BC), a man called Shen Nung wrote the
first Pen T’sao or native herbal, which contained descriptions of 365 plant-based drugs.

►Stalls and shops selling medicinal goods existed around 1900 B.C. in the town of Sippara
on the Euphrates river. However, the earliest recorded shop dealing with sales of medicines in
London was opened in 1345.

►The word 'pharmacist' was first used in a publication in England in 1834.

►At the beginning of the 19th century most people working in this area would have called
themselves chemists and druggists.

►The terms pharmacist and pharmaceutical chemist (now usually shortened to chemist)
came later in the 1800s.

►The word “pharmacy” has a much longer history in England.

►Chaucer in The Knight’s Tale (written around 1386) uses the word to describe a medical
preparation of plants “farmacies of herbs.”

►The term apothecary, often used between the 1600s and 1800s, does not refer to the
chemist and druggist, or pharmacist.
►It was used for individuals living in London who had passed the examinations of the
Worshipful Society of Apothecaries of London, founded in 1617, or to their often less well
qualified counterparts in the provinces.

►The role of apothecary developed out of the role of Spicer or Pepperer or grocers,
someone whose trade included crude drugs and prepared medicines.

►The Grocers had their own Guild – professional body in the City of London- from the
13the century.

►The Apothecaries split from them in 1617 to form their own Society.Although the
apothecary's practice included a strong dispensing element.

►Apothecaries were also examining and treating patients, but they did not charge for these
services – only for the medicines supplied.

►Following a ruling in the Rose Case (1701-1703), apothecaries became legally ratified
members of the medical profession, able to prescribe as well as dispense medicines.

►As apothecaries moved into a more advisory role, pharmacists (or chemists and druggists)
could develop their own area of preparation and supply of medicines. However, this put them
in competition with the apothecaries who were also still involved in the same area.

►The apothecaries attempted to control the chemists and druggists' activities in 1748 with a
proposed new law to control the supply of medicines.

►In the early 1800s, an Association was formed to put together a proposal to Parliament to
set up a body that examined and regulated apothecaries, surgeon-apothecaries, midwives and
dispensing chemists.

►The chemists and druggists took action, arguing that they were best placed to set their own
standards, as they had more experience in making up prescriptions and making medicines
than the apothecaries, so they should not be put under their control.

►The chemists and druggists won their argument when the Apothecaries Act of 1815 was
finally created, the apothecaries did not have control over making medicines.
SOME KEY DATES IN PHARMACY HISTORY

YEAR EVENTS
The alkaloid quinine was first extracted from the bark of cinchona trees by two
1820
French chemists, Pierre Joseph Pelletier and Joseph Biename Caventou.
1874 Diamorphine or Heroin was first synthesised from morphine.
First edition of The Extra Pharmacopoeia published, edited by William
1883
Martindale and Dr Wynn Westcott.
1899 Aspirin, was launched by the German company.
Salvarsan, the first 'magic bullet' drug, effective against syphilis was discovered
1910
by Paul Ehrlich and Dr Sahachiro Hata.
1915 Medicine stamp duty was doubled as a wartime fundraiser.
The Venereal Disease Act prohibited the advertising of medicines for VD and
selling
1917
mixtures containing scheduled substances. It introduced the concept of
'prescription only' medicines.
The Dangerous Drugs Act regulated the import and sale of potential 'drugs of
addiction',
1922
including the derivatives of opium, cocaine and cannabis so widely used in
proprietary remedies.
1928 Penicillin discovered by Alexander Fleming.
1938 The Food and Drugs Act prohibited the adulteration and mislabeling of drugs.
The Cancer Act restricted the advertisement of products claiming to treat
1939
cancer.
Under the Finance (No. 2) Act purchase tax was imposed on a range of goods
1940
including most drugs and medicines.
The Pharmacy and Medicines Act repealed the old medicine stamp duty. It
forbade the general advertisement of products claiming to treat a number of
1941 specific illnesses including Bright's disease, cataract epilepsy and TB, or to be
effective in procuring an abortion. For the first time manufacturers were
required to list the active ingredients of products on their packaging.
The National Health Service made prescription medicine available to all. Until
the introduction, in the 1950s, and subsequent hefty increasing of prescription
1948
charges, proprietary medicines were no longer seen as a cheap alternative to
seeing the doctor.
Ibuprofen was first synthesised by a team at the Boots Pure Drug Company in
1961
December.
Introduction of Adverse Drug Reaction 'yellow card' scheme in reponse to the
1964
thalidomide tragedy of 1961.
Industry
►In ancient India the sources of drugs were of vegetable, animal and mineral origin.
►They were prepared empirically by few experienced persons. Knowledge of that medical
system was usually kept secret within a family.
►There were no scientific methods of standardization of drugs.
Muslim rule in India
►The Indian system of medicine declined during the Muslim rule while the Arabic or the
Unani system flourished.
British rule in India
►Allopathic system came into India with the British traders who later become the rulers.
►Under British rule this system got state patronage.
►At that time it was meant for ruling race only. Later it descended to the people and become
popular by the close of 19th Century.
Before 1940: Initially all the drugs were imported from Europe. Later some drugs of this
system began to be manufactured in India.
1901: Establishment of the Bengal Chemical and Pharmaceutical Works, Kolkata by
Acharya Prafulla Chandra Ray.
1903: A small factory at Parel (Bombay) by Prof. T.K. Gujjar.
1907: Alembic Chemical Works at Baroda by Prof. T.K. Gujjar.
►Drugs were mostly exported in crude form and imported in finished form.
►During World War-I (1914 – 1920) the imports of drugs were cut-off. Imports of drugs
were resumed after the War.
►There was complete absence of any restrictions on the quality of drugs imported, so
manufacturer abroad took advantage of the situation. The consequences were as follows:
►Foreign manufacturers dumped inferior quality medicines and adulterated drugs.
►Markets were full of all sorts of useless and deleterious drugs were sold by unqualified
men.
Examples of maladies:
►Poisoning due to quinine.
►Putting of Croton oil into eye instead of Atropine solution.
►Selling of chalk powder tablets in place of quinine.
►Drug santonin was badly adulterated.
►Potent drugs like compounds of antimony and arsenic and preparations of digitalis were
dispensed without any standard.
►At that time few laws were there having indirect connection to drugs, but they were
insufficient.
YEAR AND ACT DESCRIPTION
1878 Opium Act Dealt with cultivation of poppy and the manufacture,
transport, export, import and sale of opium.
1889 Indian Merchandise Act Misbranding of goods in general
1894 Indian Tariff Act Levy of customs duty on goods including foods, drinks,
drugs, chemicals and medicines imported into India or
exported there from.
1898 Sea Customs Act Goods with ‘false trade description’ were prevented from
importing under this act.
1919 Poisons Act Regulated the import, possession and sale of poisons.

Indian Penal Code Some sections of IPC have mention of intentional

adulterations as punishable offence.
Some state-level law had indirect references to drugs:

YEAR AND ACT DESCRIPTION

1884 Bengal Municipal Act --------------------------------------------------
1901 City of Bombay District Municipal Concerned with food.
Act
1909 Bengal Excise Act --------------------------------------------------
1911 Punjab Municipal Act --------------------------------------------------
1912 United Provinces (now Uttar Refers to adulteration of foods and drugs.
Pradesh) Prevention of Adulteration Act
1914 Pujab Excise Act --------------------------------------------------
1916 United Provinces Municipalities Act Inspection of shops and seizure of adulterated
substances.
1919 Bengal Food Adulteration Act --------------------------------------------------
1919 Bihar and Orissa Prevention of --------------------------------------------------
Adulteration Act
1919 Madras Prevention of Adulteration Chiefly concerned with food adulteration
Act
1922 Bihar and Orissa Municipal Act -------------------------------------------------
1922 Central Provinces Municipalities -------------------------------------------------
Act
1925 Bombay Prevention of Adulteration ------------------------------------------------
Act
1929 Punjab Pure Food Act -------------------------------------------------
The laws were too superficial and had indirect link to drugs.
Drug enquiry committee
►Government of India on 11th August 1930 appointed a committee under the chairmanship
of Late Col. R.N.Chopra to see into the problems of Pharmacy in India and recommended the
measures to be taken.

►This committee published its report in 1931.

►It was reported that there was no recognized specialized profession of Pharmacy.

►A set of people known as compounders were filling the gap.

►Just after the publication of the report Prof. M.L.Schroff (Prof. Mahadeva Lal Schroff)
initiated pharmaceutical education at the university level in the Banaras Hindu University.

►In 1935 United Province Pharmaceutical Association was established which later
converted into Indian Pharmaceutical Association.

►The Indian Journal of Pharmacy was started by Prof. M.L.Schroff in 1939.

►All India Pharmaceutical Congress Association was established in 1940.

►The Pharmaceutical Conference held its sessions at different places to publicize Pharmacy
as a whole.

1937: Government of India brought ‘Import of Drugs Bill’; later it was withdrawn.

1940: Govt. brought ‘Drugs Bill’ to regulate the import, manufacture, sale and distribution of
drugs in British India. This Bill was finally adopted as ‘Drugs Act of 1940’.

1941: The first Drugs Technical Advisory Board (D.T.A.B.) under this act was constituted.
Central Drugs Laboratory was established in Calcutta

1945: Drugs Rule under the Drugs Act of 1940’ was established. The Drugs Act has been
modified from time to time and at present the provisions of the Act cover Cosmetics and
Ayurvedic, Unani and Homeopathic medicines in some respects.

1945: Govt. brought the Pharmacy Bill to standardize the Pharmacy Education in India.

1946: The Indian Pharmacopoeial List was published under the chairmanship of late
Col.R.N. Chopra. It contains lists of drugs in use in India at that time which was not included
in British Pharmacopoeia.

1948: Pharmacy Act 1948 published.

1948: Indian Pharmacopoeial Committee was constituted under the chairmanship of late Dr.
B.N. Ghosh.

1949: Pharmacy Council of India (P.C.I.) was established under Pharmacy Act 1948.

1954: Education Regulation have come in force in some states but other states lagged behind.
1954:Drugs and Magic Remedies (Objectionable Advertisements) Act 1954 was passed to
stop misleading advertisements (e.g. Cure all pills).

1955: Medicinal and Toilet Prepartions (Excise Duties) Act 1955 was introduced to enforce
uniform duty for all states for alcohol products.

1955: First Edition of Indian Pharmacopoeia was published.

1985: Narcotic and Psychotropic Substances Act has been enacted to protect society from the
dangers of addictive drugs.

►Govt. of India controls the price of drugs in India by Drugs Price Order changed from time
to time.
Pharmacy Education
The evolution of pharmacy education India can be traced to the first pharmacy course started
in December 1860 at madras medical college .At that time students were taught the art of
compounding, dispensing and labeling the instructions for use of various pharmacopoeial
preparations.

The formal pharmacy education started in India with the establishment of the first degree
level course in pharmacy in Banarad Hindu University (BHU) in1932. Professor Mahadev
Lal Schorff is regarded as the father of modern pharmacy for his pivotal role in stating a
two year bachelor course in pharmaceutical chemistry (B.Sc pharmaceutical Chemistry ) .In
July 1937 , a three years degree course ,Bachelor of pharmacy (B.Pharmacy) was started in
the Department of Pharmaceutics of BHU under the service of prominent teachers.

As the B.Pharm degree level education flourished far and wide , postgraduate education in
pharmacy was also pioneered in parallel ground .In April 1940 ,Banaras Hindu University
introduced a one year course of research that awarded the degree of Master of pharmacy
(M.Pharmay ) .Between 1952-53, the duration of M.pharm course was increased to 1.5 year
and the curriculum comprised classroom instruction in recent advancements in pharmacy
and chemistry of drugs followed by the research on a selected topic .In the later years,
programmes on research leading to Doctor of Philosophy (Ph.D), degree in pharmacy were
started .

In September 1994, the Government of India, made a very significant development in

pharmaceutical education with the establishment of National Institute of Pharmaceutical
Education and Research (NIPER) at Mohali. Punjab under the directorship of Dr.C.LKaul.
This institute serves as a center of excellence for advanced studies and research (M.Pharm
and Ph.D ) in Pharmaceutical science In 6 departments viz., pharmaceutical technology,
pharmaceutics, biotechnology , medicinal chemistry , natural products , pharmacology and
toxicology .

B.V.patel Pharmaceutical Education and Research Development Center (B.V.Patel PERD

Centre ) established in September 1990 near Ahmadabad under the directorship of H.L
Bhalla, is another pioneering institute that contributes to high standards in pharmaceutical
education and research by organizing programs and national and international symposia.

Pharmacy education in India is regulated by Pharmacy Council if India. Candidates who

intend t pursue their career in pharmacy must join in PCI approved colleges. The list of all
such colleges is available on the official website of the council (www.pic.nic.in)

Pharmacy education consist of blend of theory and practical classes and examination and
compulsory industrial or hospital training of varying duration depending on the educational
program selected.
Educational Programs in the Field of Pharmacy

The various pharmacy degree programs offered by different universities in India are as
follows,

1. Diploma in pharmacy (D.Pharm)

2. Bachelor of Pharmacy (B.Pharm)

3. Master of Pharmacy (M.Pharm)

4. Master of science in Pharmacy [MS(Pharm)]

5. Master of technology in Pharmacy [M.Tech (Pharm)]

6. Doctor of Pharmacy (Pharm.D)

7. Doctor of philosophy in Pharmacy (PhD)

1. Diploma in pharmacy (D.Pharm)

A.It is a two year courser approved by (PCI). It is the minimum qualification to get registered
as a pharmacist in India.

B.The minimum qualification for entry into D.Pharm is passing of any of the following
examination of t with Physics, chemistry and biology or mathematics.

❖ 10+ 2 examination (academic stream ) in science

❖ Intermediate examination in science
❖ First year of the three year degree course in science
❖ Pre-degree examination or
❖ Any other equivalent qualification approved by PCI

C. (D.Pharm requires) 2 years full time course plus 500 hours practical training. The
curriculum for D.Pharm is framed through education regulations of pharmacy Act

D.The course of study includes the study of following subjects in the first year and second
year.

The present D.Pharm curriculum was framed in 1991 and is similar in all the colleges
throughout the country.

Scope

A.D.Pharm program was designed and developed to train students to serve as pharmacists in
institutions or community.

B.They can render their services in either hospitals (private/government) or community

pharmacy (mostly private).
C.They can also work in pharmaceutical industries. However diploma-trained pharmacists are
usually less paid than other similarly qualified health professional (E.gs: Nurses, diagnostic
technicians etc). Even in the recently accepted Indian government's Sixth Pay Commission,
practicing pharmacists were placed in the lowest band and structure.

2. Bachelor of Pharmacy (B.Pharm)

A. It is a 4-year degree course regulated by AICTE.

B. Entry into B.Pharm course is given on the basis of marks obtained in the higher secondary
examination or on the basis of merit list rank obtained in an entrance examination conducted
by individual institutions or a state. The entrance exam for admission into first year B.Pharm
or Bachelor of engineering programs is jointly conducted in all states except Karnataka and
Tamilnadu where B.Pharm and other Medical degree entrance exams are conducted together.
It is usually observed that students who obtain a lower rank in the list enter into B-Pharm
program. D.Pharm degree holders can join B.Pharm program in the second year

C. The curriculum for B.Pharm varies across the universities that offer this program. Most of
the universities prescribe a blend of basic science (inorganic and organic chemistry, physical
chemistry and mathematics), basic pharmacy (Pharmacognosy, pharmacology,
pharmaceutics and pharmacy law) and advanced chemistry and analysis (medicinal
chemistry, biochemistry and analytical chemistry).

D.The course structure also includes practical training in the pharmaceutical industry. This
helps the candidates to prepare themselves for entering into actual working environment and
thus developing a successful career for themselves in the field.

Scope

A. Candidates with B.Pharm degree re eligible for serving in industries areas like
production, quality control, marketing etc., in pharmaceutical companies .

B.They can also get appointed to drug regulatory agencies or quality control laboratories by
the Central or state government.

C.They can also work in hospital or community pharmacy.

Master of Pharmacy (M.Pharm)

A.M.Pharm is a two year course after completion of B.Pharm regulated by AICIE.

B.Admission into M.Pharm is provided on the basis of academic performance in B.Pharm or

an entrance test or both. An essential criterion Graduate Pharmacy Aptitude Test (GPAT)
score qualifies students for stipend (government scholarship) during their study period.
However this criterion is optional for entry into the first year M.Pharm program.
C.This course is offered in many disciplines and students need to select any one
specialization of their interest.

D.Curriculum includes one year of study of various aspects in both theory and practical’s
followed by one year of research project under the supervision of an expert.

Scope

A.A pharmacist with M.Pharm degree is eligible to join pharmaceutical industries and choose
positions in areas such as research, formulation and development, clinical trials and
Pharmacovigilance. M.Pharm candidates are preferred over pharmacy graduates in R & D.

B.They can also work in academics as researchers or faculty members.

Pharm.D

A.It is a six years course after 10+2 or D.Pharmcy or three years course after B.Pharm (called
Pharm D post Baccalaureate).

B.It is regulated by PCI

C.Entry into this course is provided on the basis of academic performance in higher
secondary examination or D.Pharm program. B.Pharm degree holder can join in the fourth
year.

D. Curriculum comprises of 5 years of study (Theory and Practical) plus 1 year of internship
and residency at a practice site.

E.The syllabus is globally standardized and lays emphasis on Pharmacotherapeutics, clinical

research, community pharmacy, clinical toxicology, hospital pharmacy etc.

Scope

Pharm D degree holders are to work in academics, Hospital and R&D section of
pharmaceutical industries.
Regulation
In India, pharmacy education has dual control i.e. by the Central Council or Pharmacy
Council of India (PCI) and the All India Council tor Technical education (AICTE) for
maintaining the academic standards. ‘The Central Council provides complete details of the
course. Any institution or authority in India, conducting study courses for pharmacists must
apply to the Central Council for approval of the courses and examination. Following the
request, the Council deputes an inspection team to vist the institution and ascertains whether
the institution has minimum facilities and requirements for running the course and holding
examinations according to the education regulation of the Council. 'The inspectors the
authority to attend any examinations without interfering with its conduct to judge its
standards.

After thorough inspection the team prepares a report and submits the same along with
recommendations and remarks to the Central Council. Based on which the Council may or
may not grant to a course or examination. This approval is important to qualify for
registration as a pharmacist under the Pharmacy Act. Since pharmacy education also falls
under technical education. According to the AICI'E Act, any authority or institution
conducting pharmacy course should also undergo inspection by the team deputed by AICTE.
After submission of the inspection report. The expert committee assesses and evaluates the
facilities for starting a new course in pharmacy. Continuance of the existing courses, fix
norms and charges for the tuition and other fees. Lays down norms and standards for staff
qualification and increase in intake capacity etc.
Pharmacy Education-Future Prospects
The origin and development of pharmacy education in India over the past 150 years in
indicate of continuous change with the times.

Nevertheless, pharmacy education has to keep pace with emerging scenario as there has been
tremendous change in the number of drugs prescribed, method of Introduction to Dispensing
and General Pharmacy manufacturing. Introduction of computers in drug designing and
current emphasis on the development of novel drug delivery systems, Moreover in many
countries around the world. The practice of pharmacy has changed with emphasis shifting
from the product to the patient. To keep in tune with the current developments around the
globe. It is very important that the pharmacy education In India be restructured soon to take
into account the change in emphasis from Industrial pharmacy to professional pharmacy
settings. This can be achieved by encouraging the affiliation of pharmacy institutions the
teaching hospitals to provide the required clinical setting. Overall the whole, the future of
pharmacy education continues to look very bright, as it provides motivated professionals
with relevant knowledge, skills and job opportunities.Personal and professional satisfaction
in the service of community.
History of Ayurveda
The Origins
►The word ‘veda’ means knowledge.
►The evolution of the Indian art of healing and living a healthy life comes from the four
Vedas namely : Rig veda , Sama veda , Yajur veda and Atharva veda .
►Ayurveda attained a state of reverence and is classified as one of the Upa- Vedas - a
subsection - attached to the Atharva Veda.
►The Atharva Veda contains not only the magic spells and the occult sciences but also the
Ayurveda that deals with the diseases, injuries, fertility, sanity and health.
►Ayurveda incorporates all forms of lifestyle in therapy.
►Thus yoga, aroma, meditation, gems, amulets, herbs, diet, astrology, color and surgery etc.
are used in a comprehensive manner in treating patients.
►Treating important and sensitive spots on the body called Marmas is described in Ayurveda
Massages, exercises and yoga are recommended.

History

►The knowledge we have now is by three surviving texts of Charaka, Sushruta and
Vaghbata.

►Charaka (1st century A.D.) wrote Charaka Samhita (samhita- meaning collection of verses
written in Sanskrit).

►Sushruta (4th century A.D.) wrote his Samhita i.e Sushruta Samhita.

►Vaghbata (5th century A.D.) compiled the third set of major texts called Ashtanga Hridaya
and Ashtanga Sangraha.
►Charaka’s School of Physicians and Sushruta’s School of Surgeons became the basis of
Ayurveda and helped organize and systematically classify into branches of medicine and
surgery.
►Sixteen major supplements (Nighantus) were written in the ensuing years – Dhanvantari
Bahavaprakasha, Raja and Shaligrama to name a few – that helped refine the practice of
Ayurveda.
►New drugs were added and ineffective ones were discarded.
►Expansion of application, identification of new illnesses and finding substitute treatments
seemed to have been an evolving process.
►Close to 2000 plants that were used in healing diseases and abating symptoms were
identified in these supplements.
►Dridhabala in the 4th century revised the Charaka Samhita.
►The texts of Sushruta Samhita were revised and supplemented by Nagarjuna
in the 6th century.
►There developed eight branches/divisions of Ayurveda:
1.Kaya-chikitsa (Internal Medicine)

2.Shalakya Tantra (surgery and treatment of head and neck, Ophthalmology

 and ear, nose, throat)

3.Shalya Tantra (Surgery)

4.Agada Tantra (Toxicology)

5.Bhuta Vidya (Psychiatry)

6.Kaumara bhritya (Pediatrics)

7.Rasayana (science of rejuvenation or anti-ageing)

8.Vajikarana (the science of fertility and aphrodisiac)

►Many modern medications were derived from plants alluded to in Ayurveda texts.
►The oft-cited example is that of Rauwolfia serpentina that was used to treat headache,
anxiety and snakebite. Its derivative is used in treating blood pressure today.
►Two areas of contribution of Indian physicians were in treating snakebite and prevention of
small pox.
►Detailed account of steps to be followed after a poisonous snake bite including application
of tourniquet and lancing the site by connecting the two fang marks and sucking the poison
out is described.
►A decoction of the medicinal plant Rauwolfia serpentina is next applied to the wound.
►A form of vaccination for small pox was commonly practiced in India long before the West
discovered the method.
►A small dose of pus from the pustule of small pox lesion was inoculated to develop
resistance.

Charaka Samhita

►Charaka was said to have been in the court of the Kushana king, Kanishka during the 1st
century A. D.
►Some authors date him as far back as the 6th century B.C. during Buddha period.
►The sacred trust between physician and patient was held in high esteem by Charaka and
patient confidentiality, similar to the Hippocratic Oath, was deemed the proper conduct for a
practicing physician.
►Charaka also told us that the word Ayurveda was derived from Ayus, meaning life and
Veda meaning knowledge. Nevertheless, according to Charaka the word Ayus denotes more
than just life. Ayus denotes a combination of the body, sense organs, mind and soul.
►The principles of treatment in Charaka’s teachings took a holistic approach that treated not
just the symptoms of the disease but the body, mind and soul as single entity.
►Compiled by Charaka in the form of discussions and symposiums held by many scholars,
Charaka Samhita is the most ancient and authoritative text that has survived.
►Written in Sanskrit in verse form, it has 8400 metrical verses.
►The Samhita deals mainly with the diagnosis and treatment of disease process through
internal and external application of medicine called Kaya-chikitsa (internal medicine), it aims
at treating both the body and the spirit and to strike a balance between the two. Following
diagnosis, a series of methods to purify both the body and spirit with purgation and
detoxification, bloodletting and emesis as well as enema (known as Pancha-karma) are
utilized.
►The emphasis seems to be to tackle diseases in the early phase or in a preventative manner
before the first symptoms appear.
►Ayurvedic diagnosis and treatment is traditionally divided into eight branches (sthanas)
based on the approach of a physician towards a disease process. Charaka described them
thus:
1. Sutra-sthana - generalprinciples
2. Nidana-sthana - pathology
3. Vimana-sthan- diagnostics
4. Sharira-sthana - physiology and anatomy
5. Indriya-sthana - prognosis
6. Chikitsa-sthana - therapeutics
7. Kalpa-sthana - pharmaceutics
8. Siddhi-sthana - successful treatment.
►Detailed accounts of various methods of diagnosis, study of various stages of symptoms
and the comprehensive management and treatment of debilitating diseases like diabetes
mellitus, tuberculosis, asthma and arthritic conditions are to be found in the Charaka Samhita.
►There is even a detailed account of fetal development in the mother’s womb, which can
rival descriptions of modern medical textbooks.
►Charaka also wrote details about building a hospital.
►A good hospital should be located in a breezy spot free of smoke and objectionable smells
and noises. Even the equipment needed including the brooms and brushes are detailed.
►The personnel should be clean and well behaved.
►Details about the rooms, cooking area and the privies are given.
►Conversation, recitations and entertainment of the patient were encouraged and said to aid
in healing the ailing patient.

SushrutaSamhita

►Sushruta was a surgeon in the Gupta courts in the 4th century A.D.
►Though Indian classics is full of accounts of healing through transplantation of head and
limbs as well as eye balls, Sushruta Samhita is the first authentic text to describe
methodology of plastic surgery, cosmetic and prosthetic surgery, Cesarean section and setting
of compound fractures.
►Sushruta had in his possession an armamentarium of 125 surgical instruments made of
stone, metal and wood. Forceps, scalpels, trocars, catheters, syringes, saws, needles and
scissors were all available to the surgeon.
►Rhinoplasty (plastic surgery of the nose) was first presented to the world medical
community by Sushruta in his Samhita, where a detailed method of transposition of a
forehead flap to reconstruct a severed nose is given.
►Severed noses were common form of punishment. Torn ear lobes also were common due to
heavy jewelry worn on ear lobes. Sushruta described a method of repair of the torn ear lobes.
Fitting of prosthetics for severed limbs were also commonly performed feats.
►Sushruta wrote, “Only the union of medicine and surgery constitutes the complete doctor
►The doctor who lacks knowledge of one of these branches is like a bird with only one
wing.” While Charaka concentrated on the kaya-chikitsa (internal medicine).
►Sushruta’s work mainly expounded on the Shalya Tantra (surgery).
►The Samhita contains mostly poetry verses but also has some details in prose.
►72 different ophthalmic diseases and their treatment are mentioned in great detail.
►Pterygium(A pterygium is a growth of the conjunctiva or mucous membrane that covers the
white part of your eye over the cornea. The cornea is the clear front covering of the eye.
►This benign or noncancerous growth is often shaped like a wedge.), glaucoma and
treatment of conjunctivitis were well known to Sushruta.
►Removal of cataract by a method called couching, wherein the opaque lens is pushed to a
side to improve vision was practiced routinely.
►Techniques of suturing and many varieties of bandaging, puncturing and probing, drainage
and extraction are detailed in the manuscript.

Ashtanga Hridaya

►Vaghbata in the 5th century compiled two sets of texts called Ashtanga Sangraha and
Ashtanga Hridaya.
►It details the Kaya-chikitsa of Charaka Samhita and the various surgical procedures of
Sushruta Samhita.
►The emphasis seems to be more on the physiological rather than the spiritual aspects of the
disease processes.
►Ashtanga Sangraha is written in prose whereas the Ashtanga Hridaya is in poetry for
recitation of the Verses.

The Ancient ayurvedic Physician

►Originally only Brahmins ( a certain caste ) were practicing physicians.

►Later people from other castes became well versed in the art of healing and a term Vaidya
came to be applied to the practitioners.
►Merely by their art and knowledge, the physicians gained high social status regardless of
their caste of birth.
T►he court physician was of political importance and sat on the right side of the throne, an
important symbolic place.
►Though the physician, patient, the nurse and the medicine were all important in curing a
disease, the physician was thought to be the most important.
►The codes of conduct for physicians and medical students were laid down by the texts.
The poor and downtrodden were to be treated free of charge.
►Others were charged according to their ability to pay.
►The physician was expected to behave in an exemplary manner, conforming to the highest
ideals of professional and personal life.
►His dress, manner and speech were expected to be beyond reproach. Medical education was
arduous, consisting of many years of sacrifice learning the art of healing.
►Visiting the sick, collecting herbs and preparation of drugs, memorizing the Vedic texts of
Ayurveda,
►Performing procedures on dead animals, melons, and leather bottles and bladders were part
of the training.
►These exercises helped refine both theoretical and practical training of the student.
When finally the student is deemed ready to practice on his own, he was certified by the
ruler.

Recent History
►Before Ayurveda began its recent renewal in the West, it went through a period of decline
in India when Western medical education became dominant during the era of British rule.
►Ayurveda became a second-class option used primarily by traditional spiritual practitioners
and the poor.
►After India gained its independence in 1947, Ayurveda gained ground and new schools
began to be established.
►Today more than five hundred Ayurvedic companies and hospitals have opened in the last
ten years, and several hundred schools have been established.
►Although Ayurveda remains a secondary system of health care in India, the trend toward
complementary care is emerging, and Western and Ayurvedic physicians often work side by
side.
►Interest in Ayurveda in the West began in the mid 1970's as Ayurvedic teachers from
India began visiting the United States and Europe.
►By sharing their knowledge they have inspired a vast movement toward body-mind-spirit
medicine.
►Today Ayurvedic colleges are opening throughout Europe, Australia, and the United
States.
PHARMACY AS A CARRER

Pharmacists work in five areas:

1.Pharmacist in relation to his profession

2.Pharmacist In Relation To Medical Profession

3.Pharmacist in relation to his job (Retail or Community pharmacist)

4.Pharmacist In Relation To His Trade (Manufacturing pharmacist)

5.Ethical issues in research(Research Pharmacist)

1.Pharmacist in relation to his profession

1.A pharmacist should observe the law and ethical principles to maintain the standard of the
profession.

2.A pharmacist should extend the help and co-operation to his fellow pharmacist in an
emergency legitimate(regular) need.

3. A pharmacist should try to weed (wild plant growing where it is not required ) out the
undesirable corrupt or dishonest conduct of the member of his profession maintaining its
status in society.

4.A pharmacist should have a fair knowledge of laws of the state and nation
pertaining(belonging) to food, drug, pharmacy education, health etc.

5.A pharmacist should have upto date knowledge of professional matters. He should associate
himself with various pharmaceutical organizations, the aims and objects of which are
compatible with this code of ethics.

6.A pharmacist should not perform such acts which will bring discredit to his profession or to
himself.

2.Pharmacist In Relation To Medical Profession

1.A pharmacist, under no circumstances, should practice medicine, that is diagnosing

diseases and prescribing medicines. However, in case of accidents or emergencies, he may
render first aid services.

2.A pharmacist should not recommend any particular medical practitioner, unless specially
asked for.

3.Pharmacist should never enter in to any secrete agreements with the medical profession,
physicians, dentist, veterinary surgeons to offer them commission or gifts by recommending
his dispensary or drug store.
4.Pharmacist is a link between medical profession and public. He should be constantly in
touch with modern development in pharmacy and allied fields. He should be expert in the
field of pharmacy so that he may advice the physicians on pharmaceutical matters. By
enlarging his store of knowledge he may be able to educate the public to maintain their
health.

5.Pharmacists should neither discus physician’s prescriptions with customers nor disclose to
them the composition of prescriptions.

3.Pharmacist in relation to his job (Retail or Community pharmacist)

Pharmaceutical services:

1. A pharmacist should provide efficient and reasonably comprehensive pharmaceutical

services through the medical store or pharmacy.
2. Such services include supply of commonly required medicines without delay and
furnishing the emergency supply at all times.
Pharmacy / drug store

3. In every pharmacy/drug store, there should be a qualified pharmacist to have personal

control over the pharmacy. The pharmacist shall be primarily responsible for the
observance of proper standards of conduct in connection with it.
4. A pharmacy should be planned in such a way that there is no accidental contamination
in the preparation, dispensing and supply of medicines.
5. The appearance of the premises should reflect the professional character of pharmacy
and indicate to the public that the practice of pharmacy is the main purpose of the
establishment.
Prescriptions

6. Prescriptions presented for dispensing should not be discussed with patients or others
regarding the merits and demerits of their therapeutic efficiency.
7. After receiving the Prescriptions, a pharmacist should not even show any expression
on his face so that the patients will lose their faith in the physicians or prescribers.
8. No, addition, omission, or substitution of ingredients in a prescription should be made
without the consent of prescriber or physician whenever possible except in an
emergency.
9. In case of any obvious error in the Prescription, it should be referred back to the
prescriber for necessary correction or approval of the change suggested.
10. If at all the change in the Prescription is necessary in the interest of health of patient,
it should not affect the reputation of the physician or prescriber.
11. A pharmacist should not recommend any particular prescriber unless he is specially
asked to do so.
Drugs/ ingredients

12. While dispensing the Prescription, the ingredients or drugs must be weighed or
measured correctly as the case may be by scales or measures.
13. Pharmacist should always use drugs and medicinal preparations of standard quality.
 14. Drugs or medicine likely to cause addiction or other form of abuse should not be
supplied when there is reason to suppose that it is required for such purpose.
Practical training

15. While imparting practical training the in charge pharmacist should see that the
trainees acquire sufficient technique and skill.
16. No certificate should be granted to the trainee pharmacist before completion of
prescribed period for training or without undergoing practical training or unless the
trainee acquires sufficient knowledge.
4.Pharmacist In Relation To His Trade (Manufacturing pharmacist)

Price structure

1. Prices of drugs and medical preparations charged from the customer should be fair
and including dispensing and compounding charges without taxing the purchaser.
Fair trade practice

2. A pharmacist should not make any attempt to capture the business of follow
pharmacist by unhealthy competition or cut-throat competitions that is by offering
reduced price, gifts, prizes etc.
3. Trademarks, labels, symbols or nay other signs of other pharmacists should not be
copied.
4. Drugs or other ingredients required should always be purchased from reputable
sources.
Hawking (Selling of goods on road) of drugs and other:

5. Hawking of drugs and medicines should not be practiced and any attempt should not
be made to collect the orders from door to door.
6. Self servicing method in the pharmacy or drug stores should not be allowed as it
would encourage self medication which is undesirable and dangerous.
Advertisement and display

7. There should not be any display or advertisement on the premises, in the news paper
or elsewhere regarding the abilities and services provided by the pharmacy.

The pharmacist should not make such advertisements which contain:

a. Misleading or exaggerated statements or claims.
b. A guarantee of therapeutic efficacy.
c. An offer to refund money paid.
d. An appeal to fear.
e. The word ‘cure’ in reference to an ailment or symptoms of ill-health.
5. Ethical issues in research (Research Pharmacist)

►Good Research Practice (GRP) should ensure that research is well-planned, appropriately
designed and ethically approved.
►The requirement of ethics committee approval is a stringent(rules) requirement for medical
related research where there may be use of animal or human subjects.

►Approval is needed from the institutional review board (IRB) or institutional ethics
committee (IEC) of the respective establishment on research involving humans or human
tissues, medical records or surveys of certain research issues.

►In the US, an IRB is a board, a committee or a group of people formally designated by an
institution like hospitals, academic medical centers, government units and others engaged in
conducted or supported health research activities involving human subjects to review
research involving humans as subjects.

►An IRB has the authority to approve modify or disapprove related research activities.
Upon approval, IRBs must conduct periodic reviews of such research.

►In the US all IRB must have not less than five members with varying backgrounds and
each member must be sufficiently qualified through the experience and area of expertise.

►The membership should also be as diverse as possible in term of race, gender and cultural
backgrounds.

►IRB should not include member who has conflict(fight) interest, except on special cases
where needed.

►All IRBs must include at least one member who are in scientific areas and at least one
member who are in nonscientific areas.

►Some nation do not have IRB but instate they have institutional ethics committee (IEC)
with similar set up of members and function as an IRB.

►Drug development research is one of the main activities of a pharmaceutical company

involved in research.

Modern drug development follows the following key stages:

Program selection (choosing the disease target), identification and validation of the drug
target, assay development, identification of a lead compound, optimization of the lead
compound, identification of a drug candidate, preclinical study (a broad study encompassing
animal studies, toxicity studies and pre-formulation studies), clinical trials on human subjects,
registration and release of the drug to the market and follow-up monitoring (adverse drug
reaction reporting).

Generally, pharmaceutical companies will invest more on research for drugs which are likely
to be more lucrative (Profitable) in their sales. Usually those diseases suffered by people in
developed nations will be more attractive for the pharmaceutical companies. For example, not
much research is being carried out by pharmaceutical companies on drugs for AIDS as the
vast majority of AIDS sufferers are from the third world such as those from the African
continent. Ethically this is not right but the pharmaceutical companies need to pay back the
money which has been spent on research.
 PHARMACOPOEIA /FORMULARIES /COMPENDIA
►The books containing the standards for drugs and other related substances are known
as Pharmacopoeia and formularies - collectively these books are known as the drug
compendia.

►The pharmacopoeias or formularies contain a list of drugs and other related substances
regarding their source, descriptions, standards, tests, formulae for preparing the same, action
and uses, doses, storage conditions etc.

►These books are prepared under the authority of the Government of the respective
countries.

►The word “Pharmacopoeia” is derived from the Greek words ‘pharmacon’ meaning ‘drug’
and ‘poeio’ means ‘make’. Literally it means that it is a list of medicinal substances, crude
drugs and formulae for making preparations from them.

►These books are revised from time to time so as to introduce the latest information
available as early as possible after they become established.

►In order to keep the size of book within reasonable limit it becomes necessary to omit
certain less frequently used drugs and pharmaceutical adjuvants from each new edition of the
book. Therefore, in each new edition of these books certain new monographs are added while
the older ones are deleted. For the preparation of these books the expert opinion of medical
practitioners, teachers and pharmaceutical manufacturers are obtained.

CLASSIFICATION

The drug-compendia are classified as:

A. Official compendia

B. Non-official compendia

A. Official compendia

Official compendia are the compilations of drugs and other related substances which are
recognized as legal standards of purity, quality and strength by a government agency of
respective countries of their origin.

e.g. British Pharmacopoeia (BP)

British Pharmaceutical Codex (BPC)

Indian Pharmacopoeia (IP)

United States Pharmacopoeia (USP)

National Formulary (NF)

 The State Pharmacopoeias and Pharmacopoeias of other countries.

B. Non-official compendia

The book other than official drug compendia which are used as secondary reference sources
for drugs and other related substances are known as non-official drug compendia. e.g.
Merck Index

Extra Pharmacopoeia (Martindale)

United States Dispensatory etc.

INDIAN PHARMACOPOEIA

History

►The historical developments of Pharmacopoeia in India traces back to 1563 and the credit
go to Garcia da Orta a Portugese physician-cum-teacher.

►The idea of indigenous Indian Pharmacopoeia was conceived in 1837 which bore fruits in
1841 in the shape of Bengal Pharmacopoeia and Conspectus of Drugs.

►The Bengali and Hindi version of London Pharmacopoeia was made available in India
from 1901 onwards.

►The Indian Pharmacopoeial List, published in 1946 formed the seeding for the true Official
Indian Pharmacopoeia published in 1955.

►The first edition of Indian Pharmacopoeia was published in 1955, but actually the process
was started as early as 1944.

►In 1944 Government of India asked the Drugs Technical Advisory Board to prepare the list
of drugs used, in India, having sufficient medicinal value to justify their inclusion in official
pharmacopoeia.

The Indian Pharmacopoeial List, 1946.

►The list of drugs both included and not included in the British Pharmacopoeia along with
standards to secure their usefulness, tests for identity and purity was prepared by the
committee and was published by the Government of India under the name ‘The Indian
Pharmacopoeial List 1946’.The committee constituted under the chairmanship of Col. Sir
R.N.Chopra along with other nine members prepared the list of drugs with the following
details:

►Substances included in the British Pharmacopoeia for crude drugs, chemicals and their
preparations.

Substances not included in the British pharmacopoeia

a) Drugs of plant origin

b) Drugs of animal origin

c) Biological products

d) Insecticides

e) Colouring agents

f) Synthetics

g) Miscellaneous

h) Drugs for veterinary use.

The Indian Pharmacopoeia list 1946 was prepared by Department of Health, Govt. of India in
1946.

The history of development of Indian Pharmacopoeia:

YEAR EVENTS
1946 The Govt. of India published the Indian Pharmacopoeial List.
1948 The Govt. of India constituted a permanent Indian Pharmacopoeia Committee.
This committee was assigned the task of preparing Indian Pharmacopoeia and to
keep it up-to-date.
1955 The first edition of Indian Pharmacopoeia (IP) was published.
1960* Supplement of IP 1955 was published.
The work of revision of the Indian Pharmacopoeia as well as compilation of new
edition was taken up simultaneously under the chairmanship of Dr. B.N.Ghosh,
who died in 1958. After Dr. B.N.Ghosh, Dr. B.Mukherjee, the Director of Central
Drug Research Institute was appointed as the chairman of Indian Pharmacopoeia
committee.
1966** The second edition of IP was published.
1975 A supplement of IP 1966 was published.
1978 The Indian Pharmacopoeia Committee was reconstituted by the Govt. of India,
Ministry of Health and Family Welfare, under the chairmanship of Dr. Nitya
Nand, Director, Central Drug Research Institute, Lucknow.
1985 The third edition of IP was published in two volumes, Volume-I and Volume-II by
the Controller of Publications, on behalf of Govt. of India, Ministry of Health and
Family Welfare.
1991 Addendum (I) to IP 1985 was published.
Addendum (II) to IP 1985 was published.
1996* The fourth edition of IP was published.
Volume-I contains:
Legal Notices, Preface, Acknowledgments, Introduction, General Notices, and
Monographs from A to O.
Volume-II contains:
Monographs from P to Z, Appendices, Contents of Appendices and Index.
Th The Appendices includes the:
i.Infra Red Spectra of drugs,
ii. Apparatus for tests and assays
iii. biological tests and determinations,
 iv.chemical tests and assays,
v. chromatography and electrophoresis
vi.Spectrophotometry
vii.Clarity and color of solutions
viii.Disintegration and dissolution tests
ix.Physical tests and determinations
x.microbiological assays and tests,
xi.limit tests of particulate matter
xii.other tests and determinations
xiii.general information
xiv.reagents and solutions
xv.reference substances
xvi. tables
Index
Under each monograph chemical structures, molecular weight, physical
description, solubility, identification tests, standards, assay method, storage etc. is
given.
2007 The fifth edition of IP was published.
2010 The sixth edition of IP was published.
2014 The seventh edition of IP was published.
2018 The Eighth edition of IP was published.
Published by: The Controller of Publications, Delhi, on behalf of Government of India,
Ministry of Health and Family Welfare.

►For the preparation of Pharmacopoeia of India, the pharmacopoeias of other countries, like
British, Europe, United States, USSR, Japan, the National Formulary (USA) and Merck
Index were consulted. The persons working in pharmaceutical industry, drug control
laboratories, research and teaching institutions also actively participated.

►Under the Drugs and Cosmetics Act 1940, the Indian Pharmacopoeia is an official book that
contains the standards for drugs and other related substances included in the pharmacopoeia.
The drugs and other related substances prepared by pharmaceutical manufacturers must
comply with these standards.

EXAMPLE OF A MONOGRAPH OF AN OFFICIAL DRUG

The word ‘Monograph’ means the written study of a subject. The pharmacopoeial
monographs (for example in IP) give the following information about the drugs and
pharmaceutical aids:-

1.Main title: The main name of the substance.

2.Synonym: The common name(s), if any, of the substance.

3.Chemical formula and Molecular Weight of the substance: If necessary, its I.U.P.A.C.
chemical name and/or its chemical structure is also given.

4.Category: Indicates the use of the drug in medicine and pharmaceutical practices. e.g.
Antibacterial, antimalarial, diuretic, emetic, expectorant etc.
 5.Doses: Represents the average range of quantities suitable for adults.

6.Description: This includes the general physical properties, i.e. whether the substance is a
solid or liquid, colourless or coloured, crystalline or amorphous, its taste etc.

7.Solubility: According to IP the solubilities of the substances are mentioned in terms of

descriptive phrases as follows:

Descriptive phrase Volume of solvent for dissolving 1 part of solute.

Very soluble Less than 1 part
Freely soluble 1 to 10parts
Soluble 10 to 30 parts
Sparingly soluble 30 to 100 parts
Slightly soluble 100 to 1000 parts
Very slightly soluble 1000 to 10,000 parts
Practically insoluble / more than 10,000 parts
insoluble
8. Standards: Prescribes the standards of purity and strength e.g. Sodium bicarbonate IP
contains not less than 99.0 % and not more than 100.5 % of NaHCO3.

9. Identification: This includes some specific and some non-specific tests for identity of
substance.

10.Tests of purity: These tests include melting point, boiling point, weight per ml, limit tests
for chloride, sulfates, iron, heavy metals, lead and arsenic, specific optical rotation, sulfated
ash, loss on drying, pH of solution, etc. as may be applicable for the substance.

11.Method of Assay: The term ‘Assay’ is used in pharmacopoeias for quantitative

determination of principal ingredients of the official substances and of their preparations.

12. Storage: Prescribes some conditions for the storage of some official substances which are
likely to deteriorate if not properly stored.

Salient Features of the First Edition of Pharmacopoeia of India (1955)

1. The title of monographs has been given in Latin language abbreviated titles for use in
prescription has been given immediately below the Latin title.

2. The English title has also been given below the abbreviation title.

3. The weight and measures have been given in metric system.

4. All statements contained in the individual monographs have been considered as constitute
standards for the official substances.

5. Doses are expressed both in the metric system as well as in the English system.

6. A list of preparations has been given at the end of some of the monographs.

7. The temperature has been given at the end of some of the monographs.
8. The descriptive terms (very soluble, freely soluble, sparingly soluble, slightly soluble very
slightly soluble, practically insoluble) have been used where the exact solubility of a
pharmacopoeial substance is not known.

The tenure of the first Indian pharmacopoeial committee expired in 1954, and the
Committee was reconstituted under the chairmanship of Dr.B.N.Ghosh, professor of
Pharmacology, R.G.Kar Medical College, Kolkata. The Committee compiled a supplement
was published in 1960. The composition of the Committee entrusted with the compilation of
the second edition of Pharmacopoeia was as follows:

1. Chairman

2. Members—11 in number

3. Member-Secretary

4. Assistant- Secretary

The Committee appointed the following Subcommittees to assist it in the compilation work:

1. Pharmacology & Bioassay Subcommittee

2. Biological Product Subcommittee

3. Antibiotics, Vitamin & Hormones Subcommittee

4. Pharmacognosy Subcommittee

5. Pharmacy Subcommittee

6. Pharmaceutical Subcommittee

7. General Chemistry Subcommittee

8. Analytical Subcommittee

9. Physical Standard, Weights, Measures and Nomenclature Subcommittee

10. Indian Medicinal Plants Subcommittee

A Coordination Subcommittee consisting of the Chairman and Secretary of the Indian

pharmacopoeia committee and the Chairman of the various Subcommittees was also
constituted to coordinate the work of various Subcommittees.

In order to expedite the compilation of the second edition of pharmacopoeia, the Indian
Pharmacopoeia Committee constituted a “Working Group” to examine the comments
received on the draft monographs and then submitted suitable recommendations to the
Committee in the light of their comments. The second edition of the Pharmacopoeia of India
was published in 1966 and later on its supplement was published in 1975.
Salient Features of the second Edition of Pharmacopeia of India (1966)

1. The title of monographs have been changed from Latin English.

2. The words of the title have been transposed to give the name of the drug first e.g. Injection
of, Aminophylline Injection.

3. Doses are expressed in the metric system only.

4. Solubility is expressed in parts of solvent per unit of solute.

5. The preparation of a drug have been given immediately after the monograph on the parent
drug.

6. The test for sterility has been modified to provide for detection of fungi in addition to
aerobic and anaerobic bacteria.

7. New analytical techniques such as non-aqueous titrimetry, column chromatography have

been included.

8. In the monographs of “Tablets” and “Injections”, a new subheading “Usual Strength” has
been given to represent strength of the tablet or injection in which it should be generally
marketed.

The government of India, Ministry of Health and Family Welfare, wide their resolution
No.X19014/1/77-D& M.S., dated 30th June 1979, reconstituted the Indian pharmacopoeia
committee for a period of five years for the preparation of the third edition of Pharmacopoeia
of India. The composition of the committee was as follows:

1. Chairman

2. Members—13 in number representing academic, research and industry

3. Member-Secretary

4. Assistant- Secretary

The committee appointed the following subcommittees:

1. Clinical Medicines &Pharmacology Subcommittee

2. Biological Products & Bioassay Subcommittee

3. Antibiotics Subcommittee

4. Synthetic Drugs Subcommittee

5. Medicinal Plants, Galenicals & Surgical- Dressings Subcommittee

6. Chemicals & Pharmaceutical Aids Subcommittee

 7. Parenteral & Sterile Product Subcommittee

8. Non Parenteral Product Subcommittee

9. Analytical Methods, Reagents, Diagnostic Aids & Containers

Subcommittee

10. Nomenclature & Formulae Subcommittee

The Indian Pharmacopoeia Committee also constituted a “Working Group” for the
purpose of preparation draft monographs and appendices, to examine the comments received
on these from various sources and then make suitable recommendation to the Committee.

The Monographs, Appendices and General Notes as prepared by the “Working Groups”
and finalised by the committee were then published in the form of third edition of the
pharmacopoeia of India in 1985 by the Government of India.

Salient Features of the Third Edition of Pharmacopeia of India (1985)

1.The new analytical techniques such as flame photometry, Flurometry, Electrophorosis and
photometric Haemoglobinometry have been introduced as official method for certain
chemical analysis.

2. Dissolution Test has been introduced in the case of certain tablets.

3. Disintegration Test has been amended by modifying the design of the apparatus and
method of testing.

4. A microbial limit test has been prescribed for certain pharmaceutical aids and oral liquid
preparations.

5. The pyrogen Test has been revised to make the test less time-consuming than the previous
method.

6. Gas Liquid Chromatography has been recognised as an alternative method for the
determination of alcohol concentration in various preparations.

7. The test for determination of viscosity has been modified by the introduction of other
methods involving the use of Ostwald Viscometer.

8. The new appendix on” Water for Pharmaceutical Use” has been introduced to clearly
indicate the different official standard in respect of purified water, water for injection and
sterile water for injection.

9. Some of the drugs have been renamed in this edition e.g. ‘Acetylsalicylic Acid’ has been
changed to ‘Aspirin’.

10. Many drugs have been omitted from the third edition and many new drugs have been
included in the third edition.
 The Government of India, Ministry of Health and Family Welfare vide their resolution
No. X19020/1/89-DMS and PFS dated 12th August 1991, reconstituted the Indian
Pharmacopoeia Committee for a period of five years for the preparation of the fourth edition
of Pharmacopoeia of India. The composition of the committee was as follows:

1. Chairman

2. Members—18 in number representing academic, research and industry

3. Member-Secretary

4. Assistant- Secretary

The Committee appointed the Subcommittees and working groups in order to expedite
the preparation of the new edition of the Indian Pharmacopoeia.

The Monographs, Appendices and General Notes as prepared by the “Working Group”
and finalized by the Committee were then published in the Pharmacopoeia of India in 1996
by the Government of India.

Salient Features of the Fourth Edition of Pharmacopeia of India (1996)

1. It contains 1149 monographs and 123 appendices and available in two volumes.

2. The computer-generated structural formulae have been introduced.

3. Some titles have been changed to include the more commonly accepted names in India.
E.g. Hyoscine Hydrobromide for Scopolamine Hydrobromide

4. Infra-red and ultra-red absorption spectrophotometric tests for identification of drug

substance have been introduced as alternative test tests to the classical chemical tests. The
infra-red reference spectra of a number of drug substances have been included in an
appendix.

5. The high performance liquid chromatography (HPLC) has been widely used as a method to
analyse many formulation which can otherwise be analysed only by more difficult and less
accurate method e.g. biological assay of Insulin has been replaced by HPLC.

6. The test for bacterial endotoxins as a more suitable substitute for the test for pyrogens has
been introduced for some articles.

7. A number of general monographs e.g. eye drops; eye ointment, nasal, preparations, oral
liquids, pessaries, suppositories etc. have been included.

8. A quantitative method for determinining particulate matter in injectable preparations has

been replaced by the qualitative test of the previous edition. The test is applicable to
injectable solutions that are supplied in containers with 100ml or more.

9. The specific biological assay and tests provided for vaccines; hormones, blood product and
enzymes have been transferred from an appendix to the individual monographs.
10. In the monographs for Oral Rehydration Salts (ORS), ORS-Bicarbonate formula has been
dropped due to its stability problem, whereas ORS-Citrate formula recommended by WHO is
retained.

After the publication of fourth edition of the Indian Pharmacopoeia in 1996, an addendum
was published in 2000. In view of rapid developments in the field of pharmaceutical sciences
and technology it becomes necessary to update the official compendium frequently.
Addendum 2002 was published to incorporate the latest developments made in
pharmaceutical sciences. The numbering of pages in this Addendum is continuous with that
Volume I and II of Indian Pharmacopoeia 1996 and Addendum 2000. The following changes
are made:

1. A number of tests and standards in monographs have been amended and replaced with old
monographs.

2. The test on bacterial endotoxins replaces the pyrogen test.

3. The new appendix on ’residual solvent’ has been incorporated to monitor the content of
organic volatile impurities that are used or produced in the manufacture of an active
pharmaceutical substance, excipient or medicinal product.

4. An appendix on HPLC has been replaced by a revised version covering ion

chromatography.

5. Monographs of a number of antiretroviral activities and their formulations have been

introduced in this Addendum.

6. Monographs on vaccines for Hepatitis B and that for Rabies have been revised.

Government of India has constituted the Indian Pharmacopoeia Commission (IPC) on 22nd
March 2005. The Commission has its headquarters at the Central Indian Pharmacopoeia
Laboratory (CIPL), Sector-23, Rajnagar , Ghaziabad U.P. The Indian Pharmacopoeia
Commission has a tree ties structure comprising of the General Body of 19 members,
Governing Body 8-10 members and Scientific Body of 15-23 members from different related
scientific fields. Various expert Committees were also made to prepare various monographs.

Salient Features of the fifth Edition of Pharmacopeia of India (2007)

1. The Indian Pharmacopoeia 2007 is presented in three volumes. Volume I contains the
general notes, preface, the structure of the IPC, Introduction and general chapters. Volume II
deals with the general monographs on drug substances, dosage forms, pharmaceutical aids,
vaccines, and immunosera for human use, herbal products, blood related fluids,
biotechnology products and veterinary products.

2. General chemical test for identification have been almost eliminated and more specific
infrared and ultraviolet spectrophotometric tests have been given.
 3. The test for pyrogens involving the use of animals have been virtually eliminated. The test
for bacterial endotoxins has been introduced.

4. The test for abnormal toxicity is now confined to certain vaccines.

5. The use of chromatographic methods has been extended in assays to large number of
pharmaceutical products.

6. Labelling and storage is featured at the end of a monograph.

7. The general monographs for dosage forms of active pharmaceutical ingredients are
grouped together at the beginning of volume II followed by the monographs for active
pharmaceutical ingredients, pharmaceutical aids and individual dosage forms, all in
alphabetical order.

8. Monographs for other articles of a special nature such as vaccines and immunosera for
human use, herbs and herbal products, blood and blood related products, and veterinary
products are given in separate in volume III.

9. Limit of bacterial contamination has been introduced for controlling the microbial quality
of all medicinal products.

10. Analytical methods are in general in harmony with those adopted internationally for
monitoring the quality of drugs.

Salient Features of the sixth Edition of Pharmacopeia of India(2010)

Specific
features
Adding:
(i) New monograps.
(ii) Category, Dose and Usual Strengths.
(iii) General Chapter on Liposomal Preparations.
(iv) Appendices on NMR.
(v) New Herbs and Herbal monographs.
(vi) Excipient monographs.
(vii) Anticancer monographs.
(viii) Adopted for latest drug delivery system (i.e. Amphotericin B Injection).
(ix) Drugs not in use are omitted from this edition.
►The scope of the Pharmacopoeia has been extended to include products of biotechnology,
indigenous herbs and herbal products, Veterinary vaccines and additional antiretroviral drugs
and formulations, inclusive of commonly used fixed dose combinations.
►Standards for new drugs and drugs used under National Health Programmes are added in
this edition and drugs as well as their formulations not in use now a days are omitted from
this edition.
►The number of monographs of Excipients, Anticancer drugs, Herbal products and Anti
HIV drugs have been increased in this edition.
►Monographs of Vaccines and Immunosera are also upgraded in view of latest technology
in the field.
►A new chapter on Liposomal products and a monograph of Liposomal Amphotericin B
injection is an added advantage in view of latest technology adopted for drug delivery.
►A chapter on NMR is also incorporated in Appendices.
►The chapter on microbial contamination is also updated to great extent to harmonize with
prevailing international scenario.
Salient Features of the seventh Edition of Pharmacopeia of India (2014)
►First time IP-2014 included with DVD-ROM

►Out of 577 New Monographs, 134 API monographs,161 formulations monographs, 18

excipient

Monographs, 43 NDS monographs, 10 antibioticmonographs, 19 anticancer monographs, 11

antiviralmonographs are included in this edition.

►Also 31 herbal monographs, 05 monographs on vaccine & immunosera for human use, 06
monographs

on insulin products and 07 monographs onbiotechnology products are included.

►19 new General Chapters and about 200 new IRspectra’s are also added.

►For the first time in IP, introducing 19 newRadiopharmaceutical Monographs with one
General

Chapter on Radiopharmaceutical preparations.

►This time separate volume of veterinary products isalso introduced for easy access.

►143 monographs on veterinary products along with16 appendices/General chapter on

veterinaryproducts are also introduced.

Now total number of IP Standards is reaching almost3000 which is almost at par with other
internationalPharmacopoeias and comprising different categories ofdrugs and appendices as
mentioned below:

IP-2014 : Total Standards

- General Monograph on Dosage Forms: 37

- Monographs on Drug Substances, Dosage forms and Pharmaceutical Aids (A to Z)

Total Monographs : 2585+82 = 2667

Appendices: 197

Total Standards: 2782+82 = 2864

►The Standards prescribed in the Indian Pharmacopoeia are to establish the compliance with
regulatory

requirements on an article. The criteria to be adhered toare:

(a) The interpretation of a monograph must be inaccordance with all the general
requirements, testing

methods, texts and notices pertaining to it, in the IP and.

(b) A product is not of standard quality unless itcomplies with all the requirements of
the monograph.

Salient Features of the eighth Edition of Pharmacopeia of India (2018)

General Chemical tests & Thin Layer Chromatography (TLC) for identification of an article
have been almost eliminated; and more specific infrared, ultraviolet spectrophotometer and
HPLC tests have been emphasized.

THE BRITISH PHARMACOPOEIA (BP)

History:

Published by: The British Pharmacopoeia Commission The Stationary Office.

Meant for: The pharmaceutical and chemical industries, quality control personnel, Analysts,
government regulators, academics and students of pharmacy.

1964: First edition of BP

1968: British Pharmacopoeia Committee was constituted.

1980: 13th Edition of BP was published

1988:14th Edition of BP was published. Contains two volumes with 2100 monographs.

1993: 15th Edition of BP was published.

1993: 15th Edition of BP was published.

1998: A consolidated edition as published.

Salient features of BP 1998

►Three volumes.

►All monographs of the European Pharmacopoeia (third edition) included

►Includes British Pharmacopoeia (Veterinary Medicine for separate volume)

►CD-ROM included in the package for easy search.

►Annual publication from 1998 onwards. In every year a new edition is published.
►Free access to Pharmacopoeia website

NATIONAL FORMULARY OF INDIA

►For the guidance of medical practitioners, medical students and pharmacists in hospitals
and in sales departments National Formulary of India has been formulated.

1960:First edition was published by Govt. of India, Ministry of Health.

1966: Second edition was published.

1979: Third edition was published.

It contains information about drug interactions, resistance, cumulative effects, drug

dependence, prescription writing etc.

BRITISH PHARMACEUTICAL CODEX (BPC)

It was in 1903 that the council of Pharmaceutical Society of Great Britain decided to
prepare a reference book for the use of medical practitioners and dispensing pharmacists. The
first edition of BPC was published in 1907.

On the request of British Pharmacopoeia Commission, the Council of the

Pharmaceutical Society agreed in 1959 for the publication of Codex to coincide with that of
the BP, so that BP and BPC should come into effect on the same date.

The BPC differs from BP in that:

a)It contains many more drugs and preparations some may be included in advance to the
pharmacopoeia while other drugs may have been included in the former editions of
pharmacopoeia but now they are retained in the Codex because they are still commonly used.

b) It provides information on the actions and uses of drugs, their undesirable effects,
precautions and the treatment of poisoning.

c) It contains formulae, method of preparation, container and storage conditions of most of

the preparations that are still extemporaneously prepared in the pharmacy.

THE UNITED STATES PHARMACOPOEIA (USP)

The USP was originally published in 1820 under the authority of United States
Pharmacopoeial Convention. The National Formulary (NF) was published in 1888 under the
guidance of American Pharmaceutical Association.

In 1974 the NF was purchased by the United States Pharmacopoeial Convention and from
1980 onwards only one official book of drug standards was published under the heading The
United States Pharmacopoeia and The National Formulary (USP-NF).
THE INTERNATIONAL PHARMACOPOEIA

►The International Pharmacopoeia is published by the World Health Organization and is

particularly used in developing countries. The object of this was to provide a uniform list
which would avoid the confusion caused by different national standards, strengths and names.

YEAR VOLUMES
1951 Volume-1 of First Edition of The International Pharmacopoeia was published.

1952 Volume-2 of First Edition of The International Pharmacopoeia was published.

1959 Supplement to First Edition was published

First Edition includes
344 monographs on drug substances
183 monographs on dosage forms (capsules, injections, tablets and tinctures)
84 tests, methods and general requirements.
1967 Second Edition of The International Pharmacopoeia was published
as Specification for the Quality Control of Pharmaceutical Preparations.
Second Edition includes
New analytical techniques involving infrared spectroscopy, chromatography
(column, paper and thin-layer), non-aqueous titration, and radioactivity.
162 new pharmaceutical preparations were added.
114 monographs present in the first edition were deleted.
1975 Volume-1 of Third Edition of The International Pharmacopoeia was published.
1981 Volume-2 of Third Edition of The International Pharmacopoeia was published.

1982 Volume-3 of Third Edition of The International Pharmacopoeia was published.

1988 Volume-4 of Third Edition of The International Pharmacopoeia was published.
2003 Volume-5 of Third Edition of The International Pharmacopoeia was published.

Salient features of Third edition

Emphasis on classical chemical techniques available in the developing world.

Drugs those are used all over the world by various WHO programs.

Drugs those degrade or are difficult to manufacture.

Drugs from WHO Model List of Essential Drugs, and their updates.

Volume-1:General methods of analysis

Volume-2 & 3:Quality specifications of essential drug substances in the WHO

Model List of Essential Drugs.

Volume-4: Tests, methods, and general requirements. Quality specifications for

pharmaceutical substances, excipients, and dosage forms.

Volume-5: Contains tests and general requirements for dosage forms and quality
 specifications for pharmaceutical substances and tablets on antimalarial drugs and their
most widely used dosage forms.

EXTRA PHARMACOPOEIA (MARTINDALE)

History: The Extra Pharmacopoeia was first produced in 1883 by William Martindale and is
still known as ‘Martindale’.

Produced by: The Royal Pharmaceutical Society of Great Britain

Meant for: Medical Practitioners and Pharmacists all over the world.

Sources of information: Journals and periodicals, licensed product literature, WHO

publications, government reports and legislation and other official and standard publications.

Contains information about: Drugs and medicines, selected investigational and veterinary
drugs, herbal medicines, pharmaceutical excipients, vitamins and nutritional agents, vaccines,
radiopharmaceuticals, contrast media and diagnostic agents, medicinal gases, drugs of abuse
and recreational drugs, toxic substances, disinfectants, and pesticides.

Monograph headings: Definitions and descriptions, pharmacokinetics, adverse effects and

treatments, uses, precautions, administration, interactions, tradenames of preparations.

Additional information: Disease treatment reviews that provide overviews of diseases and the
choice of treatments available.

Details of commercial preparations from a wide range of countries.

Directory of drug-manufacturers and their addresses worldwide.

THE MERCK INDEX

It is an encyclopedia of chemicals, drugs and biologicals. The first edition was published in
1889 and the eleventh edition was published in 1989 by Merck & Co., Inc. Rahway, New
Jersey and USA.
PRESCRIPTION
►A physician is written order from a registered medical practitioner or other properly
licensed practitioners such as dentist, veterian etc. to a Pharmacist to compound and dispense
a specific medication for the order is accompanied by direction for the pharmacist to prepare
a specific type and quantity of preparation for a patient.

►The prescription directs the patient about the mode of administration of drugs which is
dispensed for home.

►Thus prescription is a media through which treatment is provided for a patient by the
combined skill and services of both the physician and the pharmacist.

►The prescriptions are generally written in English language but Latin words or
abbreviations are frequently used in order to save time.

►So it becomes necessary for a pharmacist, to become familiar with the common Latin
terms and abbreviations used by the prescriber while writing the prescription.
PARTS OF PRESCRIPTION

►A complete prescription should have the following parts:

1. Date
2. Name, Age, Sex and Address of the Patient
3. Superscription
4. Inscription
5. Subscription
6. Signatura/Signa
7. Renewal
8. Signature, Address and Registration Number of the Prescriber
Date
►Date must be written on the prescription by the prescriber at the same time when it is
written.
►The date on the prescription helps a pharmacist to find out the cases where prescription is
brought for dispensing long time after its issue.
►Prescriptions containing narcotic or other habit-forming drugs must bear the date.
Name, Age, Sex and Address of the Patient
►Name, age, sex and address of the patient must be written on the prescription.
►If it is not written then, the pharmacist himself should ask the patient about these
particulars and put down at the top of the prescription.
►This avoids the possibility of giving the finished product to a person other than the one it
is meant for Patient's full name must be written instead of surname or the family name.
►Age and sex of the patient especially in the case of children helps the pharmacist in
checking the medication and the dose. Therefore, there will be less danger if its being
administered to the wrong member of the family or the hospital ward having similar names.
►The address of the patient is recorded to help for any reference at a later stage, to contact
the patient or to deliver the medication personally.
Superscription
►The superscription is represented by a symbol, Rx, which is always written at the
beginning of the prescription.
►In the days of mythology and superstition, the symbol was considered as prayer to Jupiter,
the God of healing, for quick recovery of the patient but now this symbol is understood as an
abbreviation of the Latin word recipe, meaning "take thou" or "you take".
Inscription
►This is the main part of the prescription.
►It contains the names and quantities of the prescribed ingredients.
►The names of the ingredients are written each on a separate line, followed by the quantity
ordered and the last item written is generally the vehicle or diluent.
►In complex prescriptions containing several ingredients the inscription is divided into three
parts:
i) The base or the active medicament which is intended to produce the therapeutic effect;
ii) The adjuvant which is included either to enhance the action of the medicament or to make
the product more palatable;
iii) The vehicle which is either used to dissolve the solid substances and/or to increase the
volume of the preparation for ease of administration.
Subscription
This part of the prescription contains prescriber's directions to the pharmacist regarding the
dosage form to be prepared and number of doses to be dispensed. Since, nowadays only a
few prescriptions are compounded therefore such directions are less frequent.
Signatura/Signa
►It is usually abbreviated as "Sign" on the prescriptions and consists of the directions to be
given to the patient regarding the administration of the drug.
►It usually indicates the quantity of medicament or number or dosage units to be taken, how
many times in a day or at what time it should be taken and the manner in which it is to be
administered or applied.
Renewal
►The prescriber indicate on every prescription order whether it may be renewed and if so,
how many times.
►It is very important particularly in the prescription containing the narcotic and other habit
forming drugs to prevent its misuse.
Signature, Address and Registration Number of the Prescriber
►All other parts of the prescription may be printed or type-written but the prescriber's name
must be hand-written and should be signed with ink.
►This eliminates the danger of dispensing medicament on a spurious order and it
authenticates the prescription.
►The prescriptions containing narcotic or other habit-forming drugs must bear the address
and registration number of the prescriber.
►This identifies the special license which a prescriber must have to prescribe the narcotic
and other habit-forming drugs.
HANDLING OF PRESCRIPTION

►The following procedure should be adopted by the pharmacist while handling the
prescription for compounding and dispensing:-

1. Receiving
2. Reading and checking
3. Collecting and weighting the materials
4. Compounding, labeling and packing
1. Receiving

►The prescription should be received from the patient by the pharmacist himself.

►While receiving a prescription, a Pharmacist should not change his facial expression which
gives an impression to the patient that he is surprised or confused after seeing the
prescription.

2. Reading and checking

►On receiving a priscription,always check it that it is written in proper format i.e doctors’s
pad or OPD slip of the hospital/nursing home and signed by the prescriber along with date.

►A prescription should always be screened behind the counter. In case of any difficulty in
reading or any doubt regarding the prescription or directions, the pharmacist should consult
other pharmacist or the prescriber.

►But at any circumstances patient should come to know about it before tacking it.

Pharmacist should never guess about the meaning of any illegal or confused word. It may
lead to serious consequences.

►Some times prescription is received on telephone by senior pharmacist. In such case, after
taking down the prescription, it should be verified by repeating it on phone to the prescriber.
It is very important because now a days, the number of drugs with almost the same
pronunciation and spelling are available in the market. For example:

Acidin(R) Apidin(R)

Prednisone Prednisolone

Digoxin Digitoxin

Althrocin Elthrocin

►If there is any omission of any important particulars, such as the dose, the prescriber
should be contacted.
3. Collecting and weighing the material

Before compounding the prescription, all the material required for it, should be collected on
the left hand side of the balance. This gives a check of ingredients which have been weighed.
While compounding, the label of every stock bottle should be read at least three times in
order to avoid any error:

(a)When taken from the left or drawer

(b) When the contents are removed for weighing and measuring.

(c) When the containers are returned back to its proper place.

4. Compounding, labeling and packaging

►Compounding should be carried out in a neat place.

►The equipment required should thoroughly cleaned and dried.

►Only one prescription should be compounding at one time.

►All the ingredients should be compounded according to the directions of the prescriber or
pharmaceutical art.

►The compounded medicaments should be filled in suitable containers depending on its

quantity and use. The filled containers are labeled immediately.

►White plain paper of good quality should be used for labeling the containers.

►The size of the label should be proportional to the size of the container which is written or
typed, giving all the desired information.

►The container is polished so as to remove the finger prints.

►While delivering the prescription to the patients, the pharmacist should explain the mode of
admistration, direction for use and storage.

CARE REQUIRED IN DISPENSING PRESCRIPTION

Following precautions should be taken while dispensing a prescription.

(1)Always keep the prescription before you. Take the prescription with you while taking out
the medicine from the shelf. It will serve as a constant remainder of the name and strength of
the preparation required and helps to avoid mistakes.

(2) Always check the ingredients before weighing which are to be dispensed.

(3)Replace containers of stock preparations or drugs in their proper position after use.
(4)Keep the label in upper position during weighing solid ingredients especially the potent
drugs such as morphine hydrochloride to serve as a constant reminder that the correct drug
being used.

(5)When pouring or measuring the liquid ingredients, keep the label upward in butter paper in
order to prevent surplus liquid running down of the bottle and staining the label.

(6)Care should be taken to keep the dispensing balance clean. The powder should be
transferred from the stock container by using a clean spatula. The scale pan should be cleaned
immediately.

(7)Medicines which are used externally such as lotions, liniments, paints etc.should be
supplied in vertically fluted or ribbed bottles in order to distinguish it by touch. They must be
labeled in red or against a red background.

FOR EXTERNAL USE ONLY

(8)Before handing over the medicine to the patient, again check that the correct preparation,in
the correct strength,has been supplied and correct direction has stated on the label.

SOURCES OF ERRORS IN PRESCRIPTION

Following are the sources of errors which arise in prescription:
1) Abbreviation:
►Abbreviation presents a problem in understanding parts of the prescription order.
►Extreme care should be taken by a pharmacist in interpreting the abbreviation.
2) Name of the Drug:
►There are certain drugs whose name look or sound like those of other drugs.
►Some of the examples of such drugs are as under:
Examples of Drugs often Confused

Digitoxin Digoxin
Prednisone Prednisolone
Indocin Lincocin
Doridon Doxidan
Pabalate Robalate
Ananase Orinase

►Name of the pharmaceutical products have been changed on certain occasion due to the
possible confusion with the name of the other products, e.g., the name of potassium
supplement was changed from Kalyum to Kolyum because of the possible confusion of the
former designation with valium.
3) Strength of the Preparation:

►The strength of the preparation should be stated by the prescriber.

►For example, it will be a wrong decision on the part of a pharmacist to dispense

paracetamol tablet 500 mg when prescription for paracetamol tablet is received with no
specific strength.
4) Dosage Form of the Drug Prescribed:

►Many medicines are available in more than one dosage form.

► For example, liquid, tablet, capsule and suppository. The pharmaceutical form of the
product should be written on the prescription in order to avoid ambiguity.
5) Dose:

►Unusual high or low doses should be discussed with the prescriber.

►For example, a prescription for sustained release formulation to be administered after every
four hours should be thoroughly checked because such dosage forms are usually administered
only two or three times a day.

6) Instructions for the Patient:

The quantity of the drug to be taken, the frequency and timing of administration, and route of
administration should be clearly given in the prescription so as to avoid any confusion.
7) Incompatibilities:

►It is essential to check that there are no pharmaceutical or therapeutic incompatibilities in a

prescribed preparation and that different medicines prescribed for the same patient do not
interact with each other to produce any harm to the patient.
POSOLOGY

►Posology is derived from the Greek word posos meaning how

much and logos meaning science. So posology is the branch of medicine dealing with doses.

►The optimum dose of a drug varies from patient to patient. The following are some of the
factors that influence the dose of a drug.

1. Age:

►Human beings can be categorized into the following age groups:

1. Neonate: From birth up to 30days.

2. Infant: Up to 1 year age

3. Child in between 1 to 4 years

4. Child in between 5 to 12 years.

5. Adult 12-60 Years

6. Geriatric (elderly) patients<60 Years

►In children the enzyme systems in the liver and renal excretion remain less developed.

►So all the dose should be less than that of an adult. In elderly patients the renal functions
decline.

►Metabolism rate in the liver also decreases. Drug absorption from the intestine becomes
slower in elderly patients.

►So in geriatric patients the dose is less and should be judiciously administered.

2. Sex:

►Special care should be taken while administering any drug to women during menstruation,
pregnancy and lactation.

►Strong purgatives should not be given in menstruation and pregnancy.

►Antimalarials, ergot alkaloids should not be taken during pregnancy to avoid deformation
of foetus.

►Antihistaminics and sedatives should not taken during breast feeding because these drugs
are secreted in the milk.
3. Body size:

►It influences the concentration of drug in the body. The average adult dose is calculated
for a person with 70kg body weight (BW). For exceptionally obese (fat) or lean (thin) patient
the dose may be calculated on body weight basis.

►Another method of dose calculation is according to the body surface area (BSA).

►This method is more accurate than the body weight method.

►The body surface area (BSA) of an individual can be obtained from the following formula:

BSA (m2) = BW (kg)0.425 x Height (cm)0.725 x 0.007184

4. Route of administration

►In case of intravenous injection the total drugs reaches systemic circulation immediately
hence the dose is less in i.v. injection than through oral route or any other route.

5. Time of administration

►The drugs are most quickly absorbed in an empty stomach.

►The presence of food in the stomach delays the absorption of drugs. Hence a potent drug is
given before meal. An irritant drug is given after meal so that the drug is diluted with food
and thus produces less irritation.

6. Environmental factors

Stimulant types of drug are taken at day time and sedative types of drugs are taken during
night time. So the dose of a sedative required in day time will be much higher than during
night time. Alcohol is better tolerated in winter than in summer.

7. Psychological state(Emotional factors)

►Psychological state of mind can affect the response of a drug, e.g. a nervous and anxious
patient requires more general anesthetics.

►Placebo is an inert substance that does not contain any drug. Commonly used placebos
are lactose tablets and distilled water injections.

►Some time patients often get some psychological effects from this placebo. Placebos are
more often used in clinical trials of drugs.

8. Pathological states (Presence of disease)

Several diseases may affect the dose of drugs:

►In gastrointestinal disease like achlorhydria (reduced secretion of HCl acid in the stomach)
the absorption of aspirin decreases.

►In liver disease (like liver cirrhosis), metabolism of some drugs (like morphine,
pentobarbitone etc.) decreases.

►In kidney diseases, excretion of drugs (like aminoglycosides, digoxin, phenobarbitone) are
reduced, so less dose of the drugs should be administered.

9. Accumulation

►Any drug will accumulate in the body if the rate of absorption is more than the rate of
elimination.

►Slowly eliminated drugs are often accumulated in the body and often causes toxicity e.g.
prolonged use of chloroquin causes damage to retina.

10. Drug interactions

Simultaneous administration of two drugs may result in same as synergetic or increased or

decrease the antagonistic effects.

Drug administration with dose Pharmacological effect

Drug A Effect A
Drug B Effect B
Drug A + Drug B Effect AB

Relationship Name of the effect Examples

Effect AB = Effect A + Effect B Additive effect Aspirin + Paracetamol
Effect AB > Effect A + Effect B Synergistic (or Sulfamethaxazole +
potentiation) Trimethoprim
Effect AB < Effect A + Effect B Antagonism Histamine + Adrenaline
11. Idiosyncrasy

This exceptional response to a drug in few individual patients. For example, in some patients,
aspirin may cause asthma, penicillin causes irritating rashes on the skin etc.

12. Genetic diseases

Some patients may have genetic defects. They lack some enzymes. In those cases some drugs
are contraindicated.

e.g. Patients lacking Glucose-6-phosphate dehydrogenase enzyme should not be

given primaquin (an antimalarial drug) because it will cause hemolysis.

13. Tolerance

Some time higher dose of a drug is required to produce a given response (previously less dose
was required).
Natural Tolerance: Some races are inherently less sensitive to some drugs, e.g. rabbits and
black race (Africans) are more tolerant to atropine.

Acquired Tolerance: By repeated use of a drug in an individual for a long time require
larger dose to produce the same effect that was obtained with normal dose previously.

Cross tolerance: It is the development of tolerance to pharmacologically related drugs e.g.

alcoholics are relatively more tolerant to sedative drugs.

Tachyphylaxis: (Tachy =fast, phylaxis =protection) is rapid development of tolerance. When

a dose of a drug is repeated in quick succession an reduction in response occurs – this is
called tachyphylaxis. This is usually seen in ephedrine, nicotine.

Drug resistance: It refers to tolerance of microorganisms to inhibitory action of

antimicrobials e.g. Staphylococci to penicillin.

CALCULATIONS OF DOSES FOR CHILDREN

A number of methods have been used to relate doses for children to their ages.

1. Dose proportionate to age

(i)Young’s formula: This formula is used for children having age below 12 years.

Dose of the child=Age in years/Age in years+12 X Adult dose

The formula is used for calculating the doses for children under 12 years of age.

(ii)Dilling’s formula: This formula is used for children having age from 4 to 20 years. This
formula is better because it is easier to calculate the dose.

Dose for child=Age in years/20 X Adult dose.

2. Doses proportionate to body weight

Clark’s formula is used for used to calculate the dose for the child according to body weight.

Clark’s formula:

Dose of the child=Child’s weight in Kg/70 X Adult dose.

3. Doses proportionate to body surface area (BSA)

The calculation of child dose according to surface area is more satisfactory and appropriate
rather than the method based on age. The method is more complicated than the method based
on age. The method is based on the following formula:

Percentage of adult dose=Surface area of child/Surface area of adult X Adult dose

The body surface area is calculated from the height and weight of the child.
UNIT 2: PHARMACEUTICAL CALCULATIONS: POWDERS: LIQUID DOSAGE
FORMS:

ISOTONIC SOLUTIONS

Solutions having the same osmotic pressure are called iso-osmotic. It is not necessary
that solutions which are iso-osmotic will also be isotonic. If a red blood cell is in contact with
a solution that has the same osmotic pressure as that of blood plasma, the cell wall will
neither swell nor shrink i.e. it will retain its tone and therefore the solution is said to be
“isotonic”.

To determine whether or not a solution is isotonic with erythrocytes, it is necessary to

determine the concentration of the solute at which the cells retain their normal size and shape.
The parenteral solutions and ophthalmic solutions need adjustment to iso-osmoticity and
isotonicity.

The solutions which are not having the same osmotic pressure are called ‘paratonic’.
While comparing a solution with the one of known osmotic pressure, those which exert a
greater pressure are called ‘hypertonic’ and those with a lower pressure are called
‘hypotonic’. Blood plasma contains 0.88% of inorganic salts, mainly sodium chloride, which
make the main contribution to osmotic pressure.

A solution containing 0.9% of sodium chloride is, therefore, practically isotonic with
blood plasma and is regarded as standard. A solution containing more than 0.9%sodium
chloride is called ‘hypertonic’ and one containing less than that is called ‘hypotonic’.

General principles for adjustment to Isotonicity:

1. Solution for i/v injection: approximate isotonicity is always desirable.

2. Solution for s/c injuction: isotonicity is needed butt is not essential, since they are injected
into fatty tissues and not in blood stream.

3. Solution for i/m injection: the aqueous solutions should be slightly hypertonic to promote
rapid absorption.

4. Solution of intra-cutaneous injection: The parenteral preparations which are meant for
diagnostic purpose should be isotonic in order to avoid the false reaction.

5. solutions for intrathecal injection: These must be isotonic, because the volume of C.S.F is
only 60 – 80ml.

6. Solutions used for nasal drops: Isotonicity is needed, since paratonic solution may cause
irritation.

7. Solutions used as eye drops and eye lotion: Eye lotion should be isotonic with lachrymal
secretion, since a large volume is brought in contact with the eye. Eye drops may not be
isotonic , because only a small volume is used which quickly get diluted by the lachrymal
Secretion.

Calculations for adjustment to isotonicity:

1. Based on freesing point method:

Percentage w/v of adjusting substance needed = 0.52-a / b

Where:

a= freezing point of the unadjusted solution

b = freezing point of a 1% w/v solution of the adjusting substance.

2. Based molecular concentration:

Percentage w/v of adjusting = 0.03M/N

Where:

M= gram molecular weight of the substance

N= number of ions which the substance is ionized.

Example 1

Find out the proportion of procaine hydrochloride which will yield a solution iso-osmotic
with blood plasma.

(Given: the freezing point of a 1% w/v solution of procaine hydrochloride is -0.1220 C)

Calculation by applying the formula:

Percentage w/v of sodium chloride required=0.52-0.00/0.122

= 4.26% w/v.

Example 2

Find out the concentration of sodium chloride required to make a 1% solution of boric
acid, iso-osmotic with blood plasma.

(Given: the freezing point of a 1% w/v solution of boric acid is -0.2880 C). The
freezing point of a 1% w/v solution of sodium chloride is -0.5760 C).

Calculation by applying the formula:

Percentage w/v of sodium chloride required=0.52-0.288/0.576

= 0.402% w/v
Example 3

Find out the concentration of sodium chloride required to make a 1.5% solution of
cocaine hydrochloride iso-osmotic with blood plasma.

(Given: the freezing point of a 1% w/v solution of cocaine hydrochloride is -0.090 C).
The freezing point of a 1% w/v solution of sodium chloride is -0.5760 C).

Calculation by applying the formula:

Percentage w/v of sodium chloride required=0.52-(0.09X1.5) / 0.576

= 0.668% w/v

Example 4

Find out the concentration of sodium chloride required to make 50ml of isotonic solution
containing 0.5% ephedrine hydrochloride and 0.5%chlorobutol.

(Given: the freezing point of a 1% w/v solution of ephedrine hydrochloride is -0.1650

C). The freezing point of a 1% w/v solution of chlorobutol is -0.1380 C).

Calculation by applying the formula:

Percentage w/v of sodium chloride required= 0.52-0.1515 / 0.576

= 0.644% w/v.

Example 5

Find out the proportion of dextrose, which will yield a solution iso-osmotic with
blood plasma.

Calculation by applying the formula:

Molecular weight of dextrose = 180

Dextrose is non-ionizing substance.

Hence the formula used is W= 0.03M

W = 0.03X180

Or

W = 5.4g/100ml.
Example 6

Find out the concentration of sodium chloride required ot produce a solution iso-
osmotic with blood plasma.

Calculation by applying the formula:

Molecular weight of sodium chloride = 58.5

Sodium chloride is ionizing substance and it gets 2 ions..

Hence the formula used is W = 0.03M

W = 0.03X58.5 /2

Or

W = 0.88g/100ml.

Alcohol dilutions:

The dilute alcohols are made from 95% alcohol, which contains 95 parts by volume of
ethyl alcohol and 5 parts by volume of water.

When alcohol gets mixed with water, the following changes take place:-

1. There is rise in temperature.

2. There is contraction in volume.

3. There is turbid appearance in the solution.

4. Solubility of air is more in alcohol than in water.

5. When alcohol is diluted with water, minute bubbles of air are evolved from the
alcohol and make the turbid appearance.

The following examples illustrate the method of calculating alcohol dilutions.

Example 1

Calculate the amount of 95% alcohol require to prepare 400ml of 45%alcohol

Calculation:

Percentage of alcohol required = 45

Percentage of alcohol used = 95

 By applying formula:

Volume required X percentage required

Volume of stronger alcohol to be used =

Percentage used

= 400 X 45 / 95

= 3600 / 19

= 189.47 ml

= 190 ml (approx).

Example 2

Calculate the amount of 95% alcohol require to prepare 600ml of 60%alcohol

Calculation:

Volume required = 600ml

Percentage of alcohol required = 60

Percentage of alcohol used = 95

By applying formula:

Volume required X percentage required

Volume of stronger alcohol to be used =

Percentage used

= 600 X 60 / 95

= 3600 / 95

= 378.9 ml

= 379ml (approx).
ALLEGATION METHOD

The Allegation method is used when the calculation involves mixing of two similar
preparations off different strength, to produce a preparation of intermediate strength. The
method is recommended for checking the calculations.

For calculation purpose, the figures are written as given below:-

Stronger Weaker
percentage percentage

Required
percentage

Required Stronger
percentage percentage

Weaker Required
percentage percentage
The following example illustrates the use of this method:

Example 1

Calculate the amount of 95% alcohol require to prepare 600ml of 70%alcohol

Calculation:

Volume required = 600ml

Percentage of alcohol required = 70

Percentage of alcohol used = 95

By using allegation method:

Alcohol water

95 0

70

70-0 =70 95-70=25

 70 parts of 95% alcohol and 25 parts of water will produce the required parentage
alcohol.

Quantity of 95% Percentage of alcohol required = 600 X 70 / 95

= 442.10ml

Quantity of water required = 600 X 25 / 95

= 157.90ml

Example 2

Calculate the strength of alcohol if 250ml of 20% v/v alcohol, 450ml of v/v alcohol
and 500ml of 30% v/v of alcohol is mixed together.

Calculation:

250ml of 20% v/v alcohol contains alcohol = 50ml

450ml of 40% v/v alcohol contains alcohol = 180ml

500ml of 30% v/v alcohol contains alcohol = 150ml

1200ml of mixture of alcohol contains alcohol = 380 ml

Suppose v ml of alcohol is present in 100ml of mixture apply the ratio – proportion

rules:-

1200: 380: 100: V

V = 380 X 100 / 1200 = 32ml

Therefore, 32% v/v is the strength of alcohol in a mixture.

Example 3

Calculate the proportion of 15%, 8% and 3% alcohol required to make 6% of alcohol.

Using the allegation method:

15 3 parts of 15% alcohol

8 6 2 parts of 8% alcohol

3 9 parts of 3% alcohol
Therefore, when 3 parts of 15% alcohol, 2 parts of 8% alcohol and 9 parts of 3 % alcohol are
mixed together, the resulting solution will produce 6% alcohol.

Example 4

Calculate the proportion of 20%, 15% and 5% alcohol should be mixed to get to
produce 150ml of 6% alcohol.

Using the allegation method:

20 1parts of 20% alcohol

15 6 9 parts of 15% alcohol

5 14 parts of 5% alcohol

Therefore, when 1 parts of 20% alcohol,9 parts of 15% alcohol and 14 parts of 5 %
alcohol are mixed together, the resulting solution will produce 8% alcohol.

1. Volume of 20% alcohol required

24 parts: 150ml: 1 parts: V

V = 150 X 1 / 24 = 6.25ml

2. Volume of 15% alcohol required

24parts : 150ml : 9 pats : V

V = 150 X 9 / 24 = 56.25ml

3. Volume of 5% alcohol required

24parts : 150ml : 14 pats : V

V = 150 X 14 / 24 = 87.5 ml

Example 5

Calculate the proportion of 70%, 60%, 40% and 30% alcohol should be mixed to get to 50%
alcohol.
Using the allegation method:

70 20 parts of 70% alcohol

60 10 parts of 60% alcohol

50

40 10 parts of 40% alcohol

30 20 parts of 30%
alcohol

Therefore, when 20 parts of 70% alcohol, 10 parts of 60% alcohol, 10 parts of 40%
alcohol and 20 parts of 30% alcohol are mixed together, the resulting solution will produce
50% alcohol.

Check:

= (20 x 70)+ (10 x 60)+ (10 x 40)+ (20 x 30)

= 1400 + 600 + 400 + 600

= 3000.

Example 6

Calculate the proportion of 90%, 60%, 30% and water are required to produce 500ml
of 50% alcohol.

Using the allegation method:

90 50 parts of 90% alcohol

60 20 parts of 60% alcohol

50

30 10 parts of 30% alcohol

0 40 parts of of water
 Therefore, when 50 parts of 90% alcohol, 20 parts of 60% alcohol, 10 parts of 30%
alcohol and 40 parts of water are mixed together, the resulting solution will produce 50%
alcohol.

1. Volume of 90% alcohol required

120 parts : 500ml : 50 parts : V

V = 500 X 50 / 120

= 2500/12

= 208.33ml

2. Volume of 60% alcohol required

120 parts: 500ml : 20 pats : V

V = 500 X 20 / 120

= 1000/12

= 83.33ml

3. Volume of 30% alcohol required

120 parts: 500ml : 10 pats : V

V = 500 X 10 / 120

= 500/12

= 41.67ml

4. Volume of water required

V = 500 – 208.33 – 83.33 – 41.67ml

V = 166.67ml.

PROOF SPIRIT

For excise purpose, the strength of alcoholic preparations is indicated by degree,

“over proof” or “under proof”. Proof spirit is that mixture of alcohol and water which at 51 oF
weights 12/13th of an equal volume of water. In India, 57.1 volume of ethyl alcohol is
considered equal to 100 volumes of proof spirit. This means that any alcoholic solution,
which contains 57.1% v/v alcohol, is a proof spirit which is said to be 100 proof. So any
strength above proof strength is expressed as over proof (OP) and any strength below proof
strength is expressed as under proof (UP).
 In India, the excise duty is calculated in terms of rupees per litre of proof alcohol. So
any percentage volume in volume of alcohol can be converted into proof strength and vice
versa by using the following method:

1. Multiply the percentage strength of alcohol by 1.753 and deduct 100 from the
product.

2. If the result is positive, it is known as over proof.

3. If the result is negative, it is known as under proof.

Example 1

Find the strength of 95% v/v alcohol in terms of proof spirit.

By applying the formula:

Percentage strength of alcohol X1.753 – 100

= 95 x 1.753 – 100

= 166.53 – 100

= +66.53O

(or)

= 66.53O OP.

Example 2

Calculate the real strength of 30O OP. and 40O UP.

30 over proof means 100+ 30 =130

Alcohol strength =130 / 1.753 = 74.15% v/v

40 under proof means 100 - 40 = 60

Alcohol strength =60 / 1.753 = 34.23% v/v

Check:

If strength is 74.15% v/v

= 74.15 x 1.753 – 100 = 129.9 – 100

= +29.9O or 30O OP.

If strength is 34.23% v/v

= 34.23 x 1.753 – 100

 = 60 – 100

= -40O.

Or

= 40O UP.

Example 3

How many proof gallons are contained in 5 gallon of 70% v/v alcohol.

Applying formula:

Value in proof = % strength of alcohol X1.753 – 100

= 70 X 1.753 – 100

= 122.71 – 100

= +22.71O or

= 22.71OP.

That means

100 gallons of 70% v/v alcohol = 122.71 units of spirit

1 gallon of 70% v/v alcohol = 122.71 / 100

5 gallons of 70% v/v alcohol = 122.71 X 5 / 100.

= 6.1355 gallons of proof spirit.

Therefore, 5 gallons of 70% v/v alcohol are equivalent to 6.1355 gallons of proof spirit.

Milliequivalents:

The quantity of electrolytes administered to patients is usually expressed by the term

milliequivalents (mEq). A mEq is 1 / 1000th of an equivalent (Eq). an Eq is the weight of
substance which combines with or replaces one gram – atomic weight of hydrogen. An Eq or
Eq. wt.are interchangeable terms. Equivalent weight (Eq.wt) is the weight in grams of an
atom or radical divided by the valence of the atom or radical.

Example 1

Calculate the mEq wt of calcium (ca++).

Given: gram – atomic wt of calcium =40.08

 Gram – atomic weight

mEq =

Valence

= 40.08 / 2

= 20.04 g.

mEq = Eq / 1000

= 20.04 / 1000

= 0.02004g

= 20.04mg.

Example 2

Calculate the mEq of sodium (Na+), and Cl- in a solution that contains 409.5mg of
Nacl / 100ml.

Eq wt of sodium chloride = 58.5g

mEq wt of sodium chloride = 58.5 / 1000

= 0.0585g

= 58.5 mg

409.5mg

mEq = = 7 mEq

58.5mg / mEq

Of NaCl which dissociates 7 mEqof Na+ and 7 mEq of Cl-.

Example 3

A vial of sodium chloride injection contains 3 mEq / ml. calculate the percentage
strength of the solution.

Eq.Wt of sodium chloride = 58.5g

3 mEq / ml =3003 mEq / 100ml

mEq wt of sodium chloride = 58.5mg

58.5 mg /mEq X 300 3 mEq / 100ml =17550 mg / 100ml

(or)
 17.6g/ 100ml

(or)

17.6% solution.

Example 4

Express 0.9%sodium chloride solution in terms of milliequivalent per litre.

Eq.Wt of sodium chloride = 58.5g

Concentration of sodium chloride = 0.9% w/v

mEq / litre = 0.9 X 10000 / 58.5 =154 mEq / litre.

Hence, 0.9% w/v solution of sodium chloride can be expressed in terms of 154
mEq/litre.
FUNDAMENTAL OPERATIONS IN COMPOUNDING

Compounding and dispensing is concerned with the preparation of medicine from basic
ingredients on a small scale. The accurate and elegant compounding of medicines requires
expertise in several fundamental operations which are as under:

1. Weighing

2. Measurement of liquids

3. Dissolution

4. Filtrations

5. Mixing

6. Size reduction

7. Size separation

1. WEIGHING

Weighing is one of the most important steps which are needed in almost all types of
pharmaceutical applications. The success of all these operations in the pharmacy depends on
a proper weighing which is possible only if there is thorough knowledge of balance, its
principle, its care and proper use.

During compounding and dispensing of medicines, weighing is done on dispensing balance.

A dispensing balance consist of simple light but rigid,equel armed horizontal beam with
central and terminal knife edges of steel which work in agate or steel bearing. two pans are
suspended from the terminal knife edges. One of pans which is made of glass is used for
placing the material for weighing the other pan made of metal and used for keeping the
weight on it. when the load is placed in the pans the beam turns about the central fulcrum and
deflection from the horizontal is indicated by the movement of a pointer fixed below the
centre of the beam.
 Dispensing balance.

The fallowing techniques should be followed while weighing the material:

1. Place the balance in a convenient position for use. the area should be well-lit and free from
dust.

2. Adjust the level of the balance.

3. Clean the balance and pans with a dry duster before use.

4. Place a clean white sheet of paper under each pan and replace it frequently to protect the
balance from corrosion.

5. Place the required weights on the left hand pan with the help of forceps so that sweat and
grease from the hands may not make weights in inaccurate.

6. Close the drawer on the balance in order to prevent spillage of the powder on the weights
lying in the drawer.

7. Remove the bottle of medicament from the shelf and check its label for the correct
ingredient mentioned in the prescription.

8. Hold the bottle in the left hand with the label in upper position so that it is visible during
weighing.

9. Add or remove the medicament to the right hand pan with the help of spatula until the
pointer returns to o the null point. In pharmacy, the right hand pan is used for the material
being weighed.

10. When the weighing is completed put the balance beam again in a fixed position.

11. Transfer the weighed material in a container or on a piece of paper as per requirement.

12. Return the weights to the drawer with forceps and carefully clean the balance pan and
spatula.
13. Close the bottles and again check its label. Return the bottles to the shelf at a time for
weighing and the same should be replaced immediately after weighing the material from it.
Then the next bottle should be removed and weigh the material. this will help to avoid the
mistake if a number of bottles are kept on the working table together.

Possible errors in weighing:

During weighing there can be chances of error which may occur due to the following reasons:

1. The balance is not properly leveled.

2. The rest point of the balance is not correct.
3. The two pans of the balance are of unequal weights.
4. The surfaces of the pans are rough.
5. The material is weighed directly on the pan.
6. The material is weighed even though the pans are still oscillating.
7. Weights are handled with hand and not with forceps.

Sources of error

Some of the sources of error in weighing are:

• Buoyancy, Objects in air develops buoyancy(Floating,Light) force that is directly

proportional to the volume of air displaced. The difference in density of air due to
barometric pressure and temperature creates errors.
• Error in mass of reference weight
• Air gusts(Sudden violent rush of wind), even small ones, which push the scale up or
down
• Magnetic fields acting on ferrous components
• Chemical reactivity between air and the substance being weighed (or the balance
itself, in the form of corrosion)
• Condensation of atmospheric water on cold items
• Evaporation of water from wet items
• Convection of air from hot or cold items

Proper care and usage of dispensing balance:

It is the general tendency among the pharmacists that they do not take care of the
dispensing balance during its use or protecting it when it is not in use. Dispensing balance is
the part and parcel of a pharmacist while compounding and dispensing of medicines at the
counter. So it becomes necessary for a pharmacist to take proper care of it. The following
points should always be kept in mind for proper care and usage of dispensing balance:

1. It should be kept in a place which is free from dust, humidity and corrosive vapors of
certain chemicals.
2. It should be kept on a smooth plane slab or on a stable table.
3. Clean the pans of the dispensing balance with a clean duster before and after its use.
4. Never keep the weight or the medicament on the pan when the beam of the balance is
free to oscillate.
 5. Greasy and waxy substances should be weighed on a counter balance sheet of wax
paper to prevent the spoilage of the pan of the balance.
6. Always use spatula to transfer any material from the bulk packing to the pan.
7. The drawer of the balance should be closed while weighing the material.
8. The weights should be transferred with forceps.
9. After using the balance, it should be cleaned immediately with soft cloth or brush
taking care that the delicate balancing mechanism of the balance is not disturbed.
10. When the balance is not in in use, it must be cleaned and covered with balance cover.

Electronic Balance

Microbalance

A microbalance is an instrument capable of making precise measurements of weight of

objects of relatively small mass of the order of a million parts of a gram.

Analytical balance

Mettler digital analytical balance with 0.1 mg readability.

An analytical balance is a class of balance designed to measure small mass in the sub-
milligram range. The measuring pan of an analytical balance (0.1 mg or better) is inside a
transparent enclosure with doors so that dust does not collect and so any air currents in the
room do not affect the balance's operation. This enclosure is often called a draft shield. The
use of a mechanically vented balance safety enclosure, which has uniquely designed acrylic
airfoils, allows a smooth turbulence-free airflow that prevents balance fluctuation and the
measure of mass down to 1 μg without fluctuations or loss of product. The sample must be at
room temperature to prevent natural convection from forming air currents inside the
enclosure from causing an error in reading. Single pan mechanical substitution balance
maintains consistent response throughout the useful capacity is achieved by maintaining a
constant load on the balance beam.

Electronic analytical scales measure the force needed to counter the mass being measured
rather than using actual masses. As such they must have calibration adjustments made to
compensate for gravitational differences. They use an electromagnet to generate a force to
counter the sample being measured and outputs the result by measuring the force needed to
achieve balance. Such measurement device is called electromagnetic force restoration sensor.

Taring the weighing vessels

When adjustment of a product to weight is required, knowledge of the weight of the vessel
containing the preparation is needed. It is usually inconvenient to obtain the weight are
required, one containing a quantity of small lead shot. The vessel to be tarred is placed on one
balance pan and the empty container on the other. The shot is poured in to the container until
balance is obtained. The container is then retained and used as a tare for the vessel when
required.

The weighing of the empty vessel may be easily recorded with an electronic balance. The
other alternative is to reset the balance to zero and the tare automatically retained provided
that adjustment should not be disturbed before the preparation is completed.

Weighing by difference

It is difficult to weigh viscous substances because it is not possible to transfer them

completely from the weighing vessel. So the best method to weigh a slight excess of the
substance which remains in the weighing vessel after the correct amount has been transferred.
The following procedure may be used to weigh by difference.

1. Place a weighing vessel on the right hand pan of the dispensing balance and
counter balance with a similar weighing vessel.
2. Put weigh for the required amount of substance on the left hand pan.
3. Add the substance to the right hand vessel until balance is obtained and then add
an excess.
4. Place more lead shot on the left hand pan to make up the balance.
5. Remove the weigh from the left hand pan and carefully transfer the substance
from the fight hand pan until the balance is again restored, when the appropriate
weigh of the substance will be removed. Discard the excess.
Minimum weighable amounts

The recommended minimum weighable quantity of any substance to be used in compounding

is 50mg, provided that a ‘class A’ sensitive balance is used for weighing. In case of ‘class B’
balance the minimum weighable quantity is 100mg. when dispensing balance is used for
weighing, a minimum weighable quantity should not be less than 2 gm or 100 mg.

Now a day the majority of the practitioners avoid writing prescription of powder in very
small doses, but still some practitioners write prescription of powder very small doses. In that
case, following procedure should be followed for dispensing quantities below the minimum
weighable amount:

1. By using digital single pan balance or an analytical balance for weighing a very small
quantities of potent drug. There are usually a very few prescriptions of this type and it
is not economical to procure a costly balance to dispense such prescriptions.
 2. By using prefabricated dosage from, such as tablet triturates, dispensing tablets or
hypodermic tablets of the same drug for the convenience of patient and pharmacist.
3. By taking the minimum weighable quantity of potent drug and triturate it with a solid
diluents such as lactose. Dispense the triturate in powder containing the required dose
of the drug. Lactose is generally preferred as diluents because it is white, inert, and
sweet in taste, economical, easily available and compatible with large number of
drugs.
The following factors must be considered while preparing trituration and dilutions:

a. The quantity of the medicament to be diluted should not be less than the minimum
weighable quantity.
b. The final dilution prepared after trituration with diluents must contain the required
amount of the drug in minimum weighable amounts.
The dilution of minimum weighable amount of the drug is done with diluents in a
geometrical proportion known as geometrical dilution.

2. MEASUREMENT OF LIQUIDS

Some chemistry glassware, called volumetric glassware, is inscribed with markings to make
measuring the volume of liquids easier. The pieces of volumetric glassware found in the
chemistry laboratory are beakers, Erlenmeyer flasks, graduated cylinders, pipettes, burettes
and volumetric flasks.

Beaker Erlenmeyer flask

Graduated cylinder Pipette

 Burettevolumetric flask

To Deliver and To Contain

Volumetric glassware can be divided into two categories: those designed to contain a
specified amount of liquid and those designed to deliver a specified amount of liquid.
Glassware designed to contain, like graduated cylinders and volumetric flasks, are usually
marked with a TC.

When liquid is poured from a piece of glassware a small amount remains behind, clinging to
the sides of the vessel. A 100 ml volumetric flask is designed to hold exactly 100 ml, but if
the liquid is poured out it will actually deliver a little less than 100 ml. Glassware designed to
deliver, like pipettes and burettes, are marked with a TD.
These pieces of glassware account for the small amount of liquid that remains behind. A 100
ml pipette contains a little more than 100 ml of liquid, but when the liquid is drained from a
pipette, exactly 100 ml is delivered.

The Meniscus
When water is placed in a glass or plastic container the surface takes on a curved shape. This
curve is known as a meniscus. Volumetric glassware is calibrated such that reading the
bottom of the meniscus, when it is viewed at eye level, will give accurate results. Viewing the
meniscus at any other angle will give inaccurate results.

Accuracy
The accuracy of the markings on volumetric glassware varies greatly. The markings on
beakers and flasks are usually about plus or minus 5% of the volume of the container. As
such, they should be used only when a rough estimate of volume is required. The tolerance on
graduated cylinders is about 1%. Volumetric flasks, burettes and pipettes are the most
accurate with tolerances of less than 0.2%. To achieve these accuracies the person using the
device needs to use the proper technique and the measurements need to made at the
temperature for which the glassware was calibrated (usually 20 degrees C).
Proper Technique
Read about proper pipette technique. Read about proper burette technique.

Using a Volumetric Pipette

Pipettes come in a variety of sizes which usually range from 1 ml up to 100 ml.

1. Rinse the pipette two or three times with the liquid you wish to transfer. Do this by
drawing a small amount of liquid into the pipette, turning the pipette horizontally and
rotating it so that the liquid contacts the entire inside surface of the pipette. Let the liquid
drain into a waste container.

2. If you are right handed place the pipette in your right hand and the pipette bulb in your
left (left handed people do the opposite).
 3. Squeeze the bulb and place it over the end of the pipette. The pipette should not be forced
into the hole in the pipette bulb. A satisfactory seal can be made if the two are pushed up
against each other.

4. Place the end of the pipette well below the surface of the liquid to be transferred and
gentlyrelease the bulb. Liquid should be drawn up into the pipette. Allow the liquid to
rise above the inscribed line on the pipette.

5. Quickly remove the bulb from the pipette (this is why you don't push the pipette into the
bulb) and cover the opening with your right index finger.
6. Remove the pipette from the liquid and wipe any droplets off the side of the pipette.

7. Gently release the seal with your finger and allow the liquid to drain until the liquid level
reaches the inscribed mark. This is most easily accomplished by releasing the pressure of
your finger and rotating the pipette between your fingers.

8. Touch the pipette to the surface of the liquid or side of the container to remove any partial
drops still clinging to the pipette.

9. Place the tip of the pipette into the receiving vessel and remove your finger to allow the
liquid to drain. Touch the pipette once to the side of the vessel. There will be a small
amount of liquid in the tip. Most pipettes are calibrated to account for this liquid.
SOLID DOSAGE FORM
Solid dosage formulations are the most important dosage forms for pharmaceuticals, e.g.
tablets, capsules, granules, powders, sachets, reconstitutable powders, dry powder inhalers
and chewable. With wide range of high quality excipients and active pharmaceutical
ingredients for all applications, including solutions or bioavailability enhancement and
provide everything need for final product.

Advantages of Solid Dosage Form

•These are more stable dosage forms.

•Less product spoilage during transportation.

•Less space is needed to store.

Disadvantages of Solid Dosage Forms

•Some patients like children cannot swallow

•Some of the drugs resist into dense compacts, owing to their amorphous nature or flocculent,
low-density character.

Classification

Solid dosage are mainly classified into two types as follows

1.Bulk Dosage form

2.Unit Dosage Form

POWDERS

Pharmaceutical Powders are solid dosage form and is a mixture of finely divided drugs or
chemicals in a dry form meant for internal or external use.

Advantages

1. Flexibility of compounding.

2. Good chemical stability

3. Rapid dispersion of ingredients (because of small particle size)

4. Powders are one of the oldest dosage forms and are used both externally and internally.

5. The chances of incompatibility are less as compared to liquid dosage form.

6. Powders are easier to carry than the liquid dosage forms.

7. Large quantity of powdered drugs can be easily administered to the patient orally by
dissolving or mixing the powder in a suitable liquid.
Disadvantages

1-Time-consuming preparation

2- Inaccuracy of dose (size of measuring spoon, density of powder, humidity, degree of

settling, fluffiness.

3-Unsuitability for many unpleasant tasting, hygroscopic and deliquescent drugs

4. Quantity less than 100 mg or so, cannot be weighed conveniently on dispensing balance.

Classification: Powder are mainly classified into three types as follows

1. Bulk powder for internal use

2. Bulk powder for external use, e .g. dusting powders and Insufflations.

3.Divided powders (i.e. single dose) e.g. simple and compound

powder for internal use

1. Bulk powder for internal use

Preparation:

Whenever several powder ingredients are present the powders are mixed in ascending order
of bulk in a mortar. At each addition, a quantity that is approximately equal the bulk already
existed in the mortar is added.

Example:

Compound Calcium Carbonate

Powder

Sodium bicarbonate
37.5g

Calcium carbonate
37.5g

Heavy Magnesium carbonate

12.5g

Light Kaolin 12.5g

Container: Kept in a well-closed, air tight container.

Mode of use: Prescribed amount is dissolved in required amount of water and taken orally.
2. Bulk powder for external use

Classification:

A. Dusting powder - (a) Medical powder,(b) Surgical dusting powder

B. Insufflations

C. Dentifrices (tooth powder)

A (a) Medical dusting powder

These are used for superficial skin conditions. They are not sterile. They are not applied on
open wounds or broken skin.

Ingredients: Purified Talc, Light kaolin, Starch etc. They contain powdered drugs. Talc,
kaolin are mineral ingredients. They may be contaminated with spores of Clostridium tetani
and Clostridium welchii. So talc or kaolin must be sterilized by heating at 1600C for one
hour.

Preparation:

After mixing the powders in a mortar it passed through a mesh no. 120 to remove gritty
particles. Then it is packed in a suitable container.

Container: Dusting powder is packed inside a sifter-top container.

(It is a container with holes in the cap. Whenever the container is shaken the powders are
spread on the skin.)

Example:

Starch salicylic acid dusting powder

Starch,inpowder 75g

Zinc oxide 20g

Salicylic acid, in powder5g

A (b) Surgical dusting powder

These are used in body cavities and major wounds, on burns and on the umbilical cords of
newborns, hence they must be sterile.

They often contain an antibacterial agent and the diluents may be sterilized maize starch.

Example: Chlorhexidine B.P.C., Hexachlorophene B.P.C.

 B. Insufflations

Finely divided powders intended for application to body cavities such as tooth socket, ears,
nose, vagina and throat are known as insufflations. N apparatus is used to deliver a stream of
finely divided powder particles to the site of application is called an insufflator.

They are used to produce either –

(a) A local effect as in the treatment of ear, nose and throat infections with antibiotics or

(b) A systemic effect from a drug that is destroyed in the intestine.

The diluents used in nasal mucosa are lactose and used on open wound is sterilizable maize
starch.

Container: Well-closed container supplied with an insufflators instrument.

The required dose of powder is taken in the container of the insufflators and with the bulb a
pressure is given to force the powder through the nozzle.

Storage: With moisture the nozzle of the insufflators may get choked hence. The powder
must be kept in a dry place and in a well closed container.

C. Dentifrices (tooth powders)

Powders used to clean the teeth are called dentifrices. It is applied with a tooth brush. They
contain

(i) a suitable detergent – hard soap powder

(ii) A suitable abrasive agent – calcium sulfate, magnesium carbonate, dibasic
calcium phosphate

(iii)Sweetening agent – sodium saccharin

(iv) Flavoring agent – peppermint oil, clove oil etc.

Packaging: Sifter top metallic or plastic container.

3. Divided powders (i.e. single dose)

In this form of powder each dose is separately enclosed in a piece of paper.

Classification:

(a) Simple powder: Contains only one ingredient.

(b) Compound powder: Contains more than one ingredient.

The total amount in each dose should not be less than 120mg so that the powder is large
enough to be handled conveniently.
 Packing:

(1) For wrapping divided powders, white glazed paper (demy paper) is generally used.

(2) The powder wrappers are stacked in a paper box and dispensed.

(3) Some time double wrapping is required, especially if the powder is hygroscopic. In this
case waxed paper is used as inner wrapper, then the semi wrapper as the outer wrapper.

General method of preparation of powders

1. Spatulation: If the solids form eutectic mixture, they form liquid on trituration. In this case
they should be mixed lightly with a spatula.

2. Trituration: The solids are taken in a mortar and triturated with a pestle. This method reduced
the particles and at the same time mixes the powders.

3. Geometric dilution: This method is used when very small amount of potent drug is to be
mixed with large amount of diluents. This method can be explained with an example:

For example, say 100mg of a potent drug (A) is to be mixed with 900mg of diluents (B), and
then the geometric dilution method is as follows:

(i) 100mg A + 100mg B → 200mg mixture

(ii) 200mg mixture + 200mg B → 400mg mixture

(iii 400mg mixture + 400mg B → 800mg mixture

(iv) 800mg mixture + rest of B → 1000mg mixture

4. Sifting: the powders are mixed by passing through sifters. This process results in a light fluffy
product and is generally not acceptable for incorporation of potent drugs into a diluents base.

5. Tumbling: Tumbling is the process of mixing powders in a large container rotated by an electric
motor. These blenders are widely used in industry as a large volume powder mixers.

EFFERVESCENT POWDERS

Definition: Mixture of organic acid and alkali effervesces when subjected to water due to reaction

between the acid and the base with evolution of co2

Examples: Citric or tartaric acids with sodium carbonate or bicarbonate.

Uses: The liberated carbon dioxide has the following advantages:

It masks the bitter taste.

It promotes gastric secretions.

It acts as a carminative.

Psychological impression at the patient.

Formulation:

1. Bulk powders or divided powders

- Packed in separate packages of contrasting colors.

- The contents are mixed in a quantity of water at the time of dosing.

- The liquid is consumed just after the reaction begin to subside.

2- Effervescent Granules

Definition: Sweetened effervescent powders formulated as granules.

Granulation:

1.Wet method: By the addition of a binding liquid (Alcohol is frequently used).

2.Dry method: Heating effloresced powder to liberate the water of crystallization which then acts as
the binding agent.

2- Effervescent Granules: Wet Granulation

Procedure

1.The powders are mixed without pressure in a suitable container.

2. Alcohol is added in portions with stirring until a dough like mass is formed.

3. The materials are then passed through sieve # 6.

4.The resulted granules are dried at a temperature not exceeding 50ºC.

5.The granules are packed in air tight containers

Dry granulation

Procedure

1.All ingredients, except citric acid monohydrate, are dried and passed through sieve # 60.

2. The powders are thoroughly mixed and citric acid crystals are added at last (un-effloresced citric acid
contains one molecule of water of crystallization).

3.The mixture is spread in a shallow dish and placed in an oven previously heated (99- 105ºC). Upon
heating citric acid crystals, the water of crystallization effloresces and citric acid transforms to the
powder form.
4.The use of a water bath surrounding the beaker (or any container) in which the powders are stirred
is a more convenient method to prevent local overheating.
5.No stirring until the powders become moist and form doughy mass.

6.The mass is then granulated by passage through sieve # 6 and dried.

Packaging:

* Effervescent granules or powders suffer from the short shelf life, especially if they are filled into
wide-mouthed screw capped containers.

* Recently, the stability of effervescent granules and powders is greatly improved by their packing in
aluminum bags tightly closed.

Official Effervescent Salt: Sodium Phosphate NF

Dried Sodium Phosphate (Dried and Powdered) 200 g

Sodium Bicarbonate (Dry Powder) 477 g

Tartaric acid (Dry Powder) 252 g

Citric acid, (Uneffluorescence crystals) 162 g

to make 1000 g

A good working formula

Citric acid 15%

Tartaric acid 28%

Sodium bicarbonate 53%

NOTE: Dose is assumed to be a heaping teaspoon (5g). Granules should be packaged

in tight, dry wide mouth glass jars in cool place

EFFLORESCENT POWDER

Some crystalline substances liberate water of crystallization wholly or partly on exposure to

humid atmosphere or during trituration and thus become wet or liquefy. Example of such
substance include caffeine, citric acid, ferrous sulphate etc.

When some substances are exposed to air, they lose water to the atmosphere, thereby
reducing in weight. Solids that behave in this way are those with water of crystallization. The
molecules of water of crystallization are partially or completely lost to the atmosphere,
thereby making them lose their crystalline forms.

Example, Na2SO4. 10H2O loses all its water of crystallization when exposed to air; Na2CO3.
10H2O loses 9 of its molecules of water of crystallization; and FeSO4. 7H2O loses all its
molecules of water of crystallization.
Problem:Crystalline substances which during storage lose their water of crystallization and
change to powder (to be efflorescent). The liberated water converts the powder to a paste or
to a liquid.

Solution: Using the anhydrous form, and treating it in a manner similar to hygroscopic
powders

Examples: Alum- atropine sulfate- citric acid- codeine phosphate.

HYGROSCOPIC POWDERS

The powders which absorb moisture from the atmosphere are called hygroscopic powders.
But certain powders absorb moisture to such a great extent that they go into solution and are
called deliquescent powders.

Examples: NH4cl, iron, ammonium citrate, pepsin, phenobarbitone, sodium bromide and
iodide, potassium citrate, zinc chloride etc.

Problem: Absorption of moisture from air leading to partial or complete liquefaction.

Solution:

A- Applied in a granular form to decrease the exposed surface to air.

B- Packed in aluminum foil or in plastic film packets

C- Addition of light magnesium oxide to reduce the tendency to damp

D- Addition of adsorbent materials such as starch

Examples:Halide salts (ex. Sod. Iodide),Certain alkaloids (physostigmine Hcl).

EUTECTIC MIXTURES: When two or more substances are mixed together they liquefy
due to the formation of a compound which has a lower melting point than the individual
substances. Such substances are called as eutectic substances.

Examples: menthol, camphor, phenol, salol, aspirin, phenacetin, chloral hydrate etc.

Method of preparations

1.Dispense as separate set of powders with directions that one set of each kind shall be taken
as a dose.

2.An equal amount of any of inert absorbent like mgco3, light mgo2, kaolin, starch, lactose,
capo4 etc. may be mixed with eutectic substance and then blended together lightly with a
spatula on a sheet of paper. When in addition to liquefying substances, other ingredients are
also present, liquefying substances should first be triturated together to form the eutectic
mixture. Then the reaming ingredients of the prescription are incorporated and mixed
together.
EXAMPLE: Dispense 50g of the following insufflations.

Menthol 5.0g

Camphor 5.0g

NH4cl 30.0g

Light Mgco3 60.0g

Make insufflations.

Direction: to be used as directed.

Method: Separately powder each ingredient and weigh required quantity of menthol,
camphor and ammonium chloride. Mix them in ascending order of their weight in a mortar to
form a liquid. Add light mgco3 to make a free flowing powder. Pass the powder through
number 85 sieve and dispense the powder in an air tight container.

SELECTION OF PAPER

1.Hygroscopic or deliquescent - use water proof or waxed paper.

2.Powders containing volatile components - should be wrapped in waxed or in glassine

papers.

3.Powders containing neither volatile components nor ingredients adversely affected by air or
moisture are usually be wrapped in white papers.

Papers may be

1.Simple bond papers

2.Vegetable parchment

3.Glassine, a glazed, transparent paper

4.Waxed paper, a transparent waterproof paper

Packing of Powders: Powder papers packing sizes

2 3/4 x 3 3/4 inches,

3 x 4 1/2 inches,

3 3/4 x 5 inches and

4 1/2 x 6 inches
 UNIT 3:

A.LIQUID DOSAGE FORMS

Liquid dose forms consist of one or more active ingredients in a liquid vehicle. These dose
forms can be divided into two major categories:

(1) Solutions, in which active ingredients are dissolved in the liquid vehicle; and (2)
Dispersions, in which undissolved ingredients are dispersed throughout a liquid vehicle.

Advantages

Its action is rapid.

The consumption is easy.
The products like antacids and adsorbents are much effective in this dosage form.
Ease of swallowing and of adjusting the dose.

A liquid dose can be easily adjusted, whereas tablets or capsules cannot always be divided as
easily.

For the patient, taste preference may be either an advantage.

Disadvantages

Children’s medication is often flavored in the most palatable way possible to improve
compliance.

Liquid dose forms are often less stable than their solid counterparts, and care should be taken
to monitor storage conditions of the liquid dose forms, to rotate stock, and to check expiration
dates often

Less dosage accuracy.

Preservation is main problem.
Transportation is main difficult.
CLASIFICATION OF LIQUID DOSAGE FORMS

Liquid dosage form classified into two categories as follows:

A. Monophasic liquid dosage form

B. Biphasic liquid dosage form

A. Monophasic liquid dosage form

Monophasic liquid dosage form further classified into two types

1. Monophasic liquid dosage form for Internal use

Monophasic liquid dosage form for Internal use further classified into four types
B. Biphasic liquid dosage form

Biphasic liquid dosage form further classified into two types as follows

SYRUPS

Syrup is a concentrated or nearly saturated solution of sucrose in distilled water. The

concentration of sugar in syrups is 66.7% w/w. The syrup is a sweet viscous preparation. The
syrups which contain medicinal substance are called “medicated syrups’’. The syrups
containing flavoured substances are “flavoured syrups’’.

Advantages of syrups

1. Syrups retards oxidation because it is partly hydrolyzed into reducing sugar such as
dextrose and levulose.

2.It prevents decomposition of many vegetable substances. Syrups have high osmotic pressure
which prevents the growth of bacteria, fungi and molds which are the chief causes of
decomposition in solutions of vegetable matter.

3.They are palatable. Due to the sweetness of sugar it is a valuable vehicle for the
administration of unpalatable substances.

Disadvantages of Syrups

1. Delayed onset of action because absorption takes time.

2. Not suitable in emergency and for unconscious patients.

3. Not convenient for a patient with a gastrointestinal disorder such as diarrhea, constipation,
ulceration, and hyperacidity in stomach.

4. Cannot avoid first pass metabolism.

Types of syrups

Syrups are classified into three types as follows

1. Simple syrup–concentrated solution of sucrose in purified water alone.

2. Medicated syrup–aqueous solution of sucrose containing other substances as

polyols(glycerin and sorbitol)

3. Non‐medicated/Flavored syrup–contained various aromatic and pleasantly flavored

substances and is intended as a vehicle or flavor for preparations.

Uses of Syrups

1. Due to sweetness, can mask the taste of salty and bitter drugs and
therefore serve as pleasant tasting vehicle

2. Used as vehicle for pediatric use due to to their high viscosity and
the “smoothness” and mouth feel qualities.

3. Due to the wide variety of flavors of syrups such as orange, lemon, peppermint, these are
widely acceptable.

Components of Syrups

The major components of syrups are as follows:

Purified water: Purified water is water that has been mechanically filtered or processed to
remove impurities and make it suitable for use in syrups.

Sugar (sucrose) or sugar substitutes (artificial sweeteners):

Traditionally syrups are composed of sucrose (usually between 60 and 80%) and purified
water.

Due to the inherent sweetness and moderately high viscosity of these systems, the addition of
other sweetening agents and viscosity-modifying agents is not required.

In addition, the high concentration of sucrose and associated unavailability of water (termed
low water activity) ensures that the addition of preservatives is not required.

As the concentration of sucrose is reduced from the upper limit (e.g. through dilution), the
addition of preservatives may be required.

In some formulations, other non-sucrose bases may replace traditional syrup. One of the most
popular is Sorbitol Solution USP, which contains 64% w/w sorbitol, although other
alternatives are available that are based on mixtures of sorbitol and glycerin.

These non-sucrose bases may be mixed with traditional syrups, if required, in the formulation
of oral syrups that possess a low concentration of sucrose in comparison to traditional syrups.

More recently, many products have been formulated as medicated sugar-free syrups due to
the glycogenetic and cariogenic properties of sucrose.
For the afore-mentioned reasons, all medicinal products designed for administration to
children and to diabetic patients must be sugar-free. Syrup substitutes must therefore provide
an equivalent sweetness, viscosity and preservation to the original syrups. To achieve these
properties artificial sweeteners (typically saccharin sodium, aspartame), non-glycogenetic
viscosity modifiers (e.g. methylcellulose, hydroxyethylcellulose) and preservatives (e.g.
sodium benzoate, benzoic acid and parahydroxybenzoate esters) are included.

Preservatives:

As highlighted above, preservatives are not required in traditional syrups containing high
concentrations of sucrose.

Conversely, in sugar-free syrups, syrups in which sucrose has been substituted at least in part
by polyhydric alcohol and in traditional syrups that contain lower concentrations of sucrose,
the addition of preservatives is required.

Typical examples of commonly used preservatives include: – Mixtures of

parahydroxybenzoate esters (usually methylhydroxybenzoate and propylhydroxybenzoate in
a ratio of 9:1).

The typical concentration range is 0.1–0.2% w/v. It is important to note that the preservative
efficacy of these preservatives may be decreased in the presence of hydrophilic polymers
(generally employed to enhance viscosity), due to an interaction of the preservative with the
polymer.

This effect is negated by increasing the overall preservative concentration. Other

preservatives that are employed include benzoic acid (0.1–0.2%) or sodium benzoate (0.1–
0.2%).

Flavours:

These are employed whenever the unpalatable taste of a therapeutic agent is apparent, even in
the presence of the sweetening agents.

The flavours may be of natural origin (e.g. peppermint, lemon, herbs and spices) and are
available as oils, extracts, spirits or aqueous solutions.

Alternatively, a wide range of synthetic flavours are available that offer advantages over their
natural counterparts in terms of purity, availability, stability and solubility.

Certain flavours are also associated with a (mild) therapeutic activity. For example, many
antacids contain mint due to the carminative properties of this ingredient.

Alternatively other flavours offer a taste-masking effect by eliciting a mild local anaesthetic
effect on the taste receptors. Examples of flavours in this category include peppermint oil,
chloroform and menthol. The concentration of flavour in oral syrups is that which is required
to provide the required degree of taste-masking effectively.

Colours:

These are generally natural or synthetic watersoluble, photo-stable ingredients that are
selected according to the flavour of the preparation. For example, mint-flavoured
formulations are commonly a green colour, whereas in banana-flavoured solutions a yellow
colour is commonly employed. Such ingredients must not chemically or physically interact
with the other components of the formulation.

Preparation of the syrup

There are four methods. Based on the physical and chemical properties on the ingredients, the
choice of the method is selected.

1. Solution with heat: The temperature of purified water is increased to 80 to 85 C and then
taken off from the heat source. Then add sucrose and shake it thoroughly. Those ingredients
which are resistant to high temperatures are added. Those substances that are heat sensitive
and volatile agents are added after the solution attain the room temperature. But during
heating, the sucrose gets hydrolysed, results in the formation of dextrose and fructose, these
two sugars together called as invert sugar and the process is known as inversion. This
reaction takes place more rapidly in presence of acids. The inversion leads to darkening of the
solution.

Examples : Acacia syrup, NF; Cocoa Syrup, NF

2. Agitation without heat: This is a simple technique in which a vessel is taken generally
made up of stainless steel or glass. The vessel should be larger than the desired volume of
syrup required. Then the ingredients according to the formulation are added to watr and
mixed. It is better to dissolve solid ingredients in the water first and then to add them to
syrup. This results in easy mixing as sugar solution generally retards mixing.

Examples:Ferrous Sulfate Syrup, Ephedrine Sulfate, Citric acid Syrup, and Glycyrrhiza
Syrup.

3. Addition of sucrose to liquid medicament: This method is generally used for fluid
extracts. But those substances which are soluble in alcohol will precipitate out as soon as the
addition of water. An alternation is to first dissolve all the ingredients in water. Now after
sometime all the precipitates formed are filtered out. Now add sucrose. But this method is of
no use if the precipitates formed has active ingredients.

Examples:Senna Syrup, NF and Cherry Syrup.

4. Percolation method: As the name suggest, the principle of percolation is used. A sucrose
bed is prepared and then water or vehicle containing therapeutic agent is passed. Here the
 sucrose bed should be coarse and shape of percolator must be cylindrical or cone
shapped.Sucrose syrups are replaced by agents like sorbital solution or mixture of sorbital
and glycerin. Sorbital is osmotic laxative and so it must be administered within the limits.
Sorbital solution contains about 64% of sorbital.

Example:Tolu Balsam syrup -flavor for cough syrup.

Storage of syrup:Stored in narrow mouthed, well closed, amber color or plain bottle.

Instruction: KEEP IT IN A COOL PLACE.

ELIXIRS

The elixirs are definesas a clear, sweetened hydroalcohol liquids intended for oral use
containing flavoring substances or active medicinal agents.

Their primary solvents are alcohol and water, with glycerin, sorbitol and syrup sometimes as
an additional solvent and/or sweetening agents.

They are prepared by simple solution or admixture of the several ingredients.

They are used either as vehicles or for the therapeutic effect of the medicinal substances that
they contain.

Advantages

1. Easy to swallow than tablets or capsule.

2. It tastes good.

3. Clear solution, no need to be shuffled again.

Disadvantages

1. Alcohol is not good for children.

2. Because they contain volatile materials, it must be stored in a watertight screw-top jar and
away from sources of ignition.

Types

Elixir are classified into two types as follows

1. Non-medicated elixirs:

They are used as solvents or vehicles for the preparation of medicated elixirs: aromatic elixirs (USP),
isoalcoholic elixirs (NF), or compound benzaldehyde elixirs (NF). Active ingredient
dissolved in a solution that contains 15 to 50% by volume of ethyl alcohol.
2. Medicated elixirs:

Antihistaminic elixirs: used against allergy: chlorampheniramine maleate elixirs (USP),

diphenhydramine HCl elixirs.

Sedative and hypnotic elixirs: sedatives induce drowsiness, and hypnotics induce sleep:
pediatric chloral hydrate elixirs.

Expectorant: used to facilitate productive cough (cough with sputum): terpin hydrate elixirs.

Miscellaneous: acetaminophen (paracetamol) elixirs, which are used as analgesics.

Composition

An elixir is a hydro-alcoholic solution of at least one active ingredient. The alcohol is mainly
used to:

Solubilize the active ingredient(s) and some excipients

Retard the crystallization of sugar

Preserve the finished product

Provide sharpness to the taste

Aid in masking the unpleasant taste of the active ingredient(s)

Enhance the flavor.

The lowest alcoholic quantity that will dissolve completely the active ingredient(s) and give a
clear solution is generally chosen. High concentrations of alcohol give burning taste to the
final product.

An elixir may also contain the following excipients:

• Sugar and/or sugar substitutes like the sugar polyolsglycerol and sorbitol.
• Preservatives like parabens and benzoates and antioxidants like butylated
hydroxytoluene (BHT) and sodium metabisulfite.
• Buffering agents
• Chelating agents like sodium ethylenediaminetetraacetic acid (EDTA)
• Flavoring agents and flavor enhancers
• Coloring agents.

Methods of Preparations

Simple solution is the general process employed in preparing elixirs. Many are prepared,
however, by adding the medicinal substances directly to aromatic elixir, which is an elixir-
 base. While elixirs are very simple to mix, it should be noted that most elixirs are very
difficult to filter, and since most elixirs require filtration, suction filtration is the
recommended method.

USES: Used internally. Their uses vary according to their ingredients.

EXAMPLE: Elixir of Terpin Hydrate

Storage:Stored in narrow mouthed, well closed, amber color or plain bottle.

Instruction: KEEP IT IN A COOL PLACE.

Linctus

Linctuses are viscous, liquid, oral preparations that are usually prescribed for the
relief of cough.

They contain medicaments which have demulcent (which soothes the inflamed mucous
membrane preventing contact with air in the surroundings), sedative or expectorant action.
The viscous vehicle soothes the sore membrane of the throat.

The usual dose is 5 ml. Linctuses should be taken in small doses, sipped and swallowed
slowly without diluting it with water in order to have the maximum and prolonged effect of
medicaments.

Simple Syrup is generally used as a vehicle. For diabetic patients Sorbitol solution is used
instead of Simple Syrup.

Linctuses are viscous preparations that contain the therapeutic agent dissolved in a vehicle
composed of a high percentage of sucrose and, if required, other sweetening agents. These
formulations are administered

orally and are primarily employed for the treatment of cough, due to their soothing actions on
the inflamed mucous membranes.

Linctuses may also be formulated as sugar-free alternatives in which sucrose is replaced by

sorbitol and the required concentration of sweetening agent.

Linctuses are viscous, liquid, oral preparations that are usually prescribed for the relief of cough.

Example-Codeine Linctus, Paediatric B.P.C.

Formula

Ingredients Quantity Use

Codeine Phosphate 3g Active ingredient (coughsuppressant)
Lemon Syrup 200ml Flavor
Benzoic acid solution 20ml Preservative
Chloroform Spirit 20ml Preservative
 Purified Water 20ml Solvent for codeine phosphate
Compound Tartrazine 10ml Color
Solution
Syrup, up to 1000ml Vehicle (viscous and sweet)

Method of preparation:

(i) Codeine phosphate is weighed and taken in a conical flask.

(ii) Water is added to the flask, heated gently to dissolve.

(iii) Color, benzoic acid solution and chloroform spirit are added one at a time and mixed
thoroughly after each addition.

(iv)Lemon syrup is added and mixed. Syrup is added and mixed.

Excipients used in Linctuses

1.Vehicle:simple syrup is generally used as a vehicle for most of the Linctuses. Suryp tolu is
prepared in certain cases because of aromatic odour and flavour. Moreover, it is believed to
have a mild expectorant action. Invert syrup, glycerol and sorbitol solution are also used as a
vehicle in certain elixirs.

2.Adjuncts

A.Chemical stabilizers: the majority of linctuses are stable because simple syrup is used as a
vehicle.

B.Colouringagents: Coal tar dyes are commonly used as a colouring agents in elixirs.
Among them, compound tatrazine solution is most popular colouring agent.

C.Flavouring agents: Lemon syrup and black current syrup are commonly used as
flavouring agents. Oxymel and benzaldehyde spirit (almond like flavour) are also used as
flavouring agent in certain elixirs.

D.Preservatives: When syrup is used as vehicle, no Preservative is needed for the

Preservation of linctuses due to high osmotic pressure of syrup. Syrup tolu has a mild
antibacterial action due to benzoic acid and Cinnamic acid present in it. The linctuses which
are made in sorbitol solution or diluted with water are preserved by adding spirit chloroform
and benzoic acid.

Storage: Linctuses are supplied in well filled, well closed airtight glass bottles having screw
caps. Linctuses are stored in a cool place, protected from light.

Container: Codeine phosphate degrades in light so an amber color bottle is used.

Label: “To be sipped and swallowed slowly without adding water.”

Use: Linctuses are used for treatment of cough.

 DROPS

A Liquid preparation in which the quantity to be used at any one time is so small it is
measured as a number of drops (Example in small pipette).

Drops may comprise an oral preparation(Usually Paeditric),or may be intended for

introduction into the nose,ear or eye;the title of the products is amended accordingly.

ORAL DROPS

Oral drops is a liquid preparation for oral use that are intended to be administrated in less
volumes with the aid of suitable measuring devices. Theses may be solutions, suspensions or
emulsions.

LINIMENTS

Liniments are liquid or semi-liquid or semi-solid preparations intended for application to the
skin. The linements are usually applied to the skin with friction and rubbing of the skin.

They may be alcoholic or oily solutions or emulsions. Alcohol helps in penetration of drug into
the skin. In oily liniment arachis oil is generally used, it helps in spreading the liniment on the
skin.

Most of them are massaged into the skin (counter irritant or stimulating type).

Generally liniments contain medicaments possessing analgesic (reduces pain), rubefacient

(produce local reddening of skin when rubbed) and counter irritant (counters strong irritation).

The liniments should not be applied on broken skin, because it will produce excessive irritation.

Storage: Stored in fluted bottle (to indicate an external preparation), well-closed air tight
container. It must be stored in a cool place, because it contains volatile ingredients.

Instruction: FOR EXTERNAL USE ONLY

“Shake the bottle before use.”

“Not to be applied to open wound or broken skin”.

Example: Turpentine liniment

Rx Soft soap 8g

Camphor 5g

Turpentine oil 65ml

Purified water, q.s. 100ml

 Procedure:

(i) In a dry beaker, camphor is dissolved in turpentine oil.

(ii) Soft soap is dissolved in a mortar with small amount of purified water. The oil solution is
added in small amount to the soap solution and mixed thoroughly until a smooth creamy
emulsion is formed.

(iii) Sufficient purified water is added to the creamy emulsion and mixed thoroughly.

(iv) The preparation is transferred to a bottle, polished and labeled.

Additives in linements

Liniments are alcoholic or oil-based solutions or emulsions formulations, containing

therapeutic active agents mainly used for external application. These formulations are also
known as embrocations because they are rubbed onto the affected area with friction.
Liniments should not be applied to skin that is bruised or broken. Presence of the oil base or
soap base providing ease of application and massage on affected areas. Alcoholic liniments
are generally used due to their various characteristics property such as excellent rubefacient,
counterirritant, mildly astringent and penetrating effects. At the time of massage, oily
liniments are more useful and exhibit milder action. Fixed oils are thick, viscous liquids and
contain unsaturated fatty acids which cause good penetration into the skin.

Example:

1.Castor oil: Used externally as an emollient,Provide soothing to the skin,Stimulates water

secretion in the intestine, Stimulates colonic motility and Used in constipation.

2.Cotton seed oil: Used in the manufacture of soaps, oleomargarine, lard substitutes,glycerin,
lubricants and cosmetics and Used in food.

3.Peanut oil: It also is used for ointments, plasters, and soaps, as a subsstitute for olive
oil,Used as a massage oil and Used as a tasting agents in the formulations.

4.Sesame oil: Used as solvent and vehicle in official injections,Used medicinally and for
food.Used in the manufacture of cosmetics, iodized oil, liniments and ointments and Show
good permeation effects.

5.Oleic acid: Major component of soap as an emulsifying agent and Used as an emulsifying
or solubilizing agent in aerosol products.

6.Ammonia solution: Provide alkaline medium and Used for ‘‘flavor’’ enhancement and as a
‘‘Pharmaceutical aid".

LOTIONS

Lotions are liquid preparations for external application without friction.

The lotion is soaked in a absorbent cotton or gauze and are applied on the skin
Lotions may be used for local cooling, soothing, protective or antiseptic purposes.

Examples: Calamine lotion (for preparation see Practical note), Salicylic acid lotion BP

Calamine 15.0g

Zinc oxide 5.0g

Bentonite 3.og

Sodium citrate 0.5g

Liquefied phenol 0.5ml

Glycerin 5.0ml

Rose water sufficient to produce 100ml

Method: Dissolve sodium citrate in rose water. Triturate the calamine, zinc oxide and
bentonite with a solution of sodium citrate. Add the liquefied phenol. Add the glycerin. Add
purified water in sufficient quantity to produce the required volume.Tranfer the lotion to a
bottle,cork,label and dispence.

Container: Dispensed in a colored, fluted bottle.

Instruction: FOR EXTERNAL USE ONLY

“Shake well before use”–because on long standing some ingredient may separate
out.

Additives in lotions

Lotions are usually suspensions of solids in an aqueous medium. It is a low to medium

viscosity topical preparation intended for application to unbroken skin. They are thicker and
emollient in nature in comparison to solution. They are usually oil mixed with water, and
more often than not have less alcohol than solutions. The main advantages of this delivery
system are avoidance of first pass metabolism, easy to apply, improved patient compliance,
improved physio-logical and pharmacological response, avoidance of gastro- intestinal
incompatibility and ability to easily terminate medications when needed, However, various
disadvantages are associated with these systems such as skin irritation or contact dermatitis,
which may occur due to the drug and additives, poor permeability of some drugs, chances of
allergic reactions and sometime drugs are not absorbed through the skin due to larger particle
size.

Example

1.Bentonite:High viscosity and thixotropy,High vitrification temperature, High specific

surface and Used as a bulk laxative,Used as a base for many dermatologic formulas,Used in
battlefield wound dressings.
2.Sodium carboxymethylcellulose: Used as food additive,Used as lubricant in eye drops,Used
in pharmaceuticals as a thickening agent.

3.Alcohol: Provide drying and cooling effect of a lotion and Used as an antiseptic.

4.Glycerin: Improving smoothness, providing lubrication and Used as humectants.

5.Preservative: Ester of parahydroxy benzoic acid, Chlorocresol, Phenoxyethanol, Quaternary

ammonium compound and Phenyl mercuric nitrate act as preservative.

GARGLES
Gargles as a class of preparations are aqueous solutions employed form treating the pharynx
and nasopharynx by forcing air from the lungs through the gargle which is held in the throat.
Many mouth washes are used as gargles either as is or diluted with water. Many gargles are
diluted with water prior to its use.Constituents: phenol &thymol,potassium chlorate € Ex:
phenol, gargle,potassium chlorate and phenol gargle.

Preparation: NF Gargle is also known as Alkline Aromatic Solution NF II, Liquor

Aromaticus Alkalinus, Liquor Antisepticus Alkalinus NF IV, and Alkaline Antiseptic
Solution.

Formula:

Potassium Bicarbonate 20 g

Sodium Borate 20 g

Thymol 0.5 g

Eucalyptol 1.0 ml

Methyl salicylate 0.5 ml

Amaranth Solution 14 ml

Alcohol 50 ml

Glycerin 100 ml

Purified Water, q.s. ___________

To make 1000 ml

Dissolve the potassium bicarbonate and sodium borate in 100ml purified water, add the
glycerin when effervescence has ceased, add the mixture to 500ml purified water. Dissolve
the other ingredients in the alcohol, and add the solution of salts to the alcoholic solution
with agitation. Then add sufficient quantity of purified water to make the product measure
1000ml. Allow the mixture to stand, with occasional shaking during 24 hours. Filter using
talc, if necessary to produce a clear solution.
Uses: Antibacterial mouthwash, nasal douche and throat gargle which is approximately
isotonic with body fluids and therefore non-irritant to the mucous membranes. For oral use
undiluted; dental spray diluted with 5 volumes of water.

Container: gargles are dispensed in clear, flutted glass bottle closed with plastic screw cap.

Labeling: The container should be labelled “ FOR EXTERNAL USE ONLY”

The purpose of their application may be: Disinfection Pain-killing Deodoration Cleaning, etc.

Excipients: Gargles may contain excipients to adjust the pH which, as far as possible, is
neutral. Many gargles must be diluted with water prior use. After the use of gargles patients
should not wash their teeth, rinse their mouth cavity, drink or eat.

THROAT PAINTS

Throat paints are viscous liquid preparations used for mouth and throat infections.Glycerin is
commonly used as a base because being viscous.It adheres to mucous membrane for a long
period. It also provides a sweet taste to the preparation. The commonly used throat paints are
boroglycerin, phenol glycerin, tannin acid glycerin, compound iodine paint (mandl’s paint).
Constituents: glycerine is commonly used as base because of its viscous nature
Eg:Mandles paint
General Preparation
Example: Prepare and dispense 50.0ml of iodine paint compound (Mandl’s paint) B.P.C

IODINE PAINT COMPOUND (MANDL’S PAINT) B.P.C

Potassium iodide 25.0 g

Iodine 12.5g

Alcohol 90% 40ml

Water 25.0ml

Peppermint oil 4.0ml

Glycerin to produce 1000ml

Method: Dissolve the potassium iodide in water. Add the iodine and stir until completely
dissolved. Dissolve peppermint oil in alcohol 90% in a small container and transfer it into
iodine solution. Mix well. Add glycerin and mix thoroughly. Transfer the paint into a
measure. Add more of glycerin to make the required volume. Transfer the preparation into a
well closed container, label and dispense.

Containers: Throat paints should be dispensed in airtight, coloured fluted bottle in order to
distinguish them from preparations meant for internal use. Glass stoppers are generally used
in such bottles.

Labelling: The container should be labelled “for external use only”

Storage: the throat paints should be stored in airtight container and in cool place.

MOUTH WASHES

Mouth wash is a medicated liquid used for cleaning the oral cavity and treating mucous
membranes of the mouth and it may contribute to surface softening and increased wear of
dental resins and composite materials.

Advantages

can boost your oral health.

may prevent plaque from building up.

Rinses with fluoride can help preventcavities.

Fluoride protects against tooth decay(cavities).

Mouthwash can help you target plaque.

Prevents dry mouth.

Disadvantages

Some mouth rinses contain high levels of alcohol—ranging from 18 to 26 percent.

This may produce aburning sensation in the cheeks, teeth, and gums.

Types

There are four types of Mouthwash as following:

1.Fluoride mouthwashes contain sodiumfluoride which helps to strengthen theteeth as well as

adding extra protectionagainst tooth decay.cosmetic mouthwashes do not offer the same
protection as other types and are used more as a means of disguising bad breath(halitosis).

2.Antiseptic mouthwashes contain chlorhexidinegluconate - a chemical which stops the

growth ofbacteria and is suitable for people with a mouthinfection.

3. Natural mouthwashes are alcohol-free (and contain nofluoride) and work in much the same
way as conventional mouthwashes. They can also treat a mouth infection or injury.

4. Total care mouthwashes contain anti-bacterial ingredientswhich help to reduce the buildup
of plaque and prevent gum disease.

Genral Preparation

Example Prepare and dispense 50.0ml of compound sodium chloride, mouth wash B.P.C

COMPOUND SODIUM CHLORIDE MOUTH WASH B.P.C

Sodium chloride 15g

Sodium bicarbonate 10g

Peppermint water to produce 1000ml

Method: Dissolve the weighed quantity of sodium chloride and sodium bicarbonate in 3/4th of
the peppermint water. Add more of peppermint water to produce the required volume.
Transfer to a bottle, label and dispense.

Container: Mouthwashes are dispensed in wide mouthed bottle.

Labeling: The label should clearly indicate the proper directions for diluting the mouthwash
before use and also apply the secondary label, ‘’For external use only’’

NASAL SPRAYS

Nasal sprays are used to reduce nasal congestion and to treat infections. The main aim of
nasal spray is to retain the nasal solution in the droplet from in the nasal track. For this
purpose, the nasal solution is sprayed in the form of coarse droplets by using scent spry type
of atomiser or a plastic squeeze bottle. The nasal spray should be isotonic and buffered at p h
6.2. They may contain antibiotics and antihistamines

Containers: nasal sprays are stored in small coloured , fluted glass bottles. Plastic squeeze
bottles automiser or pressurized aerosols are most suitable for administration

Storage: nasal sprays should be stored in well filled air tight containers. This should be
protected from light.

Example: prepare and dispense 100ml of nasal spray

Methanol ----------- 2.0gms

Camphor -------------- 2.0 gms

thymol ---------------- 2.0gms

Eucalyptus oil ------------- 5ml

Liquid paraffin ------------ 100ml

Method: triturate menthol, camphor and thymol in a dry mortar. Add the eucalyptus oil.
Transfer to dry measure. Rinse the mortar with liquid paraffin and add more of liquid paraffin
to make required volume, Transfer to the container, label and dispense.

EAR DROPS

These are solutions of drops that are instilled into the ear with a dropper. The is generally
prepared in water, glycerin, propylene glycol or dilute alcohol. However, vehicle like
glycerin and propylene glycol are preferred. These are generally used for cleaning the ear,
softening the wax and for treating the mild infection.
Containers: Ear drops are dispensed in coloured, fluted glass bottles with a dropper in the
cap. Ear drops are also dispensed in suitable plastic containers.

Labelling: the label should state, “for external use only” and “store in cool place”.

Example: prepare and dispense 25.0 ml of soda glycerin.

sodium bicarbonate---------5g

glycerin------------------------- 30ml

purified water, to produce----100ml

prepare ear drops

Direction: place 2-3 drops in each ear as directed.

Uses: it is to relieve itching in the ear and soften the wax.

NASAL DROPS

These are aqueous solutions of drops that are instilled into the nose with dropper. The oily
vehicle is not used nowadays because oily drops inhibit the movement of cilia in the nasal
mucosa and if used for long periods, may reach the lungs and cause lipoid pneumonia.

Nasal drops should be isotonic with 0.9% sodium chloride having neutral ph and viscosity
similar to nasal secretions by using 0.5% methyl cellulose. The buffering capacity of nasal
mucosa is quite low and strong alkali solutions can cause considerable damage to cilia. To
prevent this, it is advisable to use a phosphate buffer of ph6.5 as a vehicle. Nasal preparation
must not interfere with the cleansing action of epithelial cilia of nasal mucosa.

Containers: nasal drops are dispensed in coloured fluted bottles fitted with a dropper or in a
suitable plastic container.

Labelling: the container should be labeled “for external use only”.

Storage: nasal drops should be stored in a cool place.

Example: prepare and dispense 10ml of ephedrine nasal drops b.p.c

Ephedrine hydrochloride 0.5g

Chlorobutol 0.5g

Nacl 0.5g

Water to produce 1000ml

Method: dissolve the ephedrine Hcl, chlorobutol, and nacl in warm water. Cool, filter if
necessary and make to volume through the filter. Transfer the nasal drops to the container,
label and dispense.
SUSPENSIONS

These are biphasic liquid dosage form of medicament in which finely divided solid particles
which are dispersed in a liquid or a semi solid vehicle. Here the solid particle acts as a
dispersed phase where liquid vehicle acts as continuous phase. Suspensions are generally
consumed orally or by parental route. They are also meant for external use.

Advantages

i) It is easy to dispense unstable or degradable drugs in solution form.

ii) Suspension is the only choice if the drug is not soluble in water and non-aqueous solvent is
not acceptable, e.g., corticosteroids suspension.

iii) Suspension is most suitable for drugs having unpleasant taste and Odour e.g.,
Chloramphenical palmitate (bitter taste).

iv) The insoluble solids act as a reservoir and continuously supply the drug into solution,
which is absorbed over a long period e.g., Protamine zinc-Insulin.

v) Drug in suspension exhibits a higher rate of bioavailability compared to the same drug of
equivalent dose formulated in tablets or capsules. This is due to larger surface area and high
dissolution, e.g., antacid suspension.

Disadvantages

1. Sedimentation of solids occasionally gives poor form of product. It may lead to caking
(formation of compact mass), which is difficult to dispense.

2. Dose precision cannot be achieved unless suspensions are packed in unit dosage forms.

3. Sometimes microbial contamination takes place if preservation not added in accurate

proportion.

4. A suspension being a bulky product, transportation cost is high.

Applications

1. Suspension is usually applicable for drug which is insoluble or poorly soluble.

E.g.Prednisolone suspension· to prevent degradation of drug or to improve stability of drug.

E.g. Oxytetracycline suspension· To mask the taste of of drug can be formulated for topical
application

E.g. Calamine lotion improve stability of drug

E.g. Oxytetracycline suspension· To mask the taste of Suspension can be formulated for parentral
application in order to control rate of drug absorption.
 2. Vaccines as a immunizing agent are often formulated assuspension.E.g. Cholera vaccine· X-ray
contrast agent are also formulated assuspension.E.g. Barium sulphate for examination of alimentary
tract.

3. Suspension is usually applicable for drug which is insoluble (or) poorly soluble.

E.g. Prednisolonesuspension

4. To prevent degradation of drug or to improve stability of drug.

E.g. Oxy tetracycline suspension

5. To mask the taste of bitter of unpleasant drug

E.g. Chloramphenicol palmitate suspension

6.Suspension of drug can be formulated for topical application.

E.g. Calamine lotion.

7. Suspension can be formulated for parentral application in order to control rate of drug
absorption

E.g. penicillin procaine

8. Vaccines as a immunizing agent are often formulated as suspension.

E.g. Cholera vaccine

9. X-ray contrast agent are also formulated as suspension.

E.g.Barium sulphate for examination of alimentary tract.

Properties of a good suspension

1. After shaking, the medicament stays in suspension long enough for removal of the correct
dose from oral products and the correct proportion to active ingredients from external
preparations.

2.The sediment produced on standing is easily redispersed. Deflocculated system produces

cake, which is not redispersible. So the system must be partially flocculated with the help of
flocculating agents.

3. It is easily pourable.

4. It is comparatively free from large particles, which gives a bad appearance, gives a gritty
taste to oral preparation and if it is an external product produces irritation on the skin.

General method of preparation

(a) The poorly wettable solids are taken in a mortar and triturated with the wetting agents.
(b) Gradually vehicle is added to it.

(c) The liquid preparation is transferred to a bottle, capped, polished and labeled.

Container: For oral preparation: Narrow mouthed, screw capped, colourless, plain bottle.

For external preparation: Narrow mouthed, screw capped, colorless, fluted bottle.

Label: The ink used in the label Black.

Special instruction(s): SHAKE WELL BEFORE USE

For external preparation(s) FOR EXTERNAL USE ONLY

Method of preparation:

(a) Sulphurated potash is dissolved in ½ of the vehicle.

(b) Zinc sulfate is dissolved in another ½ of the vehicle.

(c) Sulphurated potash solution is added to the zinc sulfate solution slowly with constant
stirring.

(d) The suspension is transferred to a tared bottle and the volume is made up with the
vehicle.

Classification of Suspensions

Based on Size of Solid Particles Suspensions are classified into two types as follows:

a. Flocculated Suspensions and b. Deflocculated Suspensions

Flocculated Suspensions

In flocculated suspension, formed flocs (loose aggregates) will cause increase in

sedimentation rate due to increase in size of sedimenting particles.

Hence, flocculated suspensions sediment more rapidly.

Here, the sedimentation depends not only on the size of the flocs but also on the porosity of
flocs.
Deflocculated Suspensions

➢ In deflocculated suspension, individual particles are settling.

➢ Rate of sedimentation is slow , which prevents entrapping of liquid medium which
makes it difficult to re-disperse by agitation.
➢ This phenomenon called ‘caking’ or ‘claying’.􀂾In deflocculated suspension larger
particles settle fast and smaller remain in supernatant liquid so supernatant appears
cloudy.

Physical stability of Suspensions

Physical stability is defined as the condition in which the particles remain uniformly
distributed throughout the dispersion without any signs of sedimentation. It is difficult to
achieve in this case it is restated as – if the particles settle it can be redisperse on moderate
shaking.therefore, the extent of sedimentation expressed by several methods.

Sedimentation Method:

Two parameters are studied for determination of sedimentation.

➢ Sedimentation volume
➢ Degree of flocculation.
Sedimentation Volume: The suspension formulation(50mL) was poured separately
into100mL measuring cylinder and sedimentation volume wasread after1,2,3and7days, and
thereafter at weekly intervals for12weeks.
 Triplicate results were obtained for each formulation.

Sedimentation volume was calculated according to the equation:

F = Vu/Vo

Where, F = sedimentation volume,

Vu= ultimate height of sediment

And Vo= initial height of total suspension

Sedimentation volume is a ratio of the final or ultimate volume of sediment (Vu), to the original volume of
sediment (Vo), before settling. Some time µF is represented as µVs and as expressed as percentage. Similarly
when a measuring cylinder is used to measure the volume.

F= Hu/ Ho

Where, Hu= final or ultimate height of sediment.

Ho= original height of suspension before settling.

Sedimentation volume can have values ranging from less than 1 to greater than1;

F is normally less than 1. F=1, such product is said to be in flocculation equilibrium. And show no clear
Supernatan on standing Sedimentation volume (F ¥) for deflocculated suspension.

F ¥ = V¥/ Vo

Where, F ¥ = sedimentation volume of deflocculated suspension

V¥ = sediment volume of completely deflocculated suspension

Vo = original volume of suspension

Suspensions quantified by sedimentation volume(f)

Degree of flocculation (β) :

It is the ratio of the sedimentation volume of the flocculated suspension ,F , to the

sedimentation volume of the deflocculated suspension, F∞

ß = F / Fo

(vu/v0) flocculated
ß=
(vu/v0) deflocculated

The minimum value of ß is 1,when flocculated suspension sedimentation volume is equal to

the sedimentation volume of deflocculated suspension.

Container: For external preparation: Narrow mouthed, screw capped, colourless, fluted
bottle.
Label: The ink used in the label Black.

Special instruction(s):

SHAKE WELL BEFORE USE, KEEP IN A DARK CUPBOARD

For external preparation(s) FOR EXTERNAL USE ONLY

EMULSIONS

An emulsion is a biphasic liquid preparation containing two immiscible liquid phases, one of
which is dispersed as fine globules (or droplets) in another. The fine globules are called
dispersed phase and the other is called continuous phase.Emulsions are unstable so the
system is stabilized by addition of a third agent. It is called emulsifier or emulsifying agent or
emulgent.

Advantages

- Unpalatable oils can be administered in palatable form.

- Unpalatable oil-soluble drugs can be administered in palatable form.

- The aqueous phase is easily flavoured.

- The oily sensation is easily removed.

- The rate of absorption is increased.

- It is possible to include two incompatible ingredients, one in each phase

of the emulsion.

Disadvantages

- Preparation needs to be shaken well before use.

- A measuring device is needed for administration.

- A degree of technical accuracy is needed to measure a dose.

- Storage conditions may affect stability.

-Bulky, difficult to transport and prone to container breakages.

-Liable to microbial contamination which can lead to cracking.

Properties of emulsions

Emulsions usually appear cloudy or white because light is scattered off the phase inter phases
between the components in the mixture.

If all of the light is scattered equally, the emulsion will appear white.
Dilute emulsions may appear slightly blue because low wavelength light is scattered more.
This is called the Tyndall effect. It's commonly seen in skim milk.

If the particle size of the droplets is less than 100 nm (a microemulsion or nanoemulsion), it's
possible for the mixture to be translucent.

Types of emulsions:

The emulsions are of two types:

1.Oil in water o/w type

2.Water in oil w/o type

Test for Identification of Emulsions

The following tests are done to distinguish between o/w and w/o type emulsions.

Test Method Observation Inference

Miscibility/ Emulsion is taken in a beaker The water mixes with o/w type
Dilution test and small volume of water is the emulsion and the
added to it. water remains w/o type
separate.
Dye test Scarlet red (oil soluble) is Droplets are red, o/w type
mixed with the emulsion and background is
a drop of it is placed on a colorless
microscopic slide and Droplets are colorless, w/o type
viewed under microscope. background is red.
Conductivity A pair of electrodes is dipped The bulb glows. Water conducts
test in an emulsion and the electricity, so o/w
electrodes are connected to a w/o
battery, a bulb and a switch.
The switch is put on. The bulb did not glow.
Fluorescence Emulsion taken on The whole field w/o
test microscopic observation fluorescence indicates
under ultraviolet radiation. that oil is present in
continous phase.
Droplets fluorescence
indicates that oil is o/w
present in disperse
phase
Method of preparation of emulsions

The following methods are commonly used for the preparation of emulsions on a small scale:

1. Dry gum method 2. Wet gum method 3. Bottle method 4. Others

For preparing any emulsion with gum acacia first a primary emulsion is produced (w/o type).
Then it is diluted with more volume of water to prepare the final emulsion (o/w type). The
formula is as follows:
Type of oil Example of oil Ratio of oil:water:gum Method used

Fixed oil Castor oil, Almondoil, 4 : 2 : 1 Wet gum, Dry gum

Arachis oil, Cod-liver
oil

Mineral oil Liquid paraffin 3:2:1 Wet gum, Dry gum

Volatile oil Turpentine oil, 2 : 2 : 1 Bottle method

Peppermint oil,
Cinnamon oil

1. Dry gum method

1. The required quantity of oil is measured in a dry container and taken in a mortar.

2. The calculated quantity of the gum acacia (i.e. 1part) is taken in the mortar and triturated to
form a uniform paste.

3.The calculated quantity of water to form primary emulsion (i.e. 2parts) is taken triturated
vigorously till a clicking sound is produced and the product becomes whitish. The emulsion
produced at this stage is called primary emulsion (w/o).

4. Rest of the water (or vehicle) is added in small volume and mixed thoroughly to produce
the final emulsion.

5. The emulsion is transferred to the bottle, capped, polished and labeled.

2. Wet gum method

1. The calculated quantity of the gum acacia (i.e. 1part) is taken in a mortar.

2. The calculated quantity of water is taken in the mortar and triturated to form mucilage.

3. The oil is added in small portions to the mucilage and triturated vigorously until a clicking
sound is produced and the product becomes whitish. The emulsion produced at this stage is
called primary emulsion (w/o).

4. Rest of the water (or vehicle) is added in small volume and mixed thoroughly to produce
the final emulsion.

5. The emulsion is transferred to the bottle, capped, polished and labeled.

3. Bottle method

Bottle method is used for preparation containing volatile oils and low viscosity oils.The
proportion of oil : water : gum = 2 : 2 : 1

1. The required quantity of oil (2 parts) is measured and is transferred into a large bottle.

2. Calculated quantity of powdered acacia (1 part) is taken in the bottle and closed. The bottle
is shaken vigorously until the oil and gum are mixed thoroughly.

3. The calculated amount of water (2 parts) is taken in the bottle and closed. It is shaken
vigorously to form the primary emulsion.

4. Rest of the water is added in small portions and shaken vigorously to mix.

5. The emulsion is transferred to the final bottle, closed, polished and labeled.

4. Other methods

A coarse emulsion is produced which is then passed through hand homogenizer many times
until a uniform emulsion is produced.

Examples of homogenizers are: Hand homogenizer, Silverson mixer homogenizer, Colloid

mill.

These homogenizers are based on the principle that the larger globules in coarse emulsions
are broken down into smaller globules when passed through small orifice (hole) of the
instruments.

Storage: The emulsions should be packed in a bottle leaving space over the preparation for
shaking before use. Should be stored in a cool place. It should not be stored in high
temperature or in refrigerator (it will crack).

Emulsions for internal use: Packed in narrow mouthed plain bottle.

Emulsions for external use: Packed in wide (mouthed if viscous), fluted bottle.

Label: SHAKE WELL BEFORE USE.

Emulsifying Agents

Emulsions are stabilized by adding an emulsifier or emulsifying agents. These agents have
both a hydrophilic and a lipophilic part in their chemical structure. All emulsifying agents
concentrate at and are adsorbed onto the oil:water interface to provide a protective barrier
around the dispersed droplets. In addition to this protective barrier, emulsifiers stabilize the
emulsion by reducing the interfacial tension of the system. Some agents enhance stability by
imparting a charge on the droplet surface thus reducing the physical contact between the
droplets and decreasing the potential for coalescence. Some commonly used emulsifying
agents include tragacanth, sodium lauryl sulfate, sodium dioctyl sulfosuccinate, and polymers
known as the Spans® and Tweens®.
Emulsifying agents can be classified according to: 1) chemical structure; or 2) mechanism of
action. Classes according to chemical structure are synthetic, natural, finely dispersed solids,
and auxiliary agents. Classes according to mechanism of action are monomolecular,
multimolecular, and solid particle films. Regardless of their classification, all emulsifying
agents must be chemically stable in the system, inert and chemically non-reactive with other
emulsion components, and nontoxic and nonirritant. They should also be reasonably odorless
and not cost prohibitive.

Stability of Emulsion

An emulsion is considered to be physically unstable if :

a) The internal phase tends to form aggregates of globules.

b) Large globules or aggregates of globules rise to the top or fall to the bottom of the
emulsion to form a concentrated layer of the internal phase.

c) If all or part of the liquid of the internal phase becomes "unemulsified on the top or bottom
of the emulsion.

Separation of the internal phase from the external phase is called BREAKING of the
emulsion. This is irreversible.

-Protect emulsions against the extremes of cold and heat.

-Emulsions may be adversely affected by microbial contamination.

Instability

Emulsion stability refers to the ability of an emulsion to resist change in its properties over
time. There are four types of instability in emulsions: flocculation, creaming, coalescence and
Ostwald ripening. Flocculation occurs when there is an attractive force between the droplets,
so they form flocs, like bunches of grapes. Coalescence occurs when droplets bump into each
other and combine to form a larger droplet, so the average droplet size increases over time.
Emulsions can also undergo creaming, where the droplets rise to the top of the emulsion
under the influence of buoyancy, or under the influence of the centripetal force induced when
a centrifuge is used.

An appropriate "surface active agent" (or "surfactant") can increase the kinetic stability of an
emulsion so that the size of the droplets does not change significantly with time. It is then
said to be stable.

Monitoring physical stability

The stability of emulsions can be characterized using techniques such as light scattering,
centrifugation and rheology. Each method has advantages and disadvantages.

Accelerating methods for shelf life prediction

The kinetic process of destabilization can be rather long – up to several months, or even years
for some products. Often the formulator must accelerate this process in order to test products
in a reasonable time during product design. Thermal methods are the most commonly used -
these consist of increasing the emulsion temperature to accelerate destabilization (if below
critical temperatures for phase inversion or chemical degradation). Temperature affects not
only the viscosity, but also the interfacial tension in the case of non-ionic surfactants, or on a
broader scope, interactions of forces inside the system. Storing an emulsion at high
temperatures enables the simulation of realistic conditions for a product (e.g. a tube of
sunscreen emulsion in a car in the summer heat), but also to accelerate destabilization
processes up to 200 times.

Mechanical methods of acceleration, including vibration, centrifugation, and agitation, can

also be used.

These methods are almost always empirical, without a sound scientific basis.

Physical instability

i. Flocculation

ii. Creaming or sedimentation

iii. Aggregation or coalescence iv. Phase inversion

Flocculation :

Re dispersible association of particle within an emulsion to form large aggregates. Precursor

to the irreversible coalescence. Differs from coalescence mainly in that interfacial film and
individual droplets remain intact. Influenced by the charges on the surface of the emulsified
globules.

Flocculation is the result of van der Waals attraction that is universal for all disperse systems.
The van der Waals attraction GA was described before. GA is inversely proportional to the
droplet–droplet distance of separation h and it depends on the effective Hamaker constant A
of the emulsion system. One way to overcome the van der Waals attraction is by electrostatic
stabilization using ionic surfactants, which results in the formation of electrical double layers
that introduce a repulsive energy that overcomes the attractive energy. Emulsions stabilized
by electrostatic repulsion become flocculated at intermediate electrolyte concentrations (see
below). The second and most effective method of overcoming flocculation is by ‘‘steric
stabilization’’ using nonionic surfactants or polymers. Stability may be maintained in
electrolyte solutions (as high as 1 mol dm−3 depending on the nature of the electrolyte) and
up to high

temperatures (in excess of 50 ◦C) provided that the stabilizing chains (e.g., PEO) are still in
better than θ-conditions (χ < 0.5).
Creaming or Sedimentation of Emulsions

Creaming is either upward movement or downward movement of dispersed droplets of

emulsion relative to the continuous phase ( due to the density difference between two
phases). Rate of creaming can be calculated using Stoke’s law .

This is the result of gravity, when the density of the droplets and the medium arenot equal.
When the density of the disperse phase is lower than that of the medium,creaming occurs,
whereas if the density of the disperse phase is higher than thatof the medium, sedimentation
occurs. Figure 1.27 gives a schematic picture forcreaming of emulsions for three cases.

Case (a) represents the situation for small droplets (< 0.1 μm, i.e., nanoemulsions)whereby
the Brownian diffusion kT (where k is the Boltzmann constantand T is the absolute
temperature) exceeds the force of gravity (mass ×acceleration due to gravity g)

KT >> 4/3 πR3ρgL

where R is the droplet radius, ρ is the density difference between the droplets and the
medium, and L is the height of the container.

Case (b) represents emulsions consisting of ‘‘monodisperse’’ droplets withradius >1 μm. In
this case, the emulsion separates into two distinct layers withthe droplets forming a cream or
sediment leaving the clear supernatant liquid.This situation is seldom observed in practice.

Case (c) is that for a polydisperse Emulsion Formation, Stability, and Rheology

(practical) emulsions, in which case the droplets will cream or sediment at various

rates. In the last case, a concentration gradient build up with the larger droplets

staying at the top of the cream layer or the bottom of the sediment

Creaming or Sedimentation Rates

1) Very dilute emulsions (φ < 0.01). In this case, the rate could be calculatedusing Stokes’
law that balances the hydrodynamic force with gravity force

Hydrodynamic force = 6πηoRvo

Gravity force = 4/3πR3ρg

vo = 2/9ρgR2ηo

vo is the Stokes’ velocity and ηo is the viscosity of the medium.

For an O/W emulsion with ρ = 0.2 in water (ηo ∼ 10−3 Pa·s), the rate of creaming or
sedimentation is ∼4.4 × 10−5 ms−1 for 10 μm droplets and∼4.4 × 10−7 ms−1 for 1 μm
droplets. This means that in a 0.1m container creaming or sedimentation of the 10 μm
droplets is complete in ∼0.6 h and
for the 1 μm droplets this takes ∼60 h.

2) Moderately concentrated emulsions (0.2 < φ < 0.1). In this case, one has totake into
account the hydrodynamic interaction between the droplets, which reduces the Stokes
velocity to a value v given by the following expression

v = vo(1 − kϕ) (1.76)

where k is a constant that accounts for hydrodynamic interaction. k is of the order of 6.5,
which means that the rate of creaming or sedimentation is reduced by about 65%.

3) Concentrated emulsions (φ >0.2). The rate of creaming or sedimentation becomes a

complex function of φ as is illustrated in Figure 1.28, which also shows the change of relative
viscosity ηr with φ. As can be seen from the above figure, v decreases with increase in φ and
ultimately it approaches zero when φ exceeds a critical value, φp, which is the so-called
‘‘maximum packing fraction.’’ The value of φp for monodisperse ‘‘hard spheres’’ ranges
from 0.64 (for random packing) to 0.74 for hexagonal packing. The value of φp exceeds 0.74
for polydisperse systems. Also for emulsions that are deformable, φp can be much larger than
0.74. The above figure also shows that when φ approaches φp, ηr approaches ∞. In practice,
most emulsions are prepared at φ values well below φp, usually in the range 0.2–0.5, and
under these conditions, creaming or sedimentation is the rule ather than the exception.
Several procedures may be applied to reduce or eliminate.

Prevention of Creaming or Sedimentation

1) Matching density of oil and aqueous phases:Clearly, if ρ = 0, v = 0; However, this method

is seldom practical. Density matching, if possible, only occurs at one temperature.

2) Reduction of droplet size: As the gravity force is proportional to R3, then if R is reduced
by a factor of 10, the gravity force is reduced by 1000. Below a certain droplet size (which
also depends on the density difference between oil and water), the Brownian diffusion may
exceed gravity and creaming or sedimentation is prevented. This is the principle of
formulation of nanoemulsions (with size range 20–200 nm), which may show very little or
no creaming or sedimentation. The same applies for microemulsions (size range 5–50 nm).

3) Use of ‘‘thickeners’’: These are high-molecular-weight polymers, natural, or synthetic

such as Xanthan gum, hydroxyethyl cellulose, alginates, and carragenans. To understand the
role of these ‘‘thickeners,’’ let us consider the gravitational stresses exerted during creaming
or sedimentation

Stress = mass of drop × acceleration of gravity = 4/3πR3ρg

To overcome such stress, one needs a restoring force

Restoring force = area of drop × stress of rop = 4πR2σp

Thus, the stress exerted by the droplet σp is given by

 σp = ρRg3

Simple calculation shows that σp is in the range 10−3 to 10−1 Pa, which implies that for
prediction of creaming or sedimentation one needs to measure the viscosity at such low
stresses. This can be obtained by using constant stress or creep measurements. The above-
described ‘‘thickeners’’ satisfy the criteria for obtaining very high viscosities at low stresses
or shear rates. This can be illustrated from plots of shear stress σ and viscosity η versus shear
rate γ (or shear stress), These systems are described as ‘‘pseudoplastic’’ or shear thinning.
The low shear (residual or zero shear rate) viscosity η(o) can reach several thousand Pascal-
second, and such high values prevent creaming or sedimentation.

The above behavior is obtained above a critical polymer concentration (C*), which can be
located from plots of log η versus log C as shown in Figure 1.30. Below C*, the log η − log C
curve has a slope in the region of 1, whereas above C*, the slope of the line exceeds

3. In most cases, good correlation between the rate of creaming or sedimentation and η(o) is
obtained.

4) Controlled flocculation: As discussed earlier, the total energy distance of separation curve
for electrostatically stabilized shows a shallow minimum (secondary minimum) at relatively
long distance of separation between the droplets. By addition of small amounts of electrolyte,
such minimum can be made sufficiently deep for weak flocculation to occur. The same
applied for sterically stabilized emulsions, which show only one minimum, whose depth can
be controlled by reducing the thickness of the adsorbed layer. This can be obtained by
reducing the molecular weight of the stabilizer and/or addition of a nonsolvent for the chains
(e.g., electrolyte). The above phenomenon of weak flocculation may be applied to reduce
creaming or sedimentation, although in practice this is not easy since one has also to control
the droplet size.

5) Depletion flocculation: This is obtained by addition of ‘‘free’’ (nonadsorbing) polymer in

the continuous phase [32]. At a critical concentration, or volume fraction of free polymer,
φ+p , weak flocculation occurs because the free polymer coils become ‘‘squeezed out’’ from
between the droplets. It shows when the situation when the polymer volume fraction
exceedsthe critical concentration. The osmotic pressure outside the droplets is higher than in
between the droplets, and this results in attraction whose magnitude depends on the
concentration of the free polymer and its molecular weight, as well as the droplet size and φ.
The value of φ+p decreases with increase in the molecular weight of the free polymer. It also
decreases as the volume fraction of the emulsion increases. The above weak flocculation can
be applied to reduce creaming or sedimentation although it suffers from the following
drawbacks: (i) temperature dependence; as the temperature increases, the hydrodynamic
radius of the free polymer decreases (due to dehydration) and hence more polymer will be
required to achieve the same effect at lower temperatures. (ii) If the free polymer
concentration is increased above a certain limit, phase separation may occur and the
flocculated emulsion droplets may cream or sediment faster than in the absence of the free
polymer.
Aggregation (or) coalescence:

Dispersed particles come together but do not fuse. Coalescence : It is the process by which
emulsified particles merge with each to form large particles. Breaking : It is the destroying of
the film surrounding the particles. The major factor to prevent coalescence is increasing the
mechanical strength of the interfacial film.

When two emulsion droplets come in close contact in a floc or creamed layer or during
Brownian diffusion, thinning and disruption of the liquid film may occur resulting in eventual
rupture. On close approach of the droplets, film thickness fluctuations may occur –
alternatively, the liquid surfaces undergo some fluctuations forming surface waves, as
illustrated in Figure 1.35.The surface waves may grow in amplitude and the apices may join
as a result of the strong vander Waals attraction (at the apex, the film thickness is the
smallest). The same applies if the film thins to a small value (critical thickness for
coalescence).

A very useful concept was introduced by Deryaguin and Scherbaker whosuggested that a
‘‘disjoining pressure’’ π(h) is produced in the film that balances the excess normal pressure

π(h) = P(h) − Po (1.92)

where P(h) is the pressure of a film with thickness h and Po is the pressure of a

sufficiently thick film such that the net interaction free energy is zero.

π(h) may be equated to the net force (or energy) per unit area acting across thefilm

π(h) = −dGTdh

where GT is the total interaction energy in the film.

π(h) is made of three contributions due to electrostatic repulsion (πE), steric

repulsion (πs), and van der Waals attraction (πA)

π(h) = πE + πs + πA (1.94)

To produce a stable film πE + πs >πA, this is the driving force for prevention of coalescence
that can be achieved by two mechanisms and their combination:

(i) increased repulsion both electrostatic and steric and

(ii) dampening of thefluctuation by enhancing the Gibbs elasticity. In general,
smaller droplets are lesssusceptible to surface fluctuations and hence
coalescence is reduced. This explains
Several methods may be applied to achieve the above effects:

1) Use of mixed surfactant films: In many cases using mixed surfactants, for example,
anionic and nonionic or long-chain alcohols, can reduce coalescence as a result of several
effects such as igh Gibbs elasticity, high surface viscosity, and hindered diffusion of
surfactant molecules from the film.

2) Formation of lamellar liquid crystalline phases at the O/W interface: This mechanism was
suggested by Friberg and coworkers, who suggested that surfactant or mixed surfactant film
can produce several bilayers that ‘‘wrap’’ the droplets. As a result of these multilayer
structures, the potential drop is shifted to longer distances thus reducing the van der Waals
attraction. For coalescence to occur, these multilayers have to be removed ‘‘two-by-two’’
andthis forms an energy barrier preventing coalescence.

Rate of Coalescence

As film drainage and rupture is a kinetic process, coalescence is also a kinetic process. If one
measures the number of particles n (flocculated or not) at time

tn = nt + nvm

where nt is the number of primary particles remaining and n is the number of aggregates
consisting of m separate particles. For studding emulsion coalescence, one should consider
the rate constant of flocculation and coalescence. If coalescence is the dominant factor, then
the rate K follows a first-order kinetics

n = no /Kt [1 + exp(−Kt)]

which shows that a plot of log n versus t should give a straight line from which K

Phase inversion: An emulsion is said to invert when it changes from an o/w to w/o or vice
versa. It occurs due to : Addition of electrolyte Addition of CaCl2 into o/w emulsion by
sodium soaps can be inverted to w/o.

(i) changing the chemical nature of emulsifier:For instance, an o/w emulsion is prepared
using sodium stearate. Then calcium chloride is added to form calcium stearate,which is oil
soluble. Therefore oil phase becomes the continuous phase and w/o emulsion is produced.
Eg: white linement.

(ii) altering the phase volume ratio: In this method, o/w type of emulsifier is mixed with an
oil and then a small amount of water is added. Since the volume of water is small compared
to the oil. w/o emulsion will be formed. As more water is added slowly, the inversion point is
gradually reached and the water as well as emulsifier envelop the oil to small globules
yielding an o/w emulsion.

If the method is not controlled properly, phase inversion can give a bad emulsion.

Phase inversion of emulsions can be one of two types: transitional inversion induced by
changing the facers that affect the HLB of the system, for example, temperature and/or
electrolyte concentration and catastrophic inversion, which is induced by increasing the
volume fraction of the disperse phase.
Catastrophic inversion is the variation of viscosity and conductivity with the oil volume
fraction φ. As can be seen, inversion occurs at a critical φ, which may be identified with the
maximum packing fraction. At φcr, η suddenly decreases – the inverted W/O emulsion has a
much lower volume fraction. κ also decreases sharply at the inversion point because the
continuous phase is now oil. Earlier theories of phase inversion were based on packing
parameters. When φ exceeds the maximum packing (∼0.64 for random packingand∼0.74 for
hexagonal packing of mono disperse spheres; for poly disperse systems, the maximum
packing exceeds 0.74), inversion occurs. However, these theories are not adequate, because
many emulsions invert at φ values well below the maximum packing as a result of the change
in surfactant characteristics with variation of conditions. For example,

when using a nonionic surfactant based on PEO, the latter chain changes its solvation by
increase of temperature and/or addition of electrolyte. Many emulsions show phase inversion
at a critical temperature (the PIT) that depends on the HLB number of the surfactant as well
as the presence of electrolytes. By increasing temperature and/or addition of electrolyte, the
PEO chains become dehydrated and finally they become more soluble in the oil phase. Under
these conditions, the O/W emulsion will invert to a W/O emulsion. The above dehydration
effect amounts to a decrease in the HLB number and when the latter reaches a value that is
more suitable for W/O emulsion inversion will occur. At present, there is no quantitative
theory that accounts for phase inversion of emulsions.

Factors which improve physical stability

1.particle size:as the globule size reduced, they tend to exhibit Brownian movement.
According to stoke’s law, the diameter of the globule is considered as a major factor in
creaming of a emulsions. In general, the rate of creaming decreases four fold, when the
globule diameter is halved. In microemulsions, the rate of creaming is insignificant. It is
necessary to choose optimum globule size for maximum stability.

2.particle size distribution:In general globules of uniform size impart maximum stability. In
such emulsions, globules pack loosely and globule to globule contact is less.however, it is
difficult to achieve a monodisperse system due to variety of factors such as viscosity, phase
volume ratio, density of phases etc. hence, an optimum degree of size dispersion range should
be chosen to achieve maximum physical stability. If the sizes of globules are not uniform,
globules of smaller size occupies the spaces between the larger globules.this type of closed
packing induces greater cohesion of globules which leads to coalescence.

3.viscosity:As the viscosity increases, flocculation of globules will be reduced because the
mobility of globules is restricted. Simultaneously the Brownian movement of globules will
also be hindered, leading to creaming. Due to this antagonistic effect, an optimum viscosity is
desirable for good stability.

Various thickening agents such as tragacanth, veegum, cellulose derivatives are employed to
formulate emulsions for internal use (o/w type). Long chain fatty acidsand alcohols such as
beeswax, stearic acid, stearyl alcohol etc., are used when oil is the continuous phase. When
oil is the continuous phase in an emulsion viscosity determination is also an important quality
control tool in product evaluation.

4.Phase volume ratio:In an emulsion the relative volume of water and oil is expressed as
phase volume ratio.

Most medicinal emulsions are prepared with a volume ratio of 50:50. This proportion brings
about loose packing of globules.uniform spherical globules in loose packing have a porosity
of 48% of the bulk volume. The remaining volume is occupied by the spherical globules.

The upper limit 74% of oil can be incorporated in an emulsion but it leads to breaking of an
emulsion. This value is referred to as critical point of phase volume ratio.

5.charge of electric double layer: When ionic type of emulsifier is employed, the electrical
double layer posses charge. The repulsive forces due to like charges on the surface of the
globules, prevent the fluctuation of globules

6.physical properties of interface:The interface film of the emulsifier is responsible for the
stability of the p[roduct. The film should be elastic enough to form rapidly as soon as droplets
are produced. This behaviour facilitates the production of emulsions. Similarly on moderate
shaking emulsion dhould be reonstitute.

7.Densities of phases:It is not an usual practice to adjust the density of the phases to the
same value. Oil phase density can be enhanced by adding brominated oil, when oil is an
external phase.

8.Temperature fluctuations:Elevated temperatures alter the partition characteristics of the

emulsifiers and preservatives. The net result is instability. Temperature also enhances the
chemical degradation of drugs and other ingredients. The chemical instability also leads to
physical instability. At high temperatures external phase water may evaporate making the
product more (o/w) concentrated.At lower temperature, the aqueous phase may contain ice
crystals, which rupture the interfacial film and break the emulsion. Care should be taken to
prevent temperature fluctuations during manufacturing and storage

Preservation Of Emulsions:It is necessary to preserve the emulsions

from microorganisms as these can proliferate easily in emulsified systems with
high water content, particularly if carbohydrates, proteinsor steroidal materials are also
present.

Preservation from microorganisms: It is necessary to preserve the emulsions

from microorganisms as these can proliferate easily in emulsified systems with
high water content, particularly if carbohydrates, proteins or steroidal materials are also
present.

Contamination due to microorganisms can result in problems such as color and odor
change, gas production, hydrolysis, pH change and eventually breaking of emulsion.
Therefore is necessary that emulsified systems be adequately preserved. An
ideal preservative should be nonirritant, nonsensitizing and nontoxic in the concentration
used. It should be physically as well as chemically compatible with other ingredients of the
emulsions and with the proposed container of the product. It should not impart any taste,
color or odor to the product. It should be stable and effective over a wide range of pH and
temperature. It should have have a wide spectrum of activity against a range of bacteria,
yeasts and moulds. The selective preservative should have high water solubility and a low
oil/water partition coefficient. It should have bactericidal rather than bacteriostaticactivity.

Examples of antimicrobial preservatives used to preserve emulsified systems include

parahydroxybenzoate esters such as methyl, propyl and butyl parabens, organic acids such
as ascorbic acid and benzoic acid, organic mercurials such as phenylmercuric acetate and
phenylmercuric nitrate, quarternary ammonium compounds such as cetrimide, cresol
derivatives such as chlorocresol and miscellaneous agents such as sodium benzoate,
chloroform and phenoxyethanol.

Microbial contamination may occur due to: Usage of impure raw materials Poor sanitation
conditions Invasion by an opportunistic microorganisms.

Contamination by the consumer during use of the product.. Precautions to prevent microbial
growth Use of uncontaminated raw materials Careful cleaning of equipment with live stream
. Addition of Preservative agent.

Some of the factors to be considered for the selection of preservatives are:

➢ Type of emulsion(o/w or w/o)

➢ Volume fraction of aqueous phase
➢ pHof the a aqueous phase
➢ binding of ingredients in the formulation
➢ nutritive value
➢ degree of aeration
➢ type of container
Preservation from oxidation:Oxidative changes such as rancidity and spoilage due to
atmospheric oxygen and effects of enzymes produced by micro-organisms is seen in many
emulsions containing vegetables and mineral oils and animal fats. Antioxidants can be used
to prevent the changes occurring due to atmospheric oxygen. Antioxidants are agents having
a high affinity for oxygen and compete for it with labile substances in the formulation. The
ideal antioxidant should be nontoxic, nonirritant, effective at low concentration under the
expected conditions of storage and use, soluble in the medium and stable. Antioxidants for
use in oral preparation should also be odorless and tasteless.

Some of the commonly used antixidants for emulsified systems include alkyl gallate
such as ethyl, propyl or dodecyl gallate, butylated sshydroxyanisole (BHT), butylated
hydroxytoluene (BHT)
 UNIT 4: SUPPOSITORIES: PHARMACEUTICAL INCOMPATIBILITIES:

SUPPOSITORIES

Definition: Suppositories are specially shaped Semi solid dosage form of medicament for
insertion into body cavities other than mouth.They may be inserted into rectum, vagina or the
urethra. This products are so formulated that after insertion, they will either melt or dissolve
in the cavity fluids to release the medicament.

Types of suppositories:There are five types’ suppositories as follows:

1. Rectal suppositories:These are meant for introduction into the rectum for their systemic
effect. They are tapered at one or both ends and usually weigh about 2 gm. The rectal
suppositories meant for children are smaller in size and weight is 1 gm.

Advantages of rectal suppositories

(i)Mechanical action: The rectal suppositories are extensively used as a mechanical aid
to bowel evacuation which produce its action by either irritating the mucous membrane of the
rectum (e.g. glycerol and bisacodyl) or by lubricating action or by mechanical lubrication.

(ii)Local action: The rectal suppositories may be used for Soothing, Antiseptic, Local
Anaesthetic action or for Astringent effect. Therefore, they may contain

Soothing e.g. zinc oxide

Local anaesthetic- e.g. cinchocaine, benzocaine

Astringents e.g. bismuth subgallate, hamamelis extract and tannic acid

Antiinflammatory e.g. hydrocortisone and its acetate.

(iii) To provide systemic action: Suppositories are convenient mode of administration of

drugs which irritate the gastrointestinal tract, cause vomiting, are destroyed by the hepatic
circulation or are destroyed in the stomach by pH changes, enzymes etc.

Partial bypass: The lower portion of the rectum affords a large absorption surface area from
which the soluble substances can absorb and reach the systemic circulation.

e.g. Aminophylline-used in asthmatic and chronic bronchitis.

Morphine-a powerful analgesic

Ergotamine tartarate-used to treat migraine

Indomethacin and phenyl butazone- analgesic and anti-inflammatory

actions.

Systemic treatment by the rectal route is of particular value for-

 (a) Treating patients who are unconscious, mentally disturbed or unable to tolerate oral
medication because of vomiting or pathological conditions of the alimentary tract.

(b) Administering drugs, such as aminophylline, that cause gastric irritation and

(c) Treating infants.

2. Vaginal suppositories: They are meant for introduction into vagina. They are larger than
rectal suppositories and vary in weight from 3 to 6 gm or more. They may be conical, rod-
shaped or wedge shaped. They are exclusively used for their local action on vagina.

3. Urethral Suppositories: They are meant for introduction into the urethra. Their weight
varies from 2 to 4 gm and length from 2 to 5 inch. Urethral suppositories are very rarely used.

4. Nasal suppositories: They are meant for introduction into nasal cavity. They are similar in
shape to urethral suppositories. Their weight is about 1 gm and length 9-10 cm. They are
always prepared with glycero-gelatin base.

5. Ear cones: They are meant for introduction into the ear. Generally theobroma oil is used
as a base. They are prepared in a urethral suppositories mould and cut according to the
required size.

Ideal Properties of a Suppositories Base

1. It should melt at body temperature or dissolve or disperse in body fluids.

2. It should release any medicament readily.

3. It should keep its shape when being handled.

4. It should be non-toxic and non-irritant to the mucous membrane.

5. It should be stable on storage.

6. It should be compatible with any added medicament.

7. It should be stable if heated above its melting point.

8. It should be easily moulded and should not adhere to the mould.

9. It should be easily mouldable by pouring or cold compression.

10.It should shrink so that it comes out easily from the mould without the use of any lubricants.

For fatty bases the following additional specifications are required:

11. “Acid value” is below 0.2

12. “Saponification value” ranges from 200 to 245

13. “Iodine value” is less than 7

14. The interval point and solidification point is small.

[Since it is not possible to get all the above mentioned qualities in a single base, so a
combination of bases is used to get a product of required qualities. A number of patent
“improved” suppository bases are available. Most of these are mixtures of fats, waxes and
esters in specific proportions according to the desired qualities of the product to be obtained.
Glycerogelatin and polyethylene glycols are being widely used as suppository bases, though
theobroma oil is extensively used in extemporaneous preparations but it is losing its
importance because it is unstable to heat and has undesirable physical properties.]

TYPES OF SUPPOSITORY BASES

Suppository bases fall into two classes as follows:

1. Fatty bases - these melt at body temperature.

2. Water-soluble or water miscible bases - these dissolve or disperse in rectal secretions.

3. Emulsifying bases

1.FATTY BASES

Theobroma oil (Cocoa butter)

It is a yellowish-white solid with a chocolate-like odour.

It is a mixture of glyceryl esters of stearic, palmitic, oleic and other fatty acids.

Advantages:

(a)A melting point range of 30 to 36 0C; hence it is solid at normal room temperatures but
melts in the body.

(b)Ready liquefaction on warming and rapid setting on cooling.

(c)Miscibility with many ingredients.

(d)Blandness i.e. does not produce irritation.

Disadvantages:

(a) Polymorphism

When melted and cooled it solidifies in different crystalline forms, depending on the
temperature of melting, rate of cooling and size of the mass. If melted at not more than 360C
and slowly cooled it forms stable beta crystals with normal melting point, but if over-heated it
may produce, on cooling, unstable gamma crystals. These unstable forms eventually return to
the stable condition but this may take several days and mean while, the suppositories may not
set at room temperature or if set by cooling, may re-melt in the warmth of the patient’s home.

(b) Adherence to mould

Because theobroma oil doesn’t contract enough on cooling to loosen the suppositories in the
mould, sticking may occur, particularly if the mould is warm. This is prevented by lubricating
the mould before use.

(c) Softening point too low for hot climates

To raise the softening point, white beeswax may be added to theobroma oil suppositories
intended for use in tropical and subtropical countries.

(d) Melting point reduced by soluble ingredients

Substances, such as chloral hydrate, that dissolve in theobroma oil, may lower its melting
point to such an extent that the suppositories are too soft for use. To restore the melting point,
a controlled amount of white beeswax may be added.

(e) Slow deterioration during storage

This is due to oxidation of the unsaturated glycerides.

(f) Poor water absorbing capacity

This fault can be improved by the addition of emulsifying agents.

(g) Leakage from the body

Sometimes melted base escapes from the rectum or vagina. This is most troublesome with
suppositories because of their larger size and therefore, these are rarely made with theobroma
oil.

(h) Relatively high cost

Synthetic fats

As a substitute of theobroma oil a number of hydrogenated oils, e.g. hydrogenated edible oil,
arachis oil, coconut oil, palm kernel oil, stearic and a mixture of oleic and stearic acids are
recommended.

Advantages of these synthetic fats over theobroma oil:

1.Their solidifying points are unaffected by overheating.

2.They have good resistance to oxidation because their unsaturated fatty acids have been
reduced.

3. Their emulsifying and water absorbing capacities are good

4. No mould lubricant is required because they contract significantly on cooling.

5.They produce colorless, odourless and elegant suppositories.

Disadvantages:

1.They should not be cooled in refrigerator because they become brittle if cooled
quickly. Certain additives e.g. 0.05 % polysorbate80, help to correct this fault.

2.They are more fluid than theobroma oil when melted and at this stage sedimentation rate is
greater. Thickeners such as magnesium stearate , bentonite and colloidal silicon dioxide, may
be added to reduce this.

2.WATER SOLUBLE AND WATER MISCIBLE BASES

Glycero-Gelatin base

● This is a mixture of glycerol and water made into a stiff jelly by adding gelatin.

●It is used for the preparation of jellies, suppositories and pessaries. The stiffness of the mass
depends upon the proportion of gelatin used which is adjusted according to its use.

●The base being hydrophilic in nature, slowly dissolves in the aqueous secretions and
provide a slow continuous release of medicament. Glycerogelatin base is well suited for
suppositories containing belladonna extract, boric acid, chloral hydrate, bromides, iodides,
iodoform, opium, etc.

●Depending upon the compatibility of the drugs used a suitable type of gelatin is selected for
the purpose. Two types of gelatins are used as suppository base

(i)Type-A or Pharmagel-A which is made by acid hydrolysis (has isoelectric point between 7
to 9 and on the acid side of the range behaves as a cationic agent, being most effective at pH
7 to 8. ) is used for acidic drugs.

(ii)Type-B or Pharmagel-B which is prepared by alkaline hydrolysis (having an isoelectric

point between 4.7 to 5 and on the alkaline side of the range behaves as an anionic agent,
being most effective at pH 7 to 8 ) is used for alkaline drugs

Disadvantages

Glycerogelain base suppositories are less commonly used than the fatty base suppositories
because:

(i)Glycerol has laxative action.

(ii)They are more difficult to prepare and handle.

(iii) Their solution time depends on the content and quality of the gelatin and the age of the
base.

(iv)They are hygroscope, hence must be carefully stored.

(v)Gelatin is incompatible with drugs those precipitate with the protein e.g. tannic acid, ferric
chloride, gallic acid, etc.
Soap-Glycerin Suppositories

●In this case gelatin and curd soap or sodium stearate which makes the glycerin sufficiently
hard for suppositories and a large quantity of glycerin upto 95% of the mass can be
incorporated.

●Further the soap helps in the evacuation of glycerin.

●The soap glycerin suppositories have the disadvantage that they are very hygroscopic,
therefore they must be protected from atmosphere and wrapped in waxed paper or tin foil.

Polyethylene glycol bases / Macrogol bases (Carbowaxes)

Depending on their molecular weight they are available in different physical forms.

I II III IV

Macrogol 400 - - 20 -

Macrogol 1000 - - - 75

Macrogol 1540 - 33 33 -

Macrogol 4000 33 - - 25

Macrogol 6000 47 47 47 -

Water 20 20 - -

By choosing a suitable combination a suppository base with the desired characteristics can be
prepared.

Advantages

1. The mixtures generally have a melting point above 420C, hence, does not require cool
storage and they are satisfactory for use in hot climate.

2. Because of the high melting point they do not melt in the body cavity, rather they gradually
dissolve and disperse, releasing the drug slowly.

3.They do not stick to the wall of the mould since they contract significantly on cooling.

3.EMULSIFYING BASES

These are synthetic bases and a number of proprietary bases of very good quality are
available, few of which are described below:

Witepsol

They consist of triglycerides of saturated vegetable acids (chain length C12 to C18) with
varying proportions of partial esters.
Massa Esterium

This is another range of bases, consisting of a mixture of di-, tri- and mono- glycerides of
saturated fatty acids with chain lengths of C11 to C17.

Massuppol

It consists of glyceryl esters mainly of lauric acid, to which a small amount of glyceryl
monostearate has been added to improve its water absorbing capacity.

Advantages of these bases over cocoa butter:

1.Over heating does not alter the physical characteristics.

2.They do not stick to the mould. They do not require previous lubrication of the mould

3.They solidify rapidly.

4.They are less liable to get rancid.

5.They can absorb fairly large amount of aqueous liquids.

PREPARATION OF SUPPOSITORIES

Suppositories are prepared by two processes: moulding (hot process or fusion process)
and cold compression.

Mould

Various types and sizes of suppository moulds are available. In the dispensary suppository
moulds with six or twelve cavities with desired shape and size may be used. For large scale
production moulds up to 500 cavities may be used.

Moulds are made up of stainless steel, nickel-copper alloy, brass, aluminium or plastic.

For cleaning, lubrication and removal of suppositories the mould can be opened
longitudinally by removing the screw in the centre of the plates.

The nominal capacities of the common moulds are 1g, 2g, 4g and 8g.

Calibration of the mould

The nominal capacity of a mould is not always correct. It will vary for different bases. Each
mould should be calibrated before use by preparing a set of suppositories using
the base alone, weighing the products and taking the mean weight as the true capacity. This is
repeated for each base and the value is recorded for future use.
Lubrication of Moulds

► If the cavities of the mould are imperfect, i.e. poorly polished or scratched, it may be
difficult to remove the cocoa butter suppositories without damaging their surfaces unless a
lubricant is used. In this case an aqueous lubricant is used.

►Glecero-gelatin base is sticky in nature hence they are lubricated with an oily lubricant
e.g. liquid paraffin or arachis oil.

►It is unnecessary to lubricate the mould when synthetic fat or macrogol bases are used. The
products have better surface if the mould is dry.

For theobroma oil the following lubricating preparation is found to be useful:

Soft Soap 10 g

Glycerol 10 ml

Alcohol (90 %) 50 ml

The lubricant should be applied on a pad of gauze or muslin or with a small fairly stiff brush.

To avoid excess lubrication the moulds are closed and kept inverted on a clean tile to drain
out excess lubricant.

Displacement value

The volume of a suppository from a particular mould is uniform but its weight will vary
because the densities of medicaments usually differ from the density of the base with which
the mould was calibrated.

To prepare products accurately, allowance must be made for the change in density of the
mass due to added medicaments. For this purpose the displacement value of a medicament is
taken into consideration.

Definition: The number of parts of medicament (drug) that displaces one part by weight of
the base is known as the displacement value of that drug.

The following table 1 lists the displacement values, with reference to theobroma oil, for
substances prescribed in suppositories.
 Table 1 Drugs and their respective Displacement Value

Drug Displacement Value

Aminophylline 1.5
Bismuth subgallate 3.0
Castor oil 1.0
Chloral hydrate 1.5
Cinchocaine Hydrochloride 1.5
Cocaine hydrochloride 1.5
Hydrocortisone 1.5
Hydrocortisone acetate 1.5
Ichthammol 1.0
Morphine Hydrochloride 1.5
Phenobarbitone 1.0
Resorcinol 1.0
Tannic acid 1.0
Zinc oxide 5.0
Aspirin 1.1
Belladonna Extract 1.2
Bismuth Subgallate 3.0
Bismuth Subnitrate 6.0
Boric Acid 1.5
Codeine Phosphate 1.1
Digitalis Leaf 1.6
Dimenhydrinate 1.3
Diphenhydramine HCl 1.3
Gallic Acid 2.0
Hamamelis Dry Extract 1.5
Quinidine HCl 3.0
Hydrocortisone Acetate 1.5
Menthol 0.7
Morphine Hydrochloride 1.5
Peru Balsam 1.0
Phenobarbital Sodium 1.2
Potassium Bromide 2.2
Quinidine HCl 3.0
Salicylic Acid 1.3
Secobarbital Sodium 1.2
Zinc Sulfate 2.8
Example 1:

If a prescription requires 400 mg of bismuth subgallate per suppository weighing two grams,
what would be the displacement value if it is known that six suppositories with required
bismuth subgallate weigh 13.6 g

Theoretical weight of six cocoa butter suppositories without bismuth subgallate = 12 g

Given weight of six cocoa butter suppositories with bismuth subgallate =13.6 g

Amount of bismuth subgallate in the suppositories = 0.4 × 6 = 2.4 g

Amount of cocoa butter in the bismuth subgallate suppositories = 13.6 − 2.4 = 11.2 g

Cocoa butter displaced by 2.4 g of bismuth subgallate = 12 − 11.2 = 0.8

The displacement value of bismuth subgallate is 2.4/0.8 = X/1, or X=3

Example 2:

If 12 cocoa butter suppositories containing 40% zinc oxide weigh 17.6 grams, what is the
displacement value of zinc oxide? Assume that the suppositories are made in a 1-g mold.

Given weight of 12 suppositories with zinc oxide = 17.6 grams

Weight of zinc oxide in the suppositories = (40/100) × 17.6 = 7.04 g

Weight of cocoa butter in the suppositories = (60/100) × 17.6 = 10.56 g

Theoretical weight of 12 suppositories without zinc oxide = 12 g

Cocoa butter displaced by 7.04 g of zinc oxide = 12 − 10.56 = 1.44

Displacement value of zinc oxide = (7.04/1.44) = (X/1); X = 4.89

Example 3:

From the information provided below, find the displacement value of phenobarbital

sodium: Six phenobarbital sodium suppositories, each containing 60-mg of drug,

weigh 12 g.

The mold of suppository used was 2 g.

Given weight of six suppositories with phenobarbital sodium = 12 g

Weight of phenobarbital sodium = 60 mg × 6 = 360 mg or 0.36 g

Weight of cocoa butter in the suppositories = 12 − 0.36 = 11.64 = 0.36 g

Theoretical weight of six suppositories without phenobarbital sodium = 12 g

Cocoa butter displaced by 0.36 g of phenobarbital sodium = 12 − 11.64 = 0.36 g

Displacement value of phenobarbital sodium = (0.36/0.36) = (X/1); X = 1

METHODS OF PREPARATION

Suppositories can be prepared by one of three methods as follows:

1. Hand Rolling Method:Hand Rolling is the oldest and simplest method of suppository
preparation and may be used when only a few suppositories are to be prepared in a cocoa
butter base. It has the advantage of avoiding the necessity of heating the cocoa butter. A
plastic-like mass is prepared by triturating grated cocoa butter and active ingredients in a
mortar. The mass is formed into a ball in the palm of the hands, then rolled into a uniform
cylinder with a large spatula or small flat board on a pill tile. The cylinder is then cut into the
appropriate number of pieces which are rolled on one end to produce a conical shape.

Effective hand rolling requires considerable practice and skill. The suppository "pipe" or
cylinder tends to crack or hollow in the center, especially when the mass is insufficiently mix
and softened.

2. Compression Molding Method:Compression Molding is a method of preparing

suppositories from a mixed mass of grated suppository base and medicaments which is forced
into a special compression mold. The method requires that the capacity of the molds first be
determined by compressing a small amount of the base into the dies and weighing the
finished suppositories. When active ingredients are added, it is necessary to omit a portion of
the suppository base, based on the density factors of the active ingredients.

3. Fusion Molding Method:Fusion Molding involves first melting the suppository base and
then dispersing or dissolving the drug in the melted base. The mixture is removed from the
heat and poured into a suppository mold. When the mixture has congealed, the suppositories
are removed from the mold. The fusion method can be used with all types of suppositories
and must be used with most of them.

Suppositories are generally made from solid ingredients and drugs which are measured by
weight. When they are mixed, melted and poured into suppository mold cavities, they occupy
a volume – the volume of the mold cavity. Since the components are measured by weight but
compounded by volume, density calculations and mold calibrations are required to provide
accurate doses.

When a drug is placed in a suppository base, it will displace an amount of base as a function
of its density. If the drug has the same density as the base, it will displace an equivalent
weight of the base. If the density of the drug is greater than that of the base, it will displace a
proportionally smaller weight of the base. Density factors for common drugs in cocoa butter
are available in standard reference texts. The density factor is used to determine how much of
a base will be displaced by a drug.
EVALUATION TESTS FOR SUPPOSITORIES

►Test of appearance

►Test of physical strength

►Test of dissolution rate

►Test of melting range

►Test of softening time

►Test of uniformity of drug content

►Test of drug uptake

Test of appearance

All the suppositories should be uniform in size and shape. They should have elegant
appearance. Individual suppositories should be examined for cracks and pits due to
entrapment of air in the molten mass.

Test of physical strength

In this test, tensile strength of suppositories is measured to assess their ability to withstand the
rigors of normal handling.

The apparatus used is called as breaking test apparatus. It consists of a double-wall chamber.
Through the walls of the chamber, water is pumped. The inner chamber consists of a disc
which holds the suppositories. To this disc, a rod is attached. The other end of the rod
consists of another disc on which weights are placed.

Procedure: On the first disc the test suppository is placed. On the second disc a 600 g weight
is placed. At 1 minute interval, 200 g weights are added till the suppository crumbles. All the
weights used are added which gives the tensile strength. Likewise, few more suppositories
are tested and the average tensile strength is calculated. Tensile strength indicates the
maximum force which the suppository can withstand during production, packing and
handling. Large tensile strength indicates fewer tendencies to fracture.

Test of dissolution rate

It is the amount of dosage form that gets dissolved in body fluid in unit time. It is a measure
of the rate of drug release from the suppository.

Two types of apparatus are available for testing the dissolution rate. They are:

(a) Suppository dialysis cell - Lipophilic suppositories are tested using suppository dialysis
cell, which is also called as modified flow-through cell.
(b) Stationary basket - Rotating paddle apparatus ( USP dissolution test apparatus ).
Hydrophilic suppositories are tested using stationary basket - rotating paddle apparatus.

Test of melting range

Both macromelting range and micromelting range are determined.

(a) Macromelting range

It is a measure of the thermal stability of the suppository.

It is the time taken by the entire suppository to melt in a constant temperature water bath. The
test is conducted using the tablet disintegration apparatus.

The suppository is immersed in a constant water bath. Finally the melting range is recorded.

(b) Micromelting range

The melting range of the fatty base is measured in capillary tubes.

Test of softening time

Softening time is the time for which the suppository melts completely at a definite
temperature. This test measures the softening time of suppositories which indicates the
hardness of the base.

Method:The apparatus consists of a cellophane tube tied at the two ends of a condenser. The
two ends of the cellophane tube are open. Water is circulated through the condenser at a
definite rate. As a result, after some time the upper half of the tube opens wide and the lower
half collapses.A suppository is dropped into the water in the condenser. The time period in
which the suppository melts completely is noted as the softening time.

Test of uniformity of drug content

This test is to assess the uniformity of the mixed suppository mass. Different suppositories
are assayed for the drug. All the suppositories should contain the same labelled quantity of
the drug.

Test of drug uptake

Both in-vitro and in-vivo tests should be conducted to assess the amount of drug absorbed
into the systemic circulation.

(a) In-Vitro test

The test conditions should be similar to those inside the human body.

The dissolution apparatus is used which consists of simulated gastric and simulated intestinal
fluids.

Definite number of suppositories are placed in the apparatus.

Aliquot portions of the dissolution medium are withdrawn at definite intervals of time and
drug uptake is measured using a U.V. spectrophotometer.

(b) In-Vivo test

This test is carried in animals or human volunteers.

The suppository is placed in the intended body cavity.

At regular intervals of time, blood samples are collected and the amount of drug present is
determined.

PACKAGING AND STORAGE

Glycerin suppositories and glycerinated gelatin suppositories are packaged in tightly

closed glass containers to prevent a change in moisture content. Suppositories prepared from
a cocoa butter base are usually individually wrapped or otherwise separated in
compartmented boxes to prevent contact and adhesion. Suppositories containing light-
sensitive drugs are individually wrapped in an opaque material such as a metallic foil. In fact,
most commercial suppositories are individually wrapped in either foil or plastic. Some are
packaged in a continuous strip, separated by tearing along perforations. Suppositories are also
commonly packaged in slide boxes or in plastic boxes.
Because suppositories are adversely affected by heat, it is necessary to maintain them in
a cool place. Cocoa butter suppositories must be stored below 30°C (86°F) and preferably in
a refrigerator (2°C to 8°C, or 36°F to 46°F). Glycerinated gelatin suppositories can be stored
at controlled room temperature (20°C to 25°C, or 68°F to 77°F). Suppositories made from a
base of polyethylene glycol may be stored at usual room temperatures.
Suppositories stored in high humidity may absorb moisture and tend to become spongy,
whereas suppositories stored in places of extreme dryness may lose moisture and become
brittle.
PHARMACEUTICAL INCOMPATIBILITIES

INCOMPATIBILITY

Definition: When two or more ingredients of a prescription are mixed together the undesired
change that may take place in the physical, chemical or therapeutic properties of the
medicament is termed as incompatibility.

Importance of Determining Incompatibility: Incompatible products may effect:

■ Safety of medicament.
■Efficacy of product.
■Appearance of a medicine.
■Purpose of medication.

►The most important step in dealing with incompatibility is recognizing by noting an

incompatibility before a prescription is filled.
►The pharmacist can take corrective measures that save both time and material. ►It is easier
to prevent an incompatibility rather than to correct it.
►An incompatibility is not recognized until after the prescription has been compounded.
►The prescription should not be dispensed until the incompatibility has been corrected.
CLASSIFICATION OF INCOMPATIBILITY

Incompatibilities are of three types as follows:

1. Therapeutic incompatibility

2. Physical incompatibility

3. Chemical incompatibility

1. THERAPEUTIC INCOMPATIBILITY

►Usually this incompatibility arises when one or more drugs produces response or intensity
different from that intended in the patients.

Classification

A) Over doses

B) Under doses

C) Improper consumption by the patient

D) Contra-indicated drugs

A) Over doses: This can be sub grouped as follows:

Excessive single dose

►Sometimes a single dose may become overdose depending on the health of the patient e.g.
a normal dose (taking body weight as 70 kg for an adult male) may be overdose for a lowly
built person.

►However it should not be more than 2 to 3 normal dose.

Remedy: The pharmacist should consult the physician and clarify the dose.

Exmple 1

Rx

Atropine sulphate 6 mg

Phenobarbital 360 mg

Make capsules.

Label: One capsule to be taken three times a day before meals.

Comments: In this prescription the doses of both atropine sulphate and phenobarbital are 12
times the normal doses. The physician intended for 12 capsules to be dispensed but he has
mistaken or may be it is an incomplete prescription. Hence, before dispensing the pharmacist
should consult the physician again.

Correct prescription

Rx

Atropine sulphate 6 mg

Phenobarbital 360 mg

Make capsules. Supply 12 capsules.

Label: One capsule to be taken three times a day before meals.

Example 2

Rx

Strychnine sulphate 20 mg

Iron and ammonium citrate 500 mg

Prepare capsules. Supply 12 capsules.

Label: One capsule to be taken three times a day after meals.

Comment: 10 times overdose of strychnine hydrochloride than that of normal. The pharmacist
should consult the physician and obtain the permission to change the dose.

Corrected prescription

Strychnine sulphate 2 mg

Iron and ammonium citrate 500 mg

Prepare capsules. Supply 12 capsules.

Label: One capsule to be taken three times a day after meals.

Excessive daily dose

In this case the daily dose of drug is exceeded.

Exmple 1

Rx

Codeine phosphate 15 mg

Ammonium chloride 500 mg

Prepare capsules and supply 24 capsules.

Label: Two capsules to be taken every hour for cough.

Comment: The U.S.P. recommends that the prescribed dose should be taken after every four
hours and not every hour. Hence the physician should be consulted.

Additive and synergistic combinations:

►There are certain drugs possessing similar pharmacological activity.

►If these drugs are combined together, they may produce additive or synergistic action.

►In such case advice of the physician is necessary.

e.g.

Rx

Amphetamine sulphate 20 mg

Ephedrine sulphate 50 mg

Syrup q.s. 100 ml

Let a mixture be made

Label: Take 25 ml every four hours.

Comment: Both of the drugs are sympathetic stimulants and they are prescribed in their full
dose. The formulation will produce additive overdose effect. Hence, the dose of individual
drug should be reduced.

(B) Under dose: In this type of incompatibility, effect of one drug is reduced or antagonized
by the presence of another drug. This can be exemplified by combination of following types
of drugs:

1.Stimulants like nux-vomica, strychnine sulphate, caffeine etc. with sedatives like
barbiturates, paraldehyde etc.

2.Sympathomimetic or adrenergic like ephedrine, nor-adrenaline with sympatholytic drugs

like ergotamine.

3.Sympathetic stimulants like methamphetamine with parasympathetic stimulants like

pilocarpine.

4.Purgatives like castor oil, liquid paraffin etc with antidiarrheal agents like bismuth
carbonates.

5. Acidifiers like dilute hydrochloric acid and alkalisers like sodium bicarbonate, magnesium
carbonate.

Exmple.

Rx

Aspirin 300 mg

Probenecid 500 mg

Prepare capsules.

Label: One capsule a day for gout.

Aspirin is an NSAID given to reduce the pain and swelling in case of gout attack. Probenecid
blocks the active reabsorption of uric acid from the lumen of nephron, but salicylates
(aspirin) blocks this action of probenecid. Hence, both of the drugs are antagonistic to each
other, so its combination is therapeutically useless.

(C) Improper consumption by the patient:

►In certain prescription some special directions should be written.

►If the patients are nor advised the drugs may not produce the desired action due to low
bioavailability.
Exmple

Rx

Tetracycline hydrochloride 250 mg

Prepare capsules. Supply 10 capsules.

Label: Take one capsule every six hourly.

Comments: Calcium present in milk inactivates the tetracycline, hence a patient may not get
any therapeutic effect if he/she takes the capsule with milk.

Remedy: The pharmacist should advise the patient to take the capsule with water and not with
milk. The patient should not take antacid containing calcium salts.

(D) Contra-indicated drugs

Certain drugs should not be given in particular disease condition

Example:

(i) Corticosteroids are contraindicated in patients with peptic ulcer.

(ii) Vasoconstrictors are contraindicated in hypertensive patients

(iii)Some drugs should not be given in asthmatic patients e.g. barbiturates, morphine etc.

(iv)If a person is allergic to a drug (e.g. penicillin injection) then it should not be given to the
patient.

(v) Certain combination of drugs are contraindicate:

Exmple

Rx

Sulphadiazine 0.25 g

Sulphamerazine 0.25 g

Ammonium chloride 0.50 g

Prepare capsules

Label: Take two capsules six hourly for cough.

Comment: In this prescription ammonium chloride is a urinary acidifier and it could cause
deposition of sulphonamide crystals in the kidney.
2. PHYSICAL INCOMPATIBILITY

►Usually, this is due to immiscibility or insolubility.

►It can cause unsightly, non-uniform products from which removal of an accurate dose is
very difficult.

Classification:

(A) Immiscibility

(B) Insolubility

(C)Liquefaction

(A) Immiscibility

1)Oils are immiscible with water and hence combination of oily drugs with water produces a
product possessing two separate layers.

Remedy: Emulsification or Solubilization can overcome by this problem.

2)Care must be taken when concentrated hydro alcoholic solutions of volatile oils such as
spirits and concentrated waters are used as adjuncts (e.g. as flavouring agents) in aqueous
preparations. Large globules of oils may be separated.

Remedy:To prevent the formation of large globules, the hydro alcoholic solution should
either be gradually diluted with the vehicle before admixture with the remaining ingredients
or poured into the vehicle with constant stirring.

3)Addition of high concentrations of electrolytes to mixture in which the vehicle is a

saturated aqueous solution of a volatile oil causes the oil to separate and collect as a surface
layer.

Example: This happens in Potassium Citrate Mixture B.P.C. in which large quantity of
soluble solids salts out the lemon oil.

Remedy: To disperse the droplets evenly, quillaia tincture is added as a wetting agent.

(B) Insolubility

1)Liquid preparations containing indiffusible solids such as chalk, aromatic chalk powder,
succinyl sulfathiazole and sulphadimidine (in mixtures) and calamine and zinc oxide (in
lotions) - a thickening agent is necessary to obtain a uniform product from which uniform
doses can be removed.

2) Some insoluble powders such as sulphur and certain corticosteroids (hydrocortisone

acetate) and antibiotics are difficult to wet with water.

Remedy: Wetting agents

Example: saponins for sulphur containing lotions and polysorbates in parenteral suspensions
of corticosteroids and antibiotics are used to distribute the powder and prevent formation of a
slowly dispersing, solid stabilised foam on shaking.

3)When a resinous tincture is added to water the water insoluble resin agglomerate forming
indiffusible clots.

Remedy: This is prevented by slowly adding the undiluted dispersion of protective colloid
(Tragacanth mucilage).

Example: Lobelia & Stramonium tincture which should be mixed with tragacanth mucilage
and stirred constantly. This will produce a stable preparation.

4) High concentrations of electrolytes cause cracking of soap emulsions (ionic) by salting out
the emulsifiers.

C) Liquefaction

When certain low melting point solids are powdered together a liquid or soft mass is
produced due to lowering of the melting point of the mixture to below room temperature.
Thus a eutectic mixture is formed.

Any two of the following exhibits this type of behaviour, camphor, menthol, phenol, thymol
and chloral hydrate also sodium salicylate with phenazone.

Example:

Rx

Thymol 250 mg

Camphor 2 mg

Menthol 2 mg

Make powder.

Comments: If these ingredients are triturated together, they will form an eutectic mixture.

Method-I:

All the ingredients are triturated.

An eutectic mixture (liquid) will be formed. The liquid is triturated with enough absorbent
powder e.g. light kaolin or light magnesium carbonate to give a free flowing powder.

Method-II:

Each ingredient is triturated separately with small amount of adsorbent or diluent and then
these powders are lightly mixed by tumbling action) and packed.
The diluent largely prevents contact between the ingredients and adsorbs any liquid that may
be produced.

Example:

Rx

Chloral hydrate 250 mg

Prepare capsules. Supply 10 capsules.

Label: Take the capsules at night time.

Comment: Chloral hydrate is hygroscopic in nature. It will absorb moisture and soften the
hard gelatin capsule shells and the shape of the capsule may change physically.

Remedy: An equal quantity of light magneisum oxide should be mixed with chloral hydrate.

Other adsorbents those may be used are kaolin, talc, starch etc.

Example:

Rx

Aminopyrine 0.3 g

Acetyl salicylic acid 0.2 g

Codeine sulphate 0.015 g

Belladonna extract 0.010 g

Prepare capsules.

Comment: In this prescription aminopyrine and acetyl salicylic acid form eutectic mixture
and wetting of belladonna extract give green colour.

Remedy: Light magnesium oxide (approximately 65 mg) may be added. The half quantity of
magnesium oxide is mixed with aminopyrine and the other half with acetyl salicylic acid
separately. The two are mixed gently and then other ingredients are added and mixed gently.

3.CHEMICAL INCOMPATIBILITY

Chemical incompatibilities are generally caused by pH change, a double decomposition

reaction or complex formation.

Precipitate yielding interactions

Two ingredients may produce precipitation after reaction in a solution.

Method – A

All or most of the vehicles are divided into two portions. The reactants are dissolved in
separate portions of vehicles. One portion is mixed with the other while stirring rapidly. This
method will produce generally, lighter, more difussible precipitate. Portion –I

Dissolve 50 ml reactant ‘A’

Vehicle Final100ml preparation

Portion-II

Dissolve 50ml reactant ‘B’

Method-B

This method is used for bulky indiffusible precipitates. In this case bulky precipitates will be
suspended and stabilized by adding thickening agents.

The vehicle is derived into two portions. In one portion one of the reactant is dissolved.

The other portion is used to prepare tragacanth mucilage (2 g per 100ml final preparation).
The second reactant is dissolved in the tragacanth mucilage.

The first solution is then added to the mucilage.

Portion I

Add Final 50ml reactant ‘A’

Product

Vehicle100 ml

Portion-II

Prepare tragacanth mucilage Add reactant B

50ml with the vehicle the mucilage

pH EFFECT

Modern drugs are often salts of weak acids and weak bases.

These salts are usually soluble in water while free bases are practically insoluble.

Consequently, if a solution of a salt of weak acid is acidified the free weak acid may

precipitate out.Similarly, if a solution of a salt of weak base is made alkaline the free

weak base may precipitate out.

 Salt of weak acid + acid → Free acid 

Salt of weak base + alkali → Free base 

Whether precipitation occurs or not depends on –

(a) The solubility of the unionized acid or base,

(b) The pH of the solution

(c) The dissociation constant Ka of the acid or base.

Solubility of the unionized acid or base

1. Alkaloids

2. Other weak bases

3. Barbiturates

4. Other weak acids

1. ALKALOIDS

1.Alkaloids are weak bases. They are almost insoluble in water.

2.Salts of alkaloids are soluble in water.

3.If these salts are dispensed with alkaline preparations or substances then free alkaloid may
be precipitated.

The alkaline preparations those are generally incorporated with alkaloidal salt solutions are

(i) Aromatic Ammonia Solution

(ii) Strong Ammonium Acetate Solution

(iii)Ammonium bicarbonate

(iv)Sodium bicarbonate

However, if the alkaloidal salts are taken in low concentration then this problem does not
occur because all alkaloids (free base) are slightly soluble in water.

Example- Nux vomica and Alkali Mixture

This preparation contains Nux vomica Tincture and Sodium bicarbonate (NaHCO3)

Remedy: If small amount of nux vomica tincture is taken then amount of free alkaloid

base in the final preparation will remain within the solubility limit of the alkaloid. In this
preparation contains only 5% Nux-vomica Tincture.
 Given below are some of the alkaloid solutions used as source to some alkaline

preparations:

Alkaloidal preparation Alkaloids present Maximum volume (in %) of alkaloidal

preparation that can be added to alkaline
(solubilityin water) preparation (without any precipitation)

NuxVomica Tincture BPC Strychnine 10

(1 in 7000parts)

(i(i)Morphine hydrochloride Morphine 2.5

solution
(1 in 5000 parts)
(i(ii)Opium Tincture
Morphine 1.8
(i(iii)Camphorated Opium
Tincture Morphine 37.5

(v(iv)Chloroform and
Morphine Tincture Morphine 10.0

Belladonna, Hyoscyamus Solanaceous alkaloids

and Stramonium Tinctures
Atropine (1 in 400) Unlimited

Hyoscyamine (1 in
280)

Ipecacuanha Tincture Emetine 66.7

(1 in 1000 parts)

Cocaine hydrochloride Cocaine Very small amount

preparations

2. OTHER WEAK ALKALOIDS

Other organic weak bases of low solubility, which may be precipitated under alkaline

conditions, include the

Local anaesthetics – amethocaine and cinchocaine

Analgesic – methadone
3. BARBITURATES

►The derivatives of barbituric acid are almost insoluble in water, but their sodium salts are
soluble.

►These soluble salts are occasionally prescribed in mixture (liquid).

Incompatibility Solutions of the salts are very alkaline and are incompatible with

acids, acidic salts (e.g. ammonium bromide) and acidic syrups (e.g.. lemon syrup)

In presence of these acidic ingredients the insoluble barbituric acid derivative will

precipitate.

►This precipitate can neither be re-dispersed nor suspended satisfactorily

with thickening agents.

Remedy When precipitation is likely, it is preferable to substitute the chemically

equivalent amount of the corresponding insoluble barbituric acid derivative which ca

be suspended easily with thickening agent.

4.OTHER WEAK ACIDS

Sulfonamides are weak acids in unionized form and their solubility is less.

Incompatibility-In presence of acid or acidic salts the unionized form may be precipitated.

Remedy- Sulfonamide salts and the acidic ingredients are dissolved in separate amount

of vehicle. With one portion tragacanth mucilage is prepared and the other portion is

suspended in it.

Double decomposition

1. ALKALOIDAL SALTS WITH SOLUBLE IODIDES

Alkaloidal salts will react with soluble iodides and may precipitate insoluble iodide salts of
alkaloids.

Alklaoidal salts Soluble iodide

Emetine hydrochloride

Methadome hydrochloride Potassium iodide

Strychnine hydrochloride
 Papaverine hydrochloride

Incompatibility

Emetine-HCl + KI → Emetine-HI + KCl

Solubility of Emetine-HI is less hence may precipitate.

Example: Potassium iodide is used as expectorant in some alkaloid containing cough

mixtures.

Remedy: If the alkaloid concentration is very low then precipitation does not occur.

2. ALKALOIDAL SALTS WITH TANNINS

Incompatibility:

Alkaloidal salts + tannins → Alkaloidal tannates

N.B. One advantage of this reaction is in case of alkaloidal poisoning strong tea (or tannic
acid solution) is used to precipitate the alkaloids.

Remedy: Method-B (suspended with the help of tyragacanth mucilage) is used to suspend the
precipitate.

3. SOLUBLE BARBITURATES WITH AMMONIUM BROMIDE

Incompatibility

e.g. Phenobarbitone-Na + NH4Br → Phenobarbitone + NaBr + NH3.

Remedy: NH4Br is an acidic salt; i.e. it is providing the necessary H+ to phenobarbitone-Na.

So NH4Br is replaced with sodiumbromide (NaBr).

N.B. Phenobarbitone is barbituric acid derivative. Bromide ion (Br–) has sedative action.

4.GAS PRODUCTION

Incompatibility

Carbonates + Acid or → CO2

Or

bicarbonates acidic drugs

Remedy:

The ingredients are mixed in a wide mouthed mortar and left until effervescence has ceased.
If the rate of reaction is slow it is hastened by using hot vehicle.

Example (a)
Ammonium carbonate Squill Syrup or Or + Squill
oxymel or → CO2

Ammonium bicarbonate Vinegar Squill

All of these squill preparations contain acetic acid. This acetic acid reacts with NH4CO3 or
NH4(HCO3) to produce CO2.

Remedy:

(i)Substitution of Squill preparation with neutral squill tincture or,

(ii)Wait for effervescence to complete then poured in an container.

e.g.(b) Borax, sodium bicarbonate and glycerol

Incompatibility

Borax is hydrolysed to boric acid.

Boric acid reacts with glycerol to produce glycerol-boric acid, which liberates CO2 from
bicarbonate.

Remedy:

The reaction is hastened by addition of hot water.

Example (c) Alkali bicarbonates with soluble calcium and magnesium salts.

CaCl2 + 2NaHCO3 → CaCO3 + CO2 + 2NaCl + H2O

Remedy:

These carbonates are readily diffusible hence Method A is followed.

i.e. (i) CaCl2 is dissolved in ½ portion of the hot vehicle.

(ii) NaHCO3 is dissolved in ½ portion of the hot vehicle.

(iv) NaHCO3 solution is added to CaCl2 solution. So the reaction will be fast, CO2

release will be rapid. CaCO3 will be diffusible.

5. LIQUORICE LIQUID EXTRACT IN ACID MEDIA

This extract (Yastimadhu) contains glycyrrhizin, a sweet substance, consisting of potassium

and sodium salts of glycyrrhizinic acid.

Incompatibility

K salt of glycyrrhizinic acid + acid media → Free glycyrrhizinic acid

Free glycyrrihizininc acid forms a sticky, blask sediment that is difficult to diffuse. Further
the insoluble substances are tasteless, hence the flavor is lost.

Remedy:

The extract should be prescribed in neutral or alkaline solutions only.

6.POTASSIUM CHLORATE AND OXIDIZABLE SUBSTANCES

Incompatibility :

Potassium chlorate+sulfur or organic compounds or Explosion readily oxidizable substances

Triturated or heated in dry condition in contact with charcoal.

N.B. Potassium chlorate, sulfur and charcoal are the common ingredients of fire crackers.

Remedy:

1.Mixing of dry substances is inadvisable but, if essential, the ingredients should be

powdered separately in a mortar, and then all the ingredients are taken on an ointment plate
and mixed gently with a spatula. Any type of friction is avoided. Potassium chlorate is
powdered in a scrupulously clean mortar.

2. The tablets should be supplied in rigid containers with a warning to the patient not to carry
them loose in a pocket or handbag, because of the risk of catching fire from contact with
matches or surfaces containing phosphorous compounds.

pH and pKa

Unionized form of a weakly acidic or weakly basic compound is less soluble in water than its
ionized form. How much amount of the compound will remain in ionized or unionized state
depends on Handerson-Hasselbach equation:

If the compound is a weak acid:

Example HA+ H2O= A– +H3O+.

Acid Corresponding base

(Unionized) (Ionized)
 UNIT 5:

SEMISOLID DOSAGE FORMS:

SEMISOLID DOSAGE FORMS

►Semisolid dosage forms are products of semisolid consistency and applied to skin or
mucous membranes for therapeutic or protective action or cosmetic function.

►Semisolids constitute a significant proportion of pharmaceutical dosage forms.

►They serve as carriers for drugs that are topically delivered by way of the skin, cornea,
rectal tissue, nasal mucosa, vagina, buccal tissue, urethral membrane and external ear lining.

►A wide range of raw materials is available for the preparation of a semisolid dosage form.

►Apart from the usual pharmaceutical ingredients such as preservatives, antioxidants and
solubilizers, the basic constituents of a semisolid dosage form are unique to its composition
the choice of suitable raw materials for a formulation development is made on the basis of the
drug delivery requirements and the particular need to impart sufficient emolliency or other
partially -medicinal qualities in the formulation.

Advantage of semi-solid dosage form

►It is used externally.

►Probability of side effects is reduced.

►Reliable Local action.

Disadvantage of semi-solid dosage form

►There is no dosage accuracy in this type of dosage form.

►The base which is used in the semi-solid dosage form can be easily oxidized.

►If we go out after using semi-solid dosage form problems occur.

IDEAL PROPERTIES OF SEMISOLID DOSAGE FORMS

Physical properties:

►It should have smooth texture.

►It has to be elegant in appearance.

►It should be non dehydrating.

►It should be non gritty.

►It should show the property of non greasy and non staining.
► It should be non hygroscopic in nature.

Physiological properties:

►It has to be non irritating property.

►Do not alter membrane / skin functioning

►Miscible with skin secretion

►Have low sensitization effect

Application properties:

►Easily applicable with efficient drug release.

►High aqueous wash ability.

MECHANISM OF DRUG PENETRATION

SKIN

Function of Skin: Skin performs the following functions:

1.Protection: An anatomical barrier from pathogens and damage between the internal and
external environment in bodily defense; Langerhans cells in the skin are part of the adaptive
immune system.

2.Sensation: Contains a variety of nerve endings that react to heat and cold, touch, pressure,
vibration and tissue injury.

3. Heat regulation: The skin contains a blood supply far greater than its requirements which
allows precise control of energy loss by radiation, convection and conduction.

4. Control of evaporation: The skin provides a relatively dry and semi-impermeable barrier
to fluid loss.

5. Aesthetics and communication: others see our skin and can assess our mood, physical
state and attractiveness.

6.Storage and synthesis: Acts as a storage center for lipids and water, as well as a means of
synthesis of vitamin D by action of UV on certain parts of the skin.

7. Excretion: Sweat contains urea, however its concentration is 1/130th that of urine,
hence excretion by sweating is at most a secondary function to temperature regulation.

8.Absorption: The cells comprising the outermost 0.25–0.40 mm of the skin are "almost
exclusively supplied by external oxygen", although the "contribution to total respiration is
negligible". In addition, medicine can be administered through the skin, by ointments or by
means of adhesive patch, such as the nicotine patch oriontophoresis. The skin is an important
site of transport in many other organs.

9. Water resistance: The skin acts as a water resistant barrier so essential nutrients are not
washed out of the body.
STRUCTURE OF SKIN

►The skin has three main layers: the epidermis, dermis and hypodermis.

►Epidermis is the outermost layer. It consists of:

(a) The basal layer (innermost) is one cell thick layer: Its cells divide constantly and the
daughter cells are steadily pushed towards the surface.

(b)The prickle cell layer: The cells in this region are linked by tiny bridges or prickles.

(c)The granular layer: When they reach this region, the upwardly moving cells become
granules and begin to synthesize the inert protein keratin.

(d) The horny layer (stratum corneum): This is the outermost layer and the cells are
heavily keratinized and dead. The dead cells sloughs off gradually.

►Dermis is the middle and the main part of the skin. The dermis is made up of protein
collagen and elastin. The collagen is in the form of gel that is reinforced by a framework of
elastin.

►Dermis contains the following structures:

(a)Blood vessels, lymphatics tissues and nerves.

(b)Epidermal appendages e.g. hair follicles, sebaceous glands and sweat glands.

►Hypodermis, the innermost layer, consists of adipose tissues. It gives physical protection
and thermal insulation to underlying structures.
[Epidermis is non-granular but is penetrated by hair follicles, sebaceous glands and sweat
glands.

Sebum is the secretion of sebaceous glands. Sebum is a mixture of fatty substances and
emulsifiers; it mixes with water producing a fluid of pH 5.5 that covers the skin surface and
permeates the upper layer of keratinized cells – this is called the “acid-mantle” of skin.

Keratin is hydrophillic; the stratum corneum normally contains about 20% w/w of water, the
amount varying with atmospheric humidity. This moisture keeps the skin supple and if its
level falls below about 12% the cells becomes dry and brittle and then shrink and curl at the
edges, making the skin feel rough.

Cracking may follow, causing discomfort. Loss of water may be the result of excessive
evaporation, over-usage of detergents (which removes sebum) and cold weather (which
inhibits sebum production).]

►There are two pathways by which the drugs penetrate through the intact skin

1. Intercellular Pathway

Lipophilic drugs move in between the cells of stratum corneum.This is known as intercellular
pathway.

2.Intracellular(Transcellular)Pathway

Hydrophilic drugs and non-polar drugs move in between the cells of stratum corneum.This is
known as intracellular pathway.

Hair follicles and duct of sweat glands (which projects on the skin surface) have small
fractional areas that allow the entry of drug molecule into the skin. The movement of drug
molecules through these projections may be high in very stage of absoption,particularly for
lipophilic molecules and for those with least absorption stratum corneum.

Skin acts as a passive barrier to the diffusing drug molecules. The total diffusional resistance
encountered by the skin in the sum of the resistances offered by all its layers. The equation is
represented as follows,

R Skin=Rsc+Re+Rpd

R Skin=Total resistance of skin

Rsc=Diffusional resistance exerted by stratum corneum

Re= Diffusional resistance exerted by epidermis

Rpd = Diffusional resistance exerted by papillary of dermis

Among all three diffusional resistances,RSC is the strongest and passage through the stratum
corneum is the rate limiting step in percutaneous absorption.
Percutaneous drug absorption:

►Semisolid dosage forms for dermatological drug therapy are intended to produce desired
action at specific sites in the epidermal tissue.

►A drug’s ability to penetrate the skin’s epidermis, dermis and subcutaneous fat layers
depends on the properties of the drug and the carrier base. Although drug and the carrier base.

►The main portals of drug entry are the follicular region, the sweat ducts or the unbroken
stratum corneum between the appendages.

►A substance’s particular route mainly depends on the physicochemical properties of the

drug and the condition of the skin.

The mechanism by which the drug diffuses from skin is called passive diffusion process. It is
a non-mediated transport in which the drug molecules move into the deeper layers along their
concentration or electrochemical gradient, using their own kinetic energy. It can be best
explained by Fick’s first law of diffusion. According to Fick’s law, molecules diffuse from
higher concentration region to lower concentration region until equilibrium is achieved. The
diffusion rate or the rate of permeation of diffusing molecules across the various layers of
skin is given by the following mathematical equation.

dQ/dt=Ps[cd-cr]……………………..(1)

dQ/dt=Rate of drug diffusion or rate of permeation

Ps=Overall permeability coefficient of the skin tissues to the penetrant

cd=Concentration of drug in the donor phase(stratum corneum)

cr= Concentration of drug in the receptor phase(systemic circulation)

cd-cr=Concentration gradient.

In order to obtain a constant rate of drug permeation, it is necessary that the concentration of
the diffusant (drug)in the donor region(stratum corneum)should be greater than that in the
receptor region(systemic circulation).For the drug to diffuse it must be initially released from
its vehicle after which the drug penetrates the stratum corneum.Therefore,initially when the
drug is applied, its concentration is relatively high in the stratum corneum than in systemic
circulation. Under such circumstances equation(1) reduces to,

dQ/dt=Ps.cd [cd>>cr]………………………(2)

It is necessary to maintain the concentration of drug on the surface of stratum corneum (cd)
constant so that dQ/dt (rate of skin permeation) remains constant throughout the process. This
is possible when rate of delivery(rd)is greater than rate of absorption(ra) then concentration of
drug at donor phase is maintained at a level equel to or greater than the saturation solubility
in the stratum corneum[C cs].
Greater the saturation solubility, greater is the rate of penetration. The maximum rate of
penetration of drug molecule [dQ/dt]m through the skin is given by,

[dQ/dt]m=Ps. C cs

Some drug molecules bind within the strstum corneum and form drug depot.The remaining
drug diffuse into the deeper layers of the stratum corneum followed by partitioning into
viable epidermal layer.Once the drug diffuses into the stratum corneum,penetration into the
deeper layers is easily achieved.

Mechanism of Drug Penetration through the skin:

Drug

skin surface
Passive diffusion
Stratum corneum

Drug forms drug depot

Remaining drug molecules passively
Diffuses into
Viable epidermis

Remaining portion partitions into Dermis Passive diffusion

Partitions into Passive diffusion A fraction of drug Metabolized

Binds to receptor

Blood Subcutaneous Drugs binds Depot formation

Capillaries tissues to receptor

Systemic Drug depot

Circulation
Excretion.
FACTOR AFFECTING PERMEABILITY OF A DRUG THROUGH SKIN

A. Factor associated with the skin

(a)Hydration of the horny layer

►The hydration of keratinized cells is raised by covering the area with a moisture-proof
plastic film to prevent evaporation of perspiration. Hydration increases the drug penetration.

(b)Thickness of the horny layer

►The horny layer is thickest on palms and soles and thinnest on the face, penetration rate
increases with decreased thickness of horny layer.

(c)Skin condition

►The permeability of the skin is affected by age, disease, climate and injury.

For example, absorption occurs rapidly in children and if the dermis is exposed by a wound
or burn.

B.Factors associated with the medicament

(a)Solubility of the drug

►Highly lipid soluble molecules enter through hair follicles. Moderately lipid soluble
molecules penetrate directly across the horny layer.

(b)Dissociation constant (pKa)

►If a drug is ionized in the surrounding pH of the dermis then the penetration of the ionic
species are restricted by electrostatic interactions. Degree of ionization depends on the pKa of
the drug.

e.g. Methyl salicylate and methyl nicotinate penetrate much faster than salicylic acid and
nicotinic acid respectively.

(c)Particle size

Reducing the particle size increases the dissolution of a poorly soluble drug in suspension and
thus increases the release rate from the vehicle.

(d)Crystal structure

►The metastable polymorph is much more soluble than its stable form, so the release of drug
in metastable state is much faster than stable form.

C. Factors associated with vehicles

►The rate of release of a drug from a vehicle to stratum corneum is governed by vehicle-to-
stratum corneum partition coefficient.

►The thermodynamic activity of the drug in the vehicle is the product of the concentration
of the drug and the activity coefficient (g) of the drug in the vehicle. ►Drugs held firmly by
the vehicle exhibit low activity coefficient, hence slow rate of release from that drug-vehicle
combination.

►Drug held loosely by the vehicle shows higher activity coefficient, hence shows faster rate
of release.

►The vehicles may enhance the penetration of a drug in one or more of the following ways:-

a) By ensuring good contact with the surface of the body

b)By increasing the degree of hydration of the stratum corneum

c)By penetrating the epidermis

d)By directly altering the permeability of the skin

(a) Contact with body surface

►Sticky bases such as soft paraffin, Paraffin ointment B.P.C., Simple ointment B.P. etc.
adheres well to the skin but is difficult to apply evenly and remove completely.

►Creams are easier to apply and remove. Oil in water (o/w) creams mix with sebum and are
more suitable for weeping or wounded surface.

(b) Hydration of stratum corneum

►An occlusive layer reduces evaporation of water from skin, increasing hydration of the
horny layer and, therefore, promotes penetration of medicament.

e.g. hydrocarbons, wool fat and isopropyl myristate containing ointments produce occlusive
films on the skin. Water in oil (o/w) type creams has some occlusive effects.

►Humectants like glycerols are not good for retaining water because at low atmospheric
humidities, because they tend to increase loss of water by absorbing it from the skin.

(c) Penetration of the epidermis

►Bases miscible with the sebum penetrate into the regions of the skin in which sebum is
found.

e.g. Woolfat (originating from sebaceous glands of sheep) penetrates into the skin.

Vegetable oils penetrate more slowly and liquid paraffin does not penetrate at all.

(d) Alteration of skin permeability

►Penetration can be improved by dissolving the medicament in an organic liquid such as
ethanol, dimethylformamide(DMF), dimethyl acetamide, dimethylsulfoxide (DMSO) and
propylene glycol. They increases the hydration of skin.

TYPES OF SEMI SOLID DOSAGE FORM

Semisolid dosage forms are mainly divided into two categories as following

1. OINTMENTS

Definition: Ointments are semisolid preparations for application to the skin or mucosae. The
ointment base is almost always anhydrous and generally contains one or more medicaments
in suspension or solution.

Characteristics of an ideal ointment:

1. It should be chemically and physically stable.

2. It should be smooth and free from grittiness.

3. It should melt or soften at body temperature and be easily applied.

4. The base should be non-irritant and should have no therapeutic action.

5. The medicament should be finely divided and uniformly distributed throughout the base.
Classification of ointments

According to their therapeutic properties based on penetration of skin.

According to their therapeutic uses.

►Ointments classified according to their therapeutic properties based on penetration are as

follows:

(a) Epidermic, (b) Endodermic and (c) Diadermic

(a) Epidermic ointments:

►These ointments are intended to produce their action on the surface of the skin and produce
local effect.

►They are not absorbed.

►They acts as protectives, antiseptics and parasiticides.

(b) Endodermic ointments:

►These ointments are intended to release the medicaments that penetrate into the skin.

► They are partially absorbed and acts as emollients, stimulants and local irritants.

(c) Diadermic ointments:

►These ointments are intended to release the medicaments that pass through the skin and
produce systemic effects.

►According to therapeutic uses the ointments are classified as follows:

(i) Acne treatment :resorcinol, sulfur.

(ii) Antibiotics :Used to kill microorganisms.

e.g. bacitracin, chlortetracycline, neomycin.

(iii) Antieczematous :Used to stop oozing and exudation from vesicles on the

skin.

e.g. hydrocortisone, coal tar, ichthamol, salicylic acid.

(iv) Antifungal :Used to inhibit or kill the fungi.

e.g. benzoic acid, salicylic acid, nystatin, clotrimazole, etc.

(v) Anti-inflammatory :Used to relieve inflammatory, allergic and pruritic conditions of the
skin
 e.g. betamethasone valerate, hydrocortisone, triamcinolone

acetonide

(vi) Antipruritic :Used to relieve itching.

e.g. benzocaine, coal tar.

(vii) Antiseptic :Used to stop sepsis.

e.g. ammoniated mercury, zinc oxide.

(vii) Astringent :Reduces the secretion of glands or discharge from skin

surface.

e.g. calamine, zinc oxide, aluminium acetate and tannic

acid.

(ix) Counter irritan :These are applied locally to irritate the intact skin, thus reducing or
relieving another irritation or deep seated pain. e.g. capsicum oleoresin, iodine (Iodex),
methyl salicylate.

(x) Dandruff treatment :e.g. salicylic acid and cetrimide (cetyl trimethyl

ammonium bromide)

(xi) Emollient :Used to soften the skin (for example in the dry season).

e.g. soft paraffin

(xii) Keratolytic :Used to remove or soften the horny layer of the skin.

e.g. resorcinol, salicylic acid and sulfur.

(xi) Keratoplastic :Tends to increase the thickness of horny layer e.g. coal tar.

(xii) Parasiticide :These ointments destroy or inhibit living infestations such

as lice and ticks.

e.g. benzyl benzoate, gamma-benzene hexachloride (GBH),

sulfur etc.

(xiii) Protective :Protects the skin from moisture, air, sun rays or other

substances such as soaps or chemicals.

e.g. silicones, titanium dioxide, calamine, zinc oxide,

petrolatum.
OINTMENT BASES

The ointment base is that substance or part of an ointment preparation which serves as carrier
or vehicle for the medicament.

An ideal ointment base should be

►Inert,

►Stable,

►Smooth,

►Compatible with the skin,

►Non-irritating and

►Should release the incorporated medicaments readily.

Classification of ointment bases:

1.Oleaginous bases

2.Absorption bases

3.Water-miscible bases

4.Water soluble bases

1.Oleaginous bases

►These bases consists of oils and fats. The most important are the Hydrocarbons i.e.
petrolatum, paraffins and mineral oils.

►The animal fat includes lard.

►The combination of these materials can produce a product of desired melting point and
viscosity.

(a) Petrolatum (Soft paraffin)

►This is a purified mixture of semi-solid hydrocarbons obtained from petroleum or heavy

lubricating oil.

Yellow soft paraffin (Petrolatum; Petroleum jelly)

►This a purified mixture of semisolid hydrocarbons obtained from petroleum. It may contain
suitable stabilizers like, antioxidants e.g. α-tocopherol (Vitamin E), butylated hydroxy
toluene (BHT) etc.

Melting range : 38 to 560C.

White soft paraffin (White petroleum jelly, White petrolatum)

►This a purified mixture of semisolid hydrocarbons obtained from petroleum and wholly or
partially decolorized by percolating the yellow soft paraffin through freshly burned bone
black or adsorptive clays.

Melting range : 38 to 560C.

Use: The white form is used when the medicament is colourless, white or a pastel shade. This
base is used in

Dithranol ointment B.P.

Ammoniated Mercury and Coal tar ointment B.P.C.

Zinc ointment B.P.C.

(b) Hard paraffin (Paraffin)

►This is a mixture of solid hydrocarbons obtained from petroleum.

►It is colourless or white, odorless, translucent, wax-like substance.

►It solidifies between 50 and 570C and is used to stiffen ointment bases.

(c) Liquid paraffin (Liquid petrolatum,; White mineral oil)

►It is a mixture of liquid , hydrocarbons obtained from petroleum.

►It is transparent, colourless, odourless, viscous liquid.

►On long storage it may oxidize to produce peroxides and therefore, it may contain
tocopherol or BHT as antioxidants.

►It is used along with hard paraffin and soft paraffin to get a desired consistency of the
ointment.

►Tubes for eye, rectal and nasal ointments have nozzles with narrow orifices through which
it is difficult to expel very viscous ointments without the risk of bursting the tube.

►To facilitate the extrusion upto 25% of the base may be replaced by liquid paraffins.

Advantages of hydrocarbons bases:

(i)They are not absorbed by the skin. They remain on the surface as an occlusive layer that
restricts the loss of moisture hence, keeps the skin soft.

(ii)They are sticky hence ensures prolonged contact between skin and medicament.

(iii)They are almost inert. They consist largely of saturated hydrocarbons, therefore, very few
incompatibilities and little tendency of rancidity are there.
(iv) They can withstand heat sterilization; hence, sterile ophthalmic ointments can be
prepared with it.

(v) They are readily available and cheap.

Disadvantages of hydrocarbon bases:

(i)It may lead to water logging followed by maceration of the skin if applied for a prolonged
period.

(ii)It retains body heat, which may produce an uncomfortable feeling of warmth.

(iii)They are immiscible with water; as a result rubbing onto the surface and removal after
treatment both are difficult.

(iv)They are sticky, hence makes application unpleasant and leads to contamination of
clothes.

(v)Water absorption capacity is very low, hence, these bases are poor in absorbing exudate
from moist lesions.

2. Absorption bases

►The term absorption base is used to denote the water absorbing or emulsifying property of
these bases and not to describe their action on the skin.

►These bases (some times called emulsifiable ointment bases) are generally anhydrous
substances which have the property of absorbing (emulsifying) considerable quantity of water
yet retaining its ointment-like consistency.

►Preparations of this type do not contain water as a component of their basic formula but if
water is incorporated a W/O emulsion results.

Wool Fat (anhydrous lanolin)

It is the purified anhydrous fat like substance obtained from the wool of sheep.

●It is practically insoluble in water but can absorb water upto 50% of its own weight.
Therefore it is used in ointments the proportion of water or aqueous liquids to be incorporated
in hydrocarbon base is too large.

●Due to its sticky nature it is not used alone but is used along with other bases in the
preparation of a number of ointments.

e.g. Simple ointment B.P. contains 5% and the B.P. eye ointment base contains 10% woolfat.

Hydrous Wool Fat (Lanolin)

● It is a mixture of 70 % w/w wool fat and 30 % w/w purified water. It is a w/o emulsion.
Aqueous liquids can be emulsified with it.
● It is used alone as an emollient. Example:- Hydrous Wool Fat Ointment B.P.C., Calamine
Coal Tar Ointment.

Wool Alcohol

It is the emulsifying fraction of wool fat. Wool alcohol is obtained from wool fat by treating
it with alkali and separating the fraction containing cholesterol and other alcohols. It contains
not less than 30% of cholesterol.

Use:

●It is used as an emulsifying agent for the preparation of w/o emulsions and is used to absorb
water in ointment bases.

●It is also used to improve the texture, stability and emollient properties of o/w emulsions.
Examples: - Wool alcohol ointment B.P. contains 6% wool alcohol and hard, liquid and soft
paraffin.

Beeswax

It is purified wax, obtained from honey comb of bees.

It contains small amount of cholesterol. It is of two types: (a) yellow beeswax and (b) white
beeswax.

Use:

Beeswax is used as a stiffening agent in ointment preparations.

Examples:-Paraffin ointment B.P.C. contains beeswax.

Cholesterol

●It is widely distributed in animal organisms. Wool fat is also used as a source of cholesterol.

Use: It is used to increase the water absorbing power of an ointment base.

Example: Hydrophilic petroleum U.S.P. contains:

Cholesterol 3%

Stearyl alcohol 3%

White beeswax 8%

White soft paraffin 86%

Advantages of absorption bases:

(i) They are less occlusive nevertheless, are good emollient.

(ii)They assist oil soluble medicaments to penetrate the skin.

(iii)They are easier to spread.

(iv)They are compatible with majority of the medicaments.

(v) They are relatively heat stable.

(vi)The base may be used in their anhydrous form or in emulsified form.

(vii)They can absorb a large quantity of water or aqueous substances.

Disadvantages:

● Inspite of their hydrophilic nature, absorption bases are difficult to wash.

3. WATER MISCIBLE BASES

►They are miscible with an excess of water. Ointments made from water-miscible bases are
easily removed after use.

There are three official anhydrous water-miscible ointment bases:-

Example:-

Emulsifying ointment B.P.-contains anionic emulsifier.

Cetrimide emulsifying ointment B.P.-contains cationic emulsifier

Cetomacrogol emulsifying ointment B.P.-contains non-ionic emulsifier

Uses:

●They are used to prepare o/w creams and are easily removable ointment bases

e.g. Compound Benzoic Acid Ointment (Whitfield’s Ointment)-used as antifungal ointment.

Advantages of water miscible bases:

(i)Readily miscible with the exudates from lesions.

(ii)Reduced interference with normal skin function.

(iii)Good contact with the skin, because of their surfactant content.

(iv)High cosmetic acceptability, hence there is less likelihood of the patients discontinuing
treatment.

(v)Easy removal from the hair.

4. WATER SOLUBLE BASES

►Water soluble bases contain only the water soluble ingredients and not the fats or other
greasy substances, hence, they are known as grease-less bases.
►Water soluble bases consists of water soluble ingredients such as polyethylene glycol
polymers (PEG) which are popularly known as “carbowaxes” and commercially known as
“macrogols”.

They are a range of compounds with the general formula:

CH2OH . (CH2OCH2) n CH2OH

►The PEGs are mixtures of polycondensation products of ethylene and water and they are
described by numbers representing their average molecular weights. Like the paraffin
hydrocarbons they vary in consistency from viscous liquids to waxy solids.

Example:-

Macrogols 200, 300, 400 - Viscous liquids

Macrogols 1500 - Greasy semi-solids

Macrogols 1540, 3000, 4000, 6000 - Waxy solids.

Different PEGs are mixed to get an ointment of desired consistency.

Advantages of PEGs as ointment base:

(a)They are water soluble; hence, very easily can be removed from the skin and readily
miscible with tissue exudates.

(b)Helps in good absorption by the skin.

(c) Good solvent properties. Some water-soluble dermatological drugs, such as salicylic acid,
sulfonamides, sulfur etc. are soluble in this base.

(d)Non-greasy.

(e)They do not hydrolyze, rancidify or support microbial growth.

(f)Compatibility with many dermatological medicaments.

Disadvantages:

(a)Limited uptake of water. Macrogols dissolve when the proportion of water reaches about
5%.

(b)Reduction in activity of certain antibacterial agents, e.g. phenols, hydroxybenzoates and

quaternary compounds.

(c)Solvent action on polyethylene and bakelite containers and closures.

Certain other substances which are used as water soluble ointment bases include tragacanth,
gelatin, pectin, silica gel, sodium alginate, cellulose derivatives, etc.
FACTORS GOVERNING SELECTION OF AN IDEAL OINTMENT BASE

1. Dermatological factors

2. Pharmaceutical factors

1. Dermatological factors

(a) Absorption and Penetration:

►‘Penetration’ means passage of the drug across the skin i.e. cutaneous penetration, and
‘absorption’ means passage of the drug into blood stream.

●Medicaments which are both soluble in oil and water are most readily absorbed though the
skin.

●Whereas animal and vegetable fats and oils normally penetrate the skin.

●Animals fats, e.g. lard and wool fat when combined with water, penetrates the skin.

● o/w emulsion bases release the medicament more readily than greasy bases or w/o
emulsion bases.

(b) Effect on the skin

►Greasy bases interfere with normal skin functions i.e. heat radiation and sweating.

►They are irritant to the skin.

►o/w emulsion bases and other water miscible bases produce a cooling effect due to the
evaporation of water.

(c) Miscibility with skin secretion and serum

►Skin secretions are more readily miscible with emulsion bases than with greasy bases. Due
to this the drug is more rapidly and completely released to the skin.

(d) Compatibility with skin secretions:

►The bases used should be compatible with skin secretions and should have pH about 5.5
because the average skin pH is around 5.5. Generally neutral ointment bases are preferred.

(e) Non-irritant

All bases should be highly pure and bases specially for eye ointments should be non-irritant
and free from foreign particle.

(f) Emollient properties

►Dryness and brittleness of the skin causes discomfort to the skin therefore, the bases should
keep the skin moist.
►For this purpose water and humectants such as glycerin, propylene glycol are used.
Ointments should prevent rapid loss of moisture from the skin.

(g) Ease of application and removal

►The ointment bases should be easily applicable as well as easily removable from the skin
by simple washing with water.

►Stiff and sticky ointment bases require much force to spread on the skin and during
rubbing newly formed tissues on the skin may be damaged.

2. Pharmaceutical factors

(a) Stability

►Fats and oils obtained from animal and plant sources are prone to oxidation unless they are
suitably preserved.

►Due to oxidation odour comes out. This type of reactions are called rancidification. ►
Lard, from animal origin, rancidify rapidly.

►Soft paraffin, simple ointment and paraffin ointment are inert and stable.

► Liquid paraffin is also stable but after prolonged storage it gets oxidized.

► Therefore, an antioxidant like tocopherol (Vit -E) may be incorporated.

►Other antioxidants those may be used are butylated hydroxy toluene (BHT) or butylated
hydroxy hydroxy anisole (BHA).

(b) Solvent properties

►Most of the medicaments used in the preparation of ointments are insoluble in the ointment
bases therefore, they are finely powdered and are distributed uniformly throughout the base.

(c) Emulsifying properties

►Hydrocarbon bases absorbs very small amount of water.

►Wool fat can take about 50% of water and when mixed with other fats can take up several
times its own weight of aqueous solution.

►Emulsifying ointment, cetrimide emulsifying ointment and cetomacrogol emulsifying

ointment are capable of absorbing considerable amount of water, forming w/o creams.

(d) Consistency

►The ointments produced should be of suitable consistency.

►They should neither be hard nor too soft.

► They should withstand climatic conditions.

► Thus in summer they should not become too soft and in winter not too hard to be difficult
to remove from the container and spread on the skin.

►The consistency of an ointment base can be controlled by varying the ratio of hard and
liquid paraffin.

PREPARATION OF OINTMENTS

►There are four methods are there namely Trituration, Fusion, Chemical reaction and
Emulsification methods. Apart from that two methods are frequently used in preparation
ointments namely Fusion, Trituration methods.

1. Ointments prepared by Fusion method:When an ointment base contain a number of

solid ingredients such as white beeswax, cetyl alcohol, stearyl alcohol, stearic acid, hard
paraffin, etc. as components of the base, it is required to melted them. The melting can be
done in two methods:

Method-I

The components are melted in the decreasing order of their melting point i.e. the higher M.P.
substance should be melted first, the substances with next melting point and so on. The
medicament is added slowly in the melted ingredients and stirred thoroughly until the mass
cools down and homogeneous product is formed.

Advantages:This will avoid over-heating of substances having low melting point.

Method-II

►All the components are taken in subdivided state and melted together.

Advantages:

The maximum temperature reached is lower than Method-I, and less time was taken possibly
due to the solvent action of the lower melting point substances on the rest of the ingredients.

Example: Simple ointment B.P. contains

Wool fat 50g

Hard paraffin 50g

Cetostearyl alcohol 50g

White soft paraffin 850g

Procedure:Hard paraffin and cetostearyl alcohol on water-bath. Wool fat and white soft
paraffin are mixed and stirred until all the ingredients are melted.If required decanted or
strained and stirred until cold and packed in suitable container.
2. Ointment Prepared By Trituration:This method is applicable in the base or a liquid
present in small amount.

(i)Solids are finely powdered are passed through a sieve (# 250, # 180, #125).

(ii)The powder is taken on an ointment-slab and triturated with a small amount of the base. A
steel spatula with long, broad blade is used. To this additional quantities of the base are
incorporated and triturated until the medicament is mixed with the base.

(iii) Finally liquid ingredients are incorporated. To avoid loss from spread, a small volume of
liquid is poured into a depression in the ointment an thoroughly incorporated before more is
added in the same way. Spreading is more easily controlled in a mortar than on a tile.

Example:(i) Whitfield ointment (Compound benzoic acid ointment B.P.C.)

Formula: Benzoic acid, in fine powder 6gm

Salicylic acid, in fine powder 3gm

Emulsifying ointment 91gm

Method: Benzoic acid and salicylic acid are sieved through No. 180 sieves. They are mixed
on the tile with small amount of base and levigated until smooth and dilute gradually.

3. Ointment Preparation By Chemical Reaction:Chemical reactions were involved in the

preparation of several famous ointments of the past, e.g. Strong Mercuric Nitrate Ointment.

(a) Ointment containing free iodine

Iodine is only slightly soluble in most fats and oils but readily soluble.

Iodine is readily soluble in concentrated solution of potassium iodide due to the formation of
molecular complexes KI.I2, KI.2I2, KI.3I2 etc.

These solutions may be incorporated in absorption-type ointment bases.

e.g. Strong Iodine Ointment B.Vet.C (British Veterinary Pharmacopoeia) is used to treat
ringworm in cattle. It contains free iodine. At one time this type of ointments were used as
counter-irritants in the treatment of human rheumatic diseases but they were not popular
because:

(i)They stain the skin a deep red color.

(ii)Due to improper storage the water dries up and the iodine crystals irritate the skin, hence
glycerol was some times to dissolve the iodine-potassium iodide complex instead of water.

Example: Strong Iodine Ointment B. Vet.C.

Iodine

Woolfat
 Yellow soft paraffin

Potassium iodide

Water

Procedure:

(i) KI is dissolved in water. I2 is dissolved in it.

(ii)Wool fat and yellow soft paraffin are melted together over water bath. Melted mass is
cooled to about 400C.

(iii) I2 solution is added to the melted mass in small quantities at a time with continuos
stirring until a uniform mass is obtained.

(iv)It is cooled to room temperature and packed.

Use: - To destroyed Ringworm in cattle.

(b) Ointment containing combined iodine

Fixed oils and many vegetable and animal fats absorb iodine which combines with the double
bonds of the unsaturated constituents, e.g.

CH3. (CH2) 2.CH = CH.(CH2) 7.COOH + I2 → CH3.(CH2) 2.CHI CHI.(CH2) 7.COOH

Oleic acid di-iodostearic acid

Example: Non-staining Iodine Ointment B.P.C. 1968

Iodine

Arachis Oil

Yellow Soft Paraffin

Method

(a)Iodine is finely powdered in a glass mortar and required amount is added to the oil in a
glass-stoppered conical flask and stirred well.

(b)The oil is heated at 500C in a water-bath and stirred continually. Heating is continued until
the brown color is changed to greenish-black, this may take several hours.

(c) From 0.1g of the preparation the amount of iodine is determined by B.P.C. method and
the amount of soft paraffin base is calculated to give the product the required strength.

(d)Soft paraffin is warmed to 400C. The iodized oil is added and mixed well. No more heat is
applied because this causes deposition of a resinous substance.
(e)The preparation is packed in a warm, wide-mouthed, amber color, glass bottle. It is
allowed to cool without further stirring.

4. Preparation Of Ointments By Emulsification:An emulsion system contain an oil phase,

an aqueous phase and an emulsifying agent.

For o/w emulsion systems the following emulsifying agents are used:

(i) water soluble soap

(ii) cetyl alcohol

(iii)glyceryl monostearate

(iv) combination of emulsifiers: triethanolamine stearate + cetyl alcohol

(v)non-ionic emulsifiers: glyceryl monostearate, glyceryl monooelate, propylene

glycol stearate

For w/o emulsion creams the following emulsifiers are used:

(i) polyvalent ions e.g magnesium, calcium and aluminium are used.

(ii) combination of emulsifiers: beeswax + divalent calcium ion

The viscosity of this type of creams prevents coalescence of the emulsified phases and helps
in stabilizing the emulsion.

Example:Cold cream

Procedure:

(i) Water immiscible components e.g. oils, fats, waxes are melted together over water bath
(700C).

(ii) Aqueous solution of all heat stable, water soluble components are heated (700C).

(iii)Aqueous solution is slowly added to the melted bases with continuous stirring until the
product cools down and a semi-solid mass is obtained.

(The aqueous phase is heated otherwise high melting point fats and waxes will immediately
solidify on addition of cold aqueous solution.)
EVALUATION OF OINTMENTS

The different methods of evaluation of ointments are

(1) Physical methods

►Test of rate of absorption

►Test of non-irritancy

►Test of rate of penetration

►Test of rate of drug release

►Test of rheological properties

►Test of content uniformity

(2) Microbiological methods

►Test of microbial content

►Test of preservative efficacy

PHYSICAL METHODS

Test of rate of absorption

Diadermic ointments are those from which the drug moves into deeper skin tissues and
finally into the systemic circulation.Such ointments should be evaluated for the rate of
absorption of drugs. The ointment should be applied over a definite area of the skin by
rubbing. At regular intervals of time, serum and urine samples should be analysed for the
quantity of drug absorbed.The rate of absorption i.e., the amount of drug absorbed per unit
time should be more.

Test of non-irritancy

The bases used in the formulation of ointments may cause irritation or allergic reactions. on-
irritancy of the preparation is evaluated by patch test. In this test 24 human volunteers are
selected.Definite quantity of ointment is applied under occlusion daily on the back or volar
forearm for 21 days. Daily the type of pharmacological action observed is noted. No visible
reaction or erythema or intense erythema with edema and vesicular erosion should occur. A
good ointment base shows no visible reaction.

Test of rate of penetration

The rate of penetration of a semisolid dosage form is crucial in the onset and duration of
action of the drug. Weighed quantity of the preparation should be applied over selected area
of the skin for a definite period of time. Then the preparation left over is collected and
weighed. The difference between the initial and the final weights of the preparation gives the
amount of preparation penetrated through the skin and this when divided by the area and time
period of application gives the rate of penetration of the preparation. The test should be
repeated twice or thrice. This procedure is tedious and not followed anymore.

Using flow-through diffusion cell or microdialysis method, the rate of penetration of the
preparation can be estimated. Animal or human skin of definite area should be collected and
tied to the holder present in a diffusion cell. The diffusion cell is placed in a fluid bath.
Measured quantity of the preparation is applied over the skin and the amount of drug passed
into the fluid is measured at regular intervals by analyzing the aliquots of fluid using a
spectrophotometer.

Test of rate of drug release

A clean test tube is taken and the internal surface is coated with the preparation as a thin
layer. Saline or serum is poured into the test tube. After a certain period of time, the saline is
analyzed for the quantity of the drug. The amount of drug when
divided by the time period gives the rate of drug release.

Test of rheological properties

The viscosity of the preparation should be such that the product can be easily removed from
the container and easily applied to the skin. Using cone and plate viscometer the viscosity of
the preparation is determined.

Test of content uniformity

The net weight of contents of ten filled ointment containers is determined. The results should
match each other and with the labelled quantity. This test is also called minimum fill test.

MICROBIOLOGICAL METHODS

Test of microbial content

Micro-organisms like pseudomonas aeruginosa and staphylococcus aureus may contaminate

the preparation and finally infect the skin. So ointments should be tested for the absence of
such micro-organisms.

Solutions of different samples of the preparation are made. Each sample is inoculated into
separate volumes of 0.5 ml of rabbit's plasma under aseptic conditions and incubated at 37
degrees C for 1-4 hours. No formation of the clot in the incubated mass indicates the absence
of the micro-organisms.

Test of preservative efficacy

Using pour plate technique the number of micro-organisms initially presents in the
preparation is determined. Solutions of different samples of the preparation are made and
mixed with Tryptone Azolectin (TAT) broth separately. All cultures of the micro-organisms
are added into each mixture, under aseptic conditions.
All mixtures are incubated. The number of micro-organisms in each sample is counted on
7th, 14th, 21st and 28th days of inoculation.

Microbial limits

On 14th day, the number of vegetative cells should not be more than 0.1% of initial
concentration.

On 28th day, the number of organisms should be below or equal to initial concentration.

PACKAGING OF OINTMENTS:

Ointment jars

Ointment jars come in a variety of different sizes and can be made of either colourless glass
or amber glass. Amber ointment jars are used for preparations that are sensitive to light.

They are used to package ointments and creams and can be used for individually wrapped
suppositories. As with cartons, additional care must be exercised in the storage of
preparations in ointment jars as they do not come with child-resistant closures.

Collapsible tubes

Collapsible tubes come in a variety of different sizes and can be used to package creams or
ointments. They are less convenient to fill than ointment jars and as such are rarely used for
individual patient formulations. They are more commonly utilised in small scale
manufacturing environments where a number of identical product are being manufactured at
the same time. As with ointment jars, additional care must be exercised in the storage of
collapsible tubes as they do not come with child-resistant closures.

Filling of Tubes

Small-scale and Large scale automatic filling machines are available which fill 60 tubes and
125 tubes per minute respectively.The tubes are filled from the open back end. The filled
plastic tubes are closed and sealed by heat and crimping. Metal tubes are sealed by folding
and crimping.

Storage

Filled containers are storedin a cool place to prevent separation of the product due to heat.

2. CREAMS

Creams are viscous liquid or semisolid emulsions intended for application to the skin i.e. for
external use.

Creams are of two types, aqueous creams and oily creams. In case of aqueous creams the
emulsions are oil-in-water type and in case of oily creams emulsions are of water-in-oil type.

Due to the presence of water soluble bases they can be easily removed from the skin.
The aqueous creams have a tendency to grow bacterial and mold growth, therefore a
preservative must be added in their formulation.

E.g. Cetomacrogol cream, Cetrimide cream, hydrocortisone cream, zinc cream BPC.

Advantages of creams

1. Creams are more acceptable to the patients because they are less greasy and are easier to
apply.

2. They interfere less with skin functions.

3. o/w type of creams (superior to w/o type) can be rub onto the skin more readily and are
easily removed by washing. w/o can be spread more evenly.

4. o/w type of cream are less likely to soil clothes.

5. Evaporation of water from o/w type of cream causes cooling sensation.

6.o/w creams absorbs the discharges from the wound (liquid exudate) very quickly.

7.w/o creams (e.g. cold creams) restricts evaporation from the skin, it can be used on non-
weeping surfaces to prevent dehydration ( in dry season), restore suppleness (softness) - this
property is said to be ‘emollient’.

Disadvantages of creams

1. Since it is a semisolid preparation and containing oil in large amount, some of which are
inedible, hence creams are not used for internal use. Basically creams are meant for
application onto the skin.

2. The aqueous phase is prone to the growth of molds and bacteria hence preservatives should
be used.

3. Sometimes rancidification of oils take place.

Calcification of creams

Creams

Aqueous creams/ oil water creams Oily creams / water in oil creams

Anionic creams Cationic creams Non-ionic creams Sterol Creams SoapCreams

►Creams are divided in to two types.

1.Aqueous creams/ oil water creams

These creams are composed of small droplets of oils which are dispersed in a continuous
aqueous phase. These are easy to handle when compared to oily creams. These creams are
less greasy and are more readily or easily washed off using water hence, they are more
acceptable. Basically, creams consist of three constituents i.e., oil phase, aqueous phase and
emulsifying agent.

Aqueous creams contain oil in water type emulsifying agents. Examples of emulsifying
agents are hydrophilic surfactants, monovalent soaps of fatty acids, tween (polyethylene
glycol derivative of sorbitan fatty acid).

When the aqueous creams are applied on the skin, the water soluble drug (present in it) gets
deposited on the skin after the evaporation of water from it. These creams are applied on
outermost part of the skin i.e., stratum corneum, which results in percutaneous absorption of
drug due to concentration gradient.

Depending upon the type of emulsifying agent used, aqueous creams are classified in to three
types.

a. Anionic creams
b. Cationic creams
c. Non-ionic creams
a.Anionic creams:

These creams are prepared by fusion method. The ingredients which are oily and waxy in
nature are melted together. The molten mixture is cooled to 60OC. aqueous solution (water) is
also warmed to 60OC and is poured in to the molten mixture with constant stirring. This
mixture is stirred to cool its temperature. A thermometer is used to get accurate results.

Examples:I. Prepare and dispense 50gr of phenoxyethanol aqueous cream B.P.

Ingredients Official amount Amount used

Phenoxyethanol 1g 0.5g
Emulsifying ointment 30g 15g
Purified water 69g 34.5g
Total gr 100g 50g

Method:

1.Phenoxyethanol is dissolved in hot purified water, which represents the aqueous solution.

2.Then the emulsifying ointment is melted and warmed to 60OC.

3.Aqueous solution of phenoxyethanol is then added to melted ointment with continuous

stirring.

4. Stirring is carried out until the preparation becomes cold.

5. The preparation is transferred in a suitable container, labeled and dispensed.

Directions for use: Apply on dry skin three times a day.

II. Prepare and dispense 50g of calamine cream BPC.

Ingredients Official amount Amount used

Calamine 4g 2g
Zinc oxide 3g 1.5g
Emulsifying wax 6g 3g
Arachis oil 40g 20g
Water 47g 23.5g
Total 100g 50g

Method:

1.Emulsifying wax is gently heated in order to melt it.

2.Arachis oil is added to the melted wax and warmed.

3.Water is added to the above preparation with continuous stirring, which is continued until
the preparation becomes cold.

4.Calamine and zinc oxide are triturated in the mortar and pestle with water.

5.The above mixture is then added to the preparation and stirred to obtain the cream.

6.It is transferred in a suitable container, labeled and dispensed.

Directions for use:Apply three times daily on the affected area.

b.Cationic creams

These creams are prepared by fusion method.

Examples:

i.Prepare 50g of cetrimide cream BP and dispense.

Ingredients Official amount Amount used

Cetrimide 0.5g 0.25g
Cetostearyl alcohol 5g 2.5g
Liquid paraffin 50g 25g
Purified water(boiled and 44.5 22.25
cooled)
Total gr 100g 50g
Method:

1.Cetostearyl alcohol is melted using a water bath.

2.Liquid paraffin is added to the melt and then heated to 60OC, which gives an oily mixture.
3.Cetrimide is dissolved in the purified water and warmed to 60OC to form its aqueous
solution.

4.Aqueous solution id added to oily mixture with continuous stirring. Stirring is carried out
until the cream becomes cold.

5.It is transferred in a suitable container, labeled and dispensed.

Directions for use: Apply on the affected area as directed by the physician.

ii. Prepare and dispense dimethicone cream BPC

Ingredients Official amount Amount used

Dimethicone 350
Cetrimide
Cetostearyl alcohol
Liquid paraffin
chlorocresol
Total 100g 50g

Method:

1. Cetostearyl alcohol is melted in the liquid paraffin and silicone fluid. This oily
phase is cooled to 60oC.
2. The chlorocresol and cetrimide is dissolved in water. This aqueous solution is
warmed to 60oC.
3. The aqueous solution is added to the oily phase. It is mixed with an electronic
stirrer until it becomes cold.
Precaution: Cationic creams should not be applied on inflamed or abraded skin and near the
eyes.

Directions for use: Applied as directed by the physician or pharmacist.

c.Non-ionic creams

Non-ionic creams are prepared by fusion method. The creams are prepared using one or more
combinations of the following non-ionic emulsifying agents such as highe fatty alcohols,
macrogol ester polysorbates, polyvinyl alcohol and self-emulsifying monostearin.

Examples:

1. Prepare and dispense 50g of cetomacrogol cream BP.

Ingredients Official amount Amount used
Cetomacrogol 30g 15g
Emulsifying ointment
Benzyl alcohol 1.5g 0.75g
Propyl hydroxyl benzoate 0.08g 0.04g
Methyl hydroxyl benzoate 0.15g 0.075g
Purified water 68.27g 34.135g
 Total 100g 50g

Method:

1.Cetomacrogol emulsifying ointment is melted and its temperature is maintained at 60OC.

2.Propyl hydroxyl benzoate, Methyl hydroxyl benzoate and benzyl alcohol are dissolved in
purified water.

3.This aqueous solution is heated and maintained at a temperature of about 60OC.

4.Then the aqueous solution is added to the oily solution with continuous stirring until the
preparation becomes cold.

5.The cream is transferred to a suitable container, labeled and dispensed.

Direction for use: The cream is used as instructed.

2.Prepare and dispense 50g of hydrocortisone cream BPC.

Ingredients Official amount Amount used

Hydrocortisone acetate 1g 0.5g
Cetomacrogol 30g 15g
Emulsifying ointment
Chlorocresol 0.1g 0.05g
Purified water 68.9g 34.45g
Total 100g 50g
Method:

1.Chlorocresol is dissolved in purified water by heating.

2.Cetomacrogol emulsifying ointment is melted using a water bath.

3.Chlorocresol solution is added to the above melted cetomacrogol emulsifying ointment.

4.Continuous stirring is carried out until the preparation becomes cold.

5.Finally, hydrocortisone acetate is added to the preparation.

6.The cream is transferred in to a suitable container, labeled and dispensed.

Directions for use:The cream is used as instructed.

2 Oily creams / water in oil creams

These creams are composed of small droplets of water dispersed in a continuous oily phase.
These creams are difficult to handle when compared to aqueous creams.

Advantages:

1.Hydrophilic drugs when incorporated into oily creams are released more readily from them
when compared to aqueous creams.

2.Oily creams are more moisturizing than aqueous creams as they provide an oily barrier,
which reduce water loss from the stratum corneum.

3.The oily creams are greasy in nature.

Depending upon the type of emulsifying agent used, oily creams are classified into two
types:a.Sterol Creams,b.Soap Creams

a. Sterol Creams: In sterol creams, the emulsifying agent used is either wool fat or wool fat
or wool alcohol.

Examples
1. Prepare and dispense 50 g of proflavine cream BPC.
Ingredients Official amount Amount used
Proflavine hemisulphate 0.1 g 0.05g
Chlorocresol 0.1g 0.05g
Yellow bees wax 2.5g 1.25g
Wool fat 5.0g 2.5g
Water (bailed and cooled) 25.0g 12.5g
Liquid paraffin 67.3g 33.5g
Total 100g 50g
Method:

1.In a covered china dish, chlorocresol is dissolved in 75% of liquid paraffin by gentle
heating.

2.Yellow bees wax and wool and wool fat are melted by heating at 70OC.

3.To the above melted mixture, chlorocresol solution is added.

4.Proflavine hemisulphate is dissolved in water by heating at 70OC.

5.Aqueous solution is added to the oily solution with continuous stirring.

6.The rest of the liquid paraffin is warmed and added to the above preparation with
continuous stirring until the cream is cooled.

7.The cream is transferred into a suitable container, labeled and dispensed.

Directions for use: The cream is used as instructed.

b.soap creams: In the preparation of soap creams, the emulsifying agents used are calcium
soap, triethanolamine soap etc. some emulsions are made without using heat like emulsion
containing soaps of liquid fatty acids.

Soap creams are of two types:

1.Borax creams

2.Triethanolamine creams

Borax creams:

The creams containing borax soaps as emulgents are called borax creams. These creams are
water in oil type but are not stable.

Example:cold cream

Ingredients Official amount

White bees wax 20g
Liquid paraffin 60g
Borax 1g
Water 19g
Total 100g
Method:

1.Melt bees wax in liquid paraffin at 70oC.

2.Dissolve borax in water, heat the solution to 70oC.

3.Gradually, add the borax solution to he wax mixture, simultaneously, stir the cream until it
sets.

4.Avoid excessive stirring to prevent entrapment of air in the preparation.

1.Triethanolamine creams

These creams contain Triethanolamine soaps as the emulgents. The soaps formed between
Triethanolamine and Fatty acids like oleic acid, stearic acid etc., are called Triethanolamine
soaps and their HLB value is 12.

Example: Barrier cream

Ingredients Official amount

Hard paraffin 25g
Soft paraffin 11.75g
Liquid paraffin 3.5g
Cetostearyl alcohol 5g
Triethanolamine 0.7g
Stearic acid 1.8g
Chlorocresol 0.2g
 Water( bailed and cooled) 52.05g
Total 100g
Method:

1.Cetostearyl alcohol, hard paraffin, stearic acid and soft paraffin are melted together.

2.To the meltesdmixture liquid paraffin is added and heated 70oC.

3.Triethanolamine is dissolved in chlorocresol and heated to 70oC.

4.The aqueous solution is added to oily solution with continuous stirring until the preparation
becomes cold.

FORMULATION OF CREAMS

The following are the active ingredients used in the formulation of creams.

1.Penetration enhances

They increase the penetration property of drugs thereby increases the rate and extent of
percutaneous absorption of drugs.

Example: solvents like decylmethyl sulfoxide, surfactants like sodium laurel sulphate and
miscellaneous chemicals like N, N- diethyl– m– toluadine and urea.

2.Oils are oleaginous substances

Vegetable oils such as almond oil, olive oil, peanut oil and sesame oil which are mixtures of
unsaturated and saturated fatty acids constitute the oily phase of the creams.

3.Emulgents or emulsifiers

A.Acyl lactates

These are the compounds resulting from chemical bonding between fatty acids and lactic
acid. They are mild and non-irritant to the skin and eyes. They give emollient feeling to
the skin. They are suitable for oil-in-water or water-in-oil Emulsion systems, sodium salts of
acyl lactates are used.

Example: sodium stearyl -2-lactlate.

b.Non- ionic surfactants:

They are compatible with many drugs and are used in both oil-in-water and water-in-oil
emulsions. They are compatible with strong acidic salts or strong electrolytes.

3. PASTES

►Pastes are semisolid preparations meant for external application to the skin. ►They
generally contain large amount of finely powdered solids such as starch, zinc oxide, calcium
carbonate etc.
►They provide a protective coating over the areas to which they are applied.

►The base may be anhydrous (liquid or soft paraffin) or water-soluble (glycerol or a

mucilage).

►Their stiffness makes them useful as protective coatings.

e.g. magnesium sulfate paste., zinc and coal tar paste

Differences between pastes and ointments;

(i) Pastes generally contains a large amount (50%) of finely powdered solids. So they are
often stiffer than ointments.

(ii) When applied to the skin pastes adhere well, forming a thick coating protects and soothes
inflamed and raw surfaces and minimizes the damage done by scratching in itchy conditions
such as chronic eczema. it is comparatively easy to confine pastes to the diseased areas
whereas ointments, which are usually less viscous, tend to spread on to healthy skin, and this
may result in sensitivity reactions if the preparations contain a powerful medicament such
as dithranol.

(iii) Because of the powder contents pastes are porous; hence, perspiration can escape. Since
the powders absorbs exudate, pastes with hydrocarbon base are less macerating than
ointments with a similar base.

(iv)They are less greasy than ointments but since their efficacy depends on maintaining a
thick surface layer they are far from attractive cosmetically.

(v)Most of the pastes are unsuitable for treating scalp conditions because they are difficult to
remove from the hair.

Classification of pastes

Based on the type of bases used in the formulation, pastes may be classified as follows:

Pastes

Fatty pastes aqueous gel pastes hydrocolloid pastes

Eg: zinc oxide paste, eg: corboxy methyl Eg: dental paste, Lassar’s paste.
Cellulose sodium paste, unna’s paste.

Magnesium sulphate paste,

 Resorcinol sulphur paste.

Fatty pastes:

1.The formulation of the fatty paste makes use of fatty bases or oleaginous bases. Eg: zinc
oxide paste, Lassar’s paste.

1.Aqueous gel pastes:

Aqueous gel pastes make use of water miscible bases.

eg: corboxy methyl Cellulose sodium paste, Magnesium sulphate paste, Resorcinol sulphur
paste.

2.Hydrocolloid pastes:The formulation of hydrocolloid pastes makes use of hydrocolloid

bases.

Eg: dental paste, unna’s paste, etc.

Zinc oxide gelatin paste or Unna’s paste.

It is used for its astringent, protective and antiseptic action. The gelatin swells in water and
provides good gelation property to the paste. The resultant paste thus formed possesses good
absorptive properties. The formula for unna’s paste is given below.

formula Qty for 50g

Zinc oxide 7.5g
Gelatin 7.5g
Glycerine 17.5g
water To make 50g

FORMULATIONS OF PASTES

The various types of bases used in the preparation of are as follows:

1. Hydrocarbon base:

Soft paraffin and liquid paraffin are commonly used bases for the preparation of paste.

Name of the preparation Active ingredients Base Use

1.Compound Zinc Paste B.P. Zinc oxide Soft paraffin Eczema, psoriasis.

2.Compound Zinc & Salicylic acid Zinc oxide Soft paraffin Eczema, psoriasis.
Paste B.P.(Lassar’s Paste) &Salicylic acid

Coal tar
Soft paraffin Eczema
3. Coal tar paste Dithranol
Ring worm or
4. Dithranol paste compound Soft paraffin psoriasis

Aluminium oxide

5. Aluminium paste B.P.C. Liquid paraffin Protectant

(Baltimore Paste)

2. Water miscible base:

Name of the preparation Base Use

1.Resorcinol & sulfur Paste B.P.C. Emulsifying ointment Dandruff and are easily removable
from the hair.

2.Zinc & Coal tar Paste Emulsifying wax

Eczema
3.Magnesium sulfate paste Magnesium sulfate -
B.P.C.(Morison’s paste) 45% Used to treat boils, because of their
powerful osmotic effect of the salt and
the glycerol.
4. Titanium dioxide paste Phenol in glycerol Absorbs exudates from weeping skin
B.P.C.
Suspension of TiO2, conditions.
ZnO, light kaolin and
red Fe2O3 in glycerol +
water.

3. Water soluble bases

Water soluble bases are prepared from mixtures of high and low molecular weight
polyethylene glycols (or macrogols).

Name of the preparation Base Use

1.Water soluble dental pastes Neomycin sulfate Sterilizing infected root

canal

2.Triamcinolone Dental paste Triamcinolone acetonide

B.P.C. Anti-inflammatory
in an adhesive paste

(NaCMC, pectin + gelatin)

METHODS OF PREPARATION:

Like ointment, pastes are prepared by trituration and fusion methods. Trituration method is
used when the base is liquid or semisolid.

Fusion method is used when the base is semisolid or solid in nature.

Preparation 1.

Name: Compound Zinc Paste

Formula Zinc oxide, finely sifted 25 g

Starch, finely sifted 25 g

White soft paraffin 50 g

Type of preparation: Paste with semi-solid base prepared by fusion and trituration.

Procedure;

(a)Zinc oxide and starch powder are passed through No. 180 sieve.

(b)Soft paraffin is melted on a water bath.

(c)The required amount of powder is taken in a warm mortar, triturated with little melted base
until smooth. Gradually rest of the base is added and mixed until cold.

Preparation 2.

Name: Zinc and Coal tar Paste B.P.C.

Formula: Zinc oxide, finely sifted

Coal tar

Emulsifying wax

Starch

Yellow soft paraffin.

Type of preparation: Paste with semi-solid base prepared by fusion.

Procedure

Method-I

(a)Emulsifying wax is melted in a tared dish (700C).

(b)The coal tar is weighed in the dish. Stirred to mix.

Soft paraffin is melted in a separate dish (700C) and about half is added to the tar-wax
mixture; stirred well. Remainder is added; stirred again until homogeneous.

Allowed to cool at about (300C) and zinc oxide (previously passed through 180 mesh) and
starch, in small amount with constant stirring. Stirred until cold.

Method-II

Wax and paraffin melted together, mixed well and stirred until just setting. Powders are
mixed on a slightly warm tile and the tar is incorporated. This method eliminates the risk of
overheating.

EVALUTIONS OF PASTES

Pastes should be evaluated in order to ensure that they meet the established standards and
requirements. They are evaluated for the following properties.

1. Heat Stability

The evaluation of heat stability for pastes is carried out in order to ensure the stability of the
formulation at varying temperatures. The samples in tubes are kept at different temperatures
and conditions of humidity and the response of the pastes at varying temperatures is noted.

2. Viscosity of the Product

The viscosity of the product is determined in order to ensure the effective flow property.It can
done by Instrument called Viscometer.

3. Compatability with container

The evaluation studies for the compatibility of the product with container have to be carried
out in order to ensure the stability of the formulation with the container chosen for marketing
the product.The container shall not impart any chemical toxicity to the final formulation.

4. Safety of the Product

The final formulation must be evaluated for safety before the product is ready for
consumption.This may involve knowledgeable selection of the new material with regard to
their physiological properties and compatibility with other ingredients.

5. Sensitization of Paste

This test is carried out in order to determine the sensitivity of the product towards the skin
which would be lead to any hypersensitivity reaction. The method is known as repeated patch
testing method.It involves repeated application of the product on group of subjects at regular
intervals of time.The final results are evaluated on the sensitive skin of subjects in order to
determine the sensitivity.
6. Particle size

Particle size determination studies are necessary in order to assist the flow properties of the
finished formula.It can be determined either by microscopic methods or rheological
techniques.The determination of particle size may also helps to determine the sensitivity.

7.Gelation Behaviour of Paste

The gelation behavior of pastes may assist in their flow and spreadability.

Storage of pastes

Semisolid preparations(Pastes) are mostly susceptible to microbial contamination as they

consist of water and volatile matter.Threfore,they should be stored in a tightly closed
container in cool and dry place free from contamination.

4. JELLIES(GELS)

Jellies are transparent or translucent, non-greasy, semisolid preparation generally applied

externally.

They are used for medication, lubrication and some miscellaneous applications.

Types of jellies: Mainly three types as fallows.

1.Medicated jellies

(i) Water soluble drugs like local anaesthetics, spermicides and antiseptics are suitable for
incorporation in the jellies.

(ii) They are easy to apply and evaporation of the water content produces a pleasant cooling
effect. The medicinal film usually adheres well and gives protection but is easily removed by
washing when the treatment is complete.

e.g. ephedrine sulfate jelly - used to arrest bleeding from nose.

Pramoxine HCl,local Anesthetics - relieves discomfort of Pruritis and haemorrhoids.

Phenyl mercuric nitrate - As spermicidal contraceptive.

2.Lubricant jelly

Catheters, items of eletrodiagnostic equipment, such as cystoscopes and rubber gloves or

finger stalls used for rectal and other examinations require lubrication before use.

The lubricants must be sterile for articles inserted into sterile regions of the body, such as
urinary bladder.

For painful investigations a local anaesthetic may be included as in Lignocaine Gel B.P.C.

3. Miscellaneous jellies
For miscellaneous purpose.The following are more specialized jellies -

(a) Patch testing

Here the jelly is the vehicle for allergens applied to the skin to detect sensitivity. Several
allergens may be applied on one person. The viscosity of the jelly and it leaves on drying help
to keep the particles separate.

(b) Electrocardiography

To reduce electrical resistance between the patients skin and electrodes of the cardiograph, an
electrode jelly may be applied. This contains Nacl to provide good conductivity and often
pumice powder which, when applied onto the skin, removes part of the horny layer of the
epidermis, the main layer of electrical resistance.

FORMULATION

Pharmaceutical jellies are usually prepared by adding a thickening agent such as tragacanth
or carboxy methylcellulose (CMC) to an aqueous solution in which drug has been dissolved.

The mass is triturated in a mortar until a uniform product is obtained.

For the preparation of jellies whole gum is preferred rather than powdered gum because the
former gives a clear preparation of uniform consistency.

The following gelling agents are used for the preparation of jellies.

(i) Tragacanth

The main hydrophilic component of tragacanth that gels in water has been named bassorin -
hence, tragacanth jellies are sometimes called bassorin paste.

The amount of gum required for a preparation varies with its use:

(a)For lubricating jelly 2 to 3%.

(b)For dermatological vehicles about 5%.

(c)For incorporation of ichthamol, resorcinol, salicylic acid and other medicaments, about 5%
is generally used. All formulations contain alcohol and glycerol or a volatile oil to disperse
the gum and prevent lumpiness when water is added.

(d)They vary in viscosity, due to the natural origin of the gum and variations in milling and
storage.

(e) The film left on the skin tends to flake.

(f)Viscosity is rapidly lost outside the pH range of 4.5 to 7.0; for example if benzoic acid is
used as the preservative.

(g)They are susceptible to microbial growth.

Example:

Formula Ichthamol 1.0 g

Tragacanth 2.5 g

Alcohol 90% 5.0 g

Glycerin 1.0 g

Purified water q.s. 50.0g

Procedure

(i)Alcohol is taken in a 100 ml, wide mouthed jar and then tragacanth is added to it. (The
reverse order may lead to lump formation). Mixed well.

(ii)Water is added as quickly as possible and mixed.

(iii) Separately ichthamol, glycerin and 10 ml water is mixed. Final weight is adjusted by
adding more of water.

2. Sodium alginate

Uses: As lubricant - 1.5 to 2 % is used.

As dermatological vehicle - 5 to 10 % is used.

A trace of Ca - salt (CaCl2) may be added to increase the viscosity and most formulations
contain glycerol as a dispersing agent.

Advantage

Sodium alginate has an advantage over tragacanth that is available in several grade or
standardized viscosity.

3. Pectin

●Pectin is a very good gelling agent and is used in the preparation of many types of jellies
including edible jellies.

●Glycerin is used as a dispersing agent and humectant in dermatological jellies.

●Jellies must be packed in well-closed containers because they lose water rapidly by
evaporation and this lose water rapidly by evaporation and this is increased by the
susceptibility of pectin gels to syneresis (i.e. exudation of the aqueous phase as a result of
contraction of the gel).

4. Starch

Starch in combination with gelatin and glycerin is commonly used for preparations of jellies.
Glycerin in 50% may act as preservative.

Medicaments are incorporated in the cold jelly by trituration.

5. Gelatin

Insoluble in cold water but swell and softens in it. It is soluble in hot water.

Hot solution contains 2% gelatin forms a jelly on cooling.

Very stiff (15%) jellies are melted before used and after cooling to desired temperature are
applied with a brush to the affected area. The area is covered with bandage and the dressing
may be left in place for several weeks.

Zinc-gelatin jelly (Unna’s paste) is such an example.

Formula: Zinc oxide 15g

Gelatin 15g

Glycerin 35g

Water 35g

Procedure

(i)Gelatin soaked in water until softened.

(ii)Glycerin is added and heated over bath until the glycerin is dissolved.

(iii) Adjust the weight to 85g if necessary by adding more amount of water.

(iv)ZnO is passed through sieve (#120). Required amount is added in small amounts to the
molten base with gentle stirring. Stirring is continued until a viscous product is obtained.

(v)The product so obtained is poured in a tray to a depth of about 1cm with continuous
trituration throughout the operation. When the mass is set, carefully the mass is cut into
pieces of about 1.5cm2 with a blade or sharp knife.

6. Cellulose and other derivative

Methyl cellulose and sodium carboxy methyl cellulose

1. Produce neutral jellies of stable viscosity.

2. Have good resistance against microbial growth.

3. Clear due to freedom from insoluble impurities.

4. Produce strong film after drying on the skin.

Use: Sodium carboxy methyl cellulose can be used to prepare lubricating jellies and sterile
jellies.

e.g. lignocine gel - because it can withstand autoclaving temperature.

►Other cellulose derivatives are:

Hydroxy propyl methyl cellulose (Hypermellose)

Carbomer

Polyvinyl alcohols.

7. Clays

Gels containing 7 to 20 % of bentonite can be used as dermatological bases.

Disadvantages

1. They are opalescent and lack attractiveness.

2. Their pH is about 9.0 i.e. not suitable for application on the skin.

3. Residue on the skin is powdery and rather silky.

Evaluation of Jellies

Evaluation Parameters

Jellies cannot be evaluated based on a single property such as viscosity as they exhibit non-
Newtonian rheological behavior.The various evaluation parameters involved in the
assessment of the properties of the gellies are be as follows:

1.Yield Value

It is a measure of the force required to extrude the material from the deformable bottle tube.It
can be determined by the use of an instrument called the penetrometer.The penetrometer
consists of a metal needle that pierces through the system and the distance of penetration of
the needle is measured from which the yield value may be calculated.

2. Spreadability

The spreadability test is performed to determine the extent of spreadability of jellies based on
their rheological properties.
3. Stability

This test is known as the shipping test and performed to determined the extent of jellies at
varying temperature, which the product may experience while exporting to other countries.
4. Safety

The safety of the product on use should determined in order to check the effect of the product
by evaluating the physiological properties of the raw materials.

Preservation of jellies

Although some bases like clays and cellulose derivative(s) resist microbial contamination but
since all the jellies contain large amount of water, therefore must be suitably preserved.

e.g. Methyl paraben 0.1 to 0.2 % is commonly used.

Loss of water can quickly lead to skin formation on jellies and to prevent the hygroscopic
substances, e.g. glycerol, propylene glycol or sorbitol solution may be added.

Bases and medicaments sensitive to heavy metals are sometimes protected by a chelating
agent e.g. ethylene diamine tetra acetic acid (EDTA)

5. POULTICE

Poultice are paste-like preparations used externally to reduce inflammation because they
retain heat well. After heating, the preparation is spread thickly on a dressing and applied, as
hot as the patient can bear it, to the affected area.

Uses

(i)Glycerol, because of its hygroscopic nature, is believed to draw infected materials from the
tissues when the poultice is used for boils and similar infections.

(ii)Methyl salicylate (an antirheumatic drug), thymol (a powerful bactericide), boric acid (a
weak antimicrobial agent), and peppermint oil (which contributes to the smell) are used for
different purposes.

Method of applying the poultice

(i)For use, the poultice is heated, with occasional stirring, until it can only be tolerated on
the back of the hand.

(ii)Then it is spread thickly on lint or other dressing and applied to the affected area which is
sometimes first covered with muslin to facilitate removal after use.

(iii)A thick layer of cotton wool is applied to retain the heat and a covering of oiled silk may
be added to protect clothing.

Example

The only example given in the pharmacopoeia is Kaolin Poultice B.P.C.

Formula: Heavy kaolin, finely sifted and dried at 1000C 52.7 g

Boric acid, finely sifted 4.5 g

 Ethyl salicylate 0.2 ml

Thymol 50 mg

Peppermint oil 0.05 ml

Glycerin 42.5 g

Procedure

(a)Kaolin is spread in a suitable quantity of kaolin in a thin layer, e.g. on a tray of aluminium
foil, and dried at 1000C until the weight is constant. Allowed to cool down and then passed
through No. 180 sieve.

(b)Boric acid and kaolin are mixed in a mortar. Gradually the mixed powder is triturated with
glycerol to form a smooth paste.

(c)The paste is transferred to a heat-resistant glass-jar, protected either wit a paper or

aluminium foil and heated at 1200C for 1 hour in a hot-air oven, with occasional stirring. The
antimicrobial effects of the heat and glycerol destroy the sporing pathogens that may be in the
kaolin. (Above 1200C glycerin may degrade).

(d)After cooling a mixture of thymol, methyl salicylate and peppermint oil are mixed.
(Eutectic mixture).

(e)Kaolin poultice is stored in well closed containers to prevent loss of volatile ingredients
and absorption of moisture from the atmosphere by glycerin.

6. PLASTERS AND GLYCEROGELATINS

Plasters:Plasters are semisolid masses containing either paper plastic or fabric backing and
meant to be applied on to the skin to provide prolonged contact of drug with the skin. They
are of two types as follows:

1. Un-medicated plasters
2. Medicated plasters.
1.Un-medicated plasters:

These are also called sticking plasters or adhesive bandages. These are small dressings meant
for minor injuries. They are usually covered by woven fabric, plastic or latex rubber. They
provide protection or mechanical support at the site of application. They have an absorbent
pad for covering the wounds and the fabric adheres to the skin surrounding the wounds.
Therefore, these plasters help to hold the dressing in place and prevent dirt from entering the
wound.e.g: adhesive plaster.

2.Medicated plasters:

These plasters consist of drugs incorporated into resin, wool fat or beeswax. They should be
heated gently before application to make them spreadable. They consist of three parts.
a.Base sheet: it has an upper surface made up of an adhesive layer. The adhesive layer has
provision skin contact.

b.Medicated layer: it consists of the drug and is present above the adhesive layer.

c.Isolating layer: it is a water-proof layer that isolates the adhesive layer.

Glycerogelatins:Glycerogelatins are basically semisolid masses whose composition includes

15% gelatin, 40% glycerin, 35% water and may or may not contain the active medicament.
Their general method of preparation involves the following steps:

a.Heating the gelatin along with water bath in order to soften and dissolve it.

b.The next step involves the addition of glycerin with or without the drug.

c.The mixture so obtained is allowed to cool and is constantly stirred until the mixture gets
congealed. Basically, there are two types of glycerogelatins.

1.Medicated glycerogelatins:These glycerogelatins comprises of active medicaments andare

used to treat dermatological conditions.

They are softened by applying heat before use and then applied on the skin surface with a
brush. The glycerogelatin tends to become hard upon application, over which a bandage is
placed and left untouched for several weeks.

Examples Concentration of glycerine Concentration of drug

Iodoform glycerogelatin 15% 10%
(antiseptic)
Salicylic acid glycerogelatin 35% 10%
(keratolytic)
Firm zins glycerogelatin 25% 10% zinc oxide
(ulcer protective)
Soft zinc glycerogelatin 35% 10% zinc oxide
(astringent and protective)