DESIGN OF DOSAGE FORMS

- Pharmaceutics
o The process of converting a drug into a medicine
o It is the stages that follow the discovery or synthesis or
the drug, its isolation and purification, and testing for
advantageous pharmacological effects and absence of
serious toxicological problems
o Used in pharmacy and pharmaceutical science to
encompass many subject areas that are all associated with
the steps to which a drug is subjected towards the end of
its development
o Medicines
 Drug delivery systems
 They are means of administering drugs to the body
in a safe efficient, reproducible and convenient
manner

- Review of common terminologies in dosage forms

Term Definition
Aerosols Suspension of fine solid or liquid particles in gas;
a substance dispensed from a pressurized
container; includes the container and process
used to dispense the aerosol
Cachets A solid composed of dry powdered active and/or
inert ingredient(s) covered by an edible shell.
The shell consists of two concave pieces of wafer
made of flour and water
Capsules A small soluble container, usually made of
gelatin, that encloses a dose of an oral medicine
or a vitamin
Collodions Liquid preparation intended for local application
having as their base a solution of pyroxylin in a
mixture of ether and alcohol
Creams Emulsions of oil and water containing a
substance and used externally for a variety of
cosmetic or medicinal purposes
Dentrifices A preparation for cleansing and polishing the
teeth; it may contain a therapeutic agent, such
as fluoride, to inhibit dental caries
Dental liniments These are liquid preparation which are apllied to
the gum for its local stimulant and anesthetic
effects
Douche An aqueous solution which is used to clean the
body cavities
Dusting powders A powder used on the skin, especially to relieve
irritation or absorb moisture; A fine powder,
such as talcum powder, used on the skin
Elixers A sweetened aromatic solution of alcohol and
water, serving as a vehicle for medicine
Emulsions Heterogeneous system of two immiscible liquid
where one is dispersed in the droplet form
throughout the body of the other liquid. The
liquid which is in the droplet form is called
dispersed phase, discontinuous or internal
phase. The other liquid in which the first liquid
is dispersed is called dispersion medium,
continuous or  external phase
Enemas A solution introduced into the rectum to promote

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 evacuation of feces or as a means of introducing
nutrients, medicinal substances, or opaque
material for radiologic examination of the lower
intestinal tract
Ear drops A topical, liquid form of medication for the local
treatment of various conditions of the ear, such
as inflammation or infection of the lining of the
external auditory canal or impacted cerumen
(earwax)
Eye drops A medicated solution for the eyes that is applied
in drops
Gargles Aqueous solutions use for treating pharynx &
naso-pharynx by forcing air from the lungs
through the gargle which is held in the throat
Gels Commonly the term gels refer to any product of
gelatinous consistency whether it is hydrated
inorganic chemical or a colloidal solution
Granules Agglomerates of powdered materials prepared
into larger, free flowing particles
Glycerides Solutions or mixture of various substance in not
less than 50% by weight of glycerin
Honeys Thick liquid preparations containing honey as a
base
Implants A medical device manufactured to replace a
missing biological structure, support a damaged
biological structure, or enhance an existing
biological structure
Inhalants Solutions which are to be inhaled by the patients
Injection A preparation intended for parenteral
administration or for consulting or diluting a
parenteral article prior to administration
Insufflations These are medicated powders designed to be
blown into the ear, nose, throat or body cavities
by means of a device known as an insufflator.
Bulk insufflation has largely disappeared and
has been replaced by individual doses of
powdered drugs supplied in hard capsules and
inhaled from a device which breaks the capsule
and allows the patient to inhale the powder. This
type of insufflation is used mainly for drug
delivery into the respiratory tract by inhalation
Jellies Transparent or translucent, non-greasy,
semisolid preparation mainly used externally
Juices Expressed, strained, liquid obtained from fresh
ripe fruits of certain plants
Linctuses Linctuses are viscous, liquid oral preparations
that are usually prescribed for the relief of
cough. They usually contain a high proportion of
syrup and glycerol which have a demulcent
effect on the membranes of the throat. The dose
volume is small (5ml) and, to prolong the
demulcent action, they should be taken
undiluted
Liniments Solution or mixtures of various substances in oil
or alcoholic solutions of soap or emulsion
intended for external application
Lotions These are fluid preparations for external
application without friction. They are either
dabbed on the skin or applied on a suitable
dressing and covered with a waterproof dressing
to reduce evaporation

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Lozenge A small, medicated candy to be dissolved slowly
into the mouth for localized effects upon the
mouth or throat; a troche
Magmas Liquid preparations containing sufficient
suspended insoluble substances usually
inorganic to make a product quite viscous
Mixtures A liquid preparation intended for oral
administration in which drug(s) is (are)
dissolved, suspended or dispersed in a suitable
vehicle and generally several dose are contained
in a bottle
Mouthwashes These are similar to gargles but are used for oral
hygiene and to treat infections of the mouth
Mucilages Thick, viscid, adhesive liquid prepared by
dispersing gum in water or by extracting with
water the mucilaginous principles from
vegetable substances.
Nasal drops and Drugs in solution may be instilled into the nose
sprays from a dropper or from a plastic squeeze bottle.
The drug may have a local effect, e.g.
antihistamine, vasoconstrictor, decongestant.
Alternatively the drug may be absorbed through
the nasal mucosa to exert a systemic effect, e.g.
the peptide hormones oxytocin and vasopressin
Ocuserts Ocular inserts or ophthalmic inserts are sterile
preparations, with a thin, multilayered, drug-
impregnated, solid or semisolid consistency
devices placed into conjunctival sac and whose
size and shape are especially designed for
ophthalmic application
Ointments Soft semisolid preparations meant for external
application to the skin or mucous membrane
Oleovitamins Solution of vitamins in oil and commonly we  are
using oil soluble vitamins (A & D) .
Opthalmic Solutions of medicaments in an aqueous medium
solutions used in the eye as eye drops or eye washes (eye
lotions)
Parenterals These are sterile dosage forms containing one or
more medicaments and designed for parenteral
administration
Paints Liquids for application to the skin or mucous
membranes. Skin paints often have a volatile
solvent that evaporates quickly to leave a dry
resinous film of medicament. Throat paints are
more viscous due to a high content of glycerol,
designed to prolong contact of the medicament
with the affected site
Pastes Semisolid preparations for external application
that differ from similar products in containing a
high proportion of finely powdered medicaments
Pessaries Solid dosage forms containing one or more
active drug and are intended for vaginal
insertion
Pills Oral dosage forms which consist of spherical
masses prepared from one or more medicaments
incorporated with inert excipients. Pills are now
rarely used. The term pill is used colloquially
(yet incorrectly) as a synonym for oral
contraceptive tablets which are actually
prepared by compression.
Plasters A semi-solid composed of a soft, smooth mass

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 with relatively thick consistency and strong
adhesiveness that becomes solid when dry
Poultices A semi-solid composed of a soft, moist mass that
is made by wetting an absorbent solid substance
Powders The pharmaceutical powder are the mixture of
drugs or chemical with or without the addition of
other substances as dry powder
Snuffs These are finely divided solid dosage forms of
medicament inhaled into nostrils for its
antiseptics, bronchiodilator and decongestion
action
Solutions Liquid preparations that contain one or more
chemical substance dissolved in a suitable
solvent or mixture of mutually miscible solvents.
Spirits Alcoholic or hydrochloric solutions of volatile
substances
Spray Aqueous or oily solutions of medicinal agents,
sprayed or drop in nose or throat
Suspensions Liquid preparations containing insoluble
substances whether it is already in suspension
form or in powder form to make suspension by
addition of liquid.
Suppositories Solid dosage forms intended for insertion into
the body offices where they melt, soften or
dissolve and exert local or systemic effects
Syrups Syrups are concentrated solutions of a sugar
such as sucrose in water or in other aqueous
liquid
Tablets Tablet are solid pharmaceutical unit dosage
form of  Medicines containing one or more
medicinal agents with or without diluents
prepared by moulding the mixture in the form of
a fine powder or by compressing it in the form of
granular powder  into a suitable shape by mean
of dies
Tinctures An alcoholic or hydroalcoholic solution prepared
from vegetable materials or chemical substances
Toothache drops These are preparations for temporary relief of
toothache
Washes Usually pleasantly flavored solutions and often
are colored

- Pre-formulation
o A consideration of the steps that need to be performed
before formulation proper can begin
o Involves a full understanding of the physicochemical
properties of drug molecules and excipients and how they
interact in dosage forms

- Three major considerations in the design of dosage forms

o Drug factors
 The physicochemical properties of the drug
o Biopharmaceutical considerations
 Factors affecting the absorption of the drug
substance from different administration routes
 Such as how the administration route of a dosage
form affects the rate and extent of drug absorption
into the body
o Therapeutic considerations

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  The disease state to be treated, which in turn decide
the most suitable type of dosage form, possible
routes of administration and the most suitable
duration of action and dose frequency for the drug
in question
 Includes consideration of the clinical indication to be
treated and patient factors

Principles of Dosage Forms

- The principal objective of a dosage form design is to achieve a

predictable therapeutic response to a drug included in a
formulation which is capable of large-scale manufacture with
reproducible product quality

- Numerous features of a medication to ensure product quality

o Physical stability
o Chemical stability
o Suitable preservation against microbial contamination
o Uniformity of dose of drug
o Acceptability to users, including both prescriber and
patient
o Suitable packaging and labeling

- Bioavailability optimization includes the following factors

o Solubility requirements
o Drug particle size and physical form
o Consider appropriate additives and manufacturing aids
coupled to selecting the most appropriate administration
route(s) and dosage form(s)
o Suitable manufacturing processes and packaging

- Dosage forms available for different administration routes

Administration Dosage forms

route
Solutions
Syrups
Suspensions
Emulsions
Oral Gels
Powders
Granules
Capsules
Tablets
Suppositories
Ointments
Rectal Creams
Powders
Solutions
Ointments
Creams
Pastes
Lotions
Topical
Gels
Solutions
Topical aerosols
Transdermal patches
Parenteral Injections (solution,
suspension, emulsion forms)

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 Inhalations
Sprays
Gases
Solutions
Nasal
Inhalations
Solutions
Eye Ointments
Creams
Solutions
Suspensions
Ear
Ointments
Creams

- Broad classification of dosage forms as per their physical nature

- Classification of dosage forms depending on sterility

Biopharmaceutical Aspects of Dosage Form Design

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- Two general ways of drug absorption
o Passive diffusion
 Thought to control the absorption of most drugs
 Driven by the concentration gradient existing across
the cellular barrier, with drug molecules passing
from regions of high to low concentration
 Lipid solubility and degree of ionization of the drug
at the absorbing site influence the rate of diffusion
o Specialized transport mechanisms
 Active transport
 Facilitated transport

- Routes of dug administration

o Variation in time of onset of action for different dosage
forms

Time of onset of Dosage forms

action
Seconds Intravenous injections
Intramuscular injections
Subcutaneous injections
Minutes Buccal tablets
Aerosols
Gases
Short-term depot injections
Solutions
Suspensions
Powders
Minutes to hours
Granules
Capsules
Tablets
Modified-release tablets
Several hours Enteric-coated formulations
Depot injections
Days to weeks
Implants
Varies Topical preparations

o Oral route
 Most frequently used route for drug administration
 Simplest, most convenient and safest means of drug
administration
 Usually intended for systemic effect resulting from
drug absorption through the various epithelia and
mucosa of the gastrointestinal tract (GIT). A few
drugs, however intended to dissolve in the mouth for
rapid absorption or for local effect in the tract due to
poor absorption by this route of low aqueous
solubility
 Disadvantage
 The onset of action is relatively slow
 Possibilities of irregular absorption and
destruction of certain drugs by enzymes and
secretions of GIT
o Example is insulin-containing
preparations are inactivated by the
action of stomach fluids
 Tablets
 Disintegrants
o Promote tablet break-up into granules
and powder particles in the GIT,

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 facilitating drug dissolution and
absorption
 Purposes of tablet coating
o Provide a protective barrier to
environment factors for drug stability
purposes or to mask unpleasant drug
taste, as well as to protect drugs from
the acid conditions of the stomach
o Enteric coating
 Achieved by the use of polymeric-
based tablet cores or coating
membranes
 Controlled release
o Also called modified release
o The following are controlled release
 Fast-dissolving systems
 Controlled
 Delayed
 Sustained-release formulations
o Benefits
 Reduced frequency of drug-related
side-effects and monitoring
maintaining steady drug-plasma
levels for extended periods
 Important when medications are
delivered for chronic conditions or
where constant levels are required
to achieve optional efficacy, like
the following
 Angina
 Hypertension
 Capsules
 Solid dosage forms containing drug and
usually appropriate filler(s), enclosed in a hard
and soft shell composed of gelatin
 Drugs are released from capsules faster than
from tablets
 Renewed interest in filling semi-solid are
microemulsion formulations into hard gelatin
capsules has been used to provide rapidly
dispensing dosage forms for poorly soluble
drugs
 Uniformity of dose can be readily achieved and
various sizes, shapes and colors of shell are
commercially available
 Suspensions
 Useful means of administering large amounts
of drugs that would be inconvenient if taken in
a tablet or capsule form
 Useful for patients who experience difficulty in
swallowing tablets and capsules
 Useful for pediatric patients
o Rectal route
 Suppositories
 Solid forms intended for introduction into body
cavities (usually rectal but also vaginal and
urethral) where they melt releasing the drug
 Drugs administered rectally enter the systemic
circulation without passing through the liver,
an advantage for drugs significantly

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 inactivated by the liver following oral route of
absorption
 This route of administration is also indicated
for drugs inactivated by the gastrointestinal
fluids when given orally or when the oral route
is precluded, as for example when a patient is
vomiting or unconscious
 Disadvantage is that this route is inconvenient
and drug absorption is often irregular and
difficult to predict
o Parenteral route
 A drug administered parenterally is one injected via
a hollow needle into the body fluids at various sites
and to varying depths
 Three main parenteral routes
 Subcuraneous (sc)
 Intramuscular (im)
 Intravenous (iv)
 Other routes
 Intracardiac
 Intrathecal
 Preferred when rapid absorption is essential, as in
emergency situations or when patients are
unconscious and unable to accept oral medication
and in cases when drugs are destroyed, inactivated
or poorly absorbed following oral administration
 In general, blood levels attained are more
predictable than those achieved by oral dosage
forms
 Depot preparations can be achieved by
subcutaneous implants or pellets, which are
compacted or molded discs of drug placed in loose
subcutaneous tissue under the outer layers of the
skin
 Needle free injection systems and devices has been
used recently which propel drug in aqueous solution
or powder form at high velocity directly through the
external layers of the skin
o Topical
 Involves percutaneous absorption that is often poor
and erratic
 Applied to the skin mainly for local action but can
also be used for systemic drug delivery
 Some examples of drug classes that uses this dosage
forms
 Antiseptics
 Antifungals
 Anti-inflammatory
 Some important features of topical preparations
 Opthalmic
o Required among other features to be
sterile
 Nasal
o Solutions or suspensions delivered by
drops or fine aerosol from a spray
 Otic
o Viscous to prolong contact with affected
area
o Respiratory

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  Provide an excellent surface for absorption when the
drug is delivered in gaseous, aerosol mist or
ultrafine solid particle form
 Particle size largely determines the extent to which
the drug penetrate the alveolar region
 Drug particles that are in the region 0.5 to 1 um
diameter reach the alveolar sacs
 Particles smaller are exhaled
 Particles larger are deposited upon larger
bronchial airways
 Useful for the direct treatment of asthmatic
problems, using both powder aerosol (ex. sodium
cromoglycate) are metered aerosols containing the
drug in liquefied inert propellant ( ex. salbutamol
sulfate aerosol)
 Increasingly recognized as a useful means of
administering the therapeutic agents emerging from
biotechnology requiring systemic distribution and
targeted delivery such as peptides and proteins

Drug Factors in Dosage Form Design

- Particle-size and surface area

o Reduction in particle size results in increase in the
specific surface of powders
o The following are dependent on particle size
 Drug dissolution rate
 Dependent to varying degrees of particle size,
size distribution and interactions of solid
surfaces
 Absorption rate
 Dosage form content uniformity
 Stability
o Poorly aqueous soluble drugs showing a dissolution rate
limiting step in the absorption process will be more
readily bioavailable when administered in a finely
subdivided form with large surface than as a coarse
material

- Solubility
o All drugs, regardless of their administration route, must
exhibit at least limited aqueous solubility for therapeutic
efficiency
o Solubilities of acidic or basic compounds are pH
dependent and can be altered by forming salts, with
different salts exhibiting different equilibrium solubilities

- Dissolution
o The process by which the drug particles dissolve
o For a drug to be absorbed it must first be dissolved in the
fluid at the site of absorption
o The dissolution of a drug is described in a simplified
manner by the Noyes-Whitney equation (physical
pharmacy ☺)

- Partition coefficient and pKa

o For relatively insoluble components the dissolution rate is
often the rate determining step in the overall absorption
process

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 o For soluble compounds the rate of permeation across
biological membranes is the rate determining step
o pH-partition theory for drug absorption
 Henderson-Hasselbalch equation
 For calculating the proportions of ionized and
unionized specie at a particular pH

- Crystal properties
o Practically all drug substances are handled in powder
form at some stage during manufacture into dosage forms
o Polymorphism
 Drug substances can exist in more than one form
with different molecular packing arrangements in
the crystal lattice
o Crystal engineering
 Provide new particles with required properties

- Stability
o Chemical stability in formulation
o Packaging is important in stability
o Drug substances decompose as a result of the effects of
the following
 Heat
 Oxygen
 Light
 Moisture
o Drug classification according to their sensitivity to
breakdown
 Stable in all conditions (ex. Kaolin)
 Stable if handled correctly (ex. Aspirin)
 Only moderately stable even with special handling
(ex. Vitamins)
 Very unstable (ex. certain antibiotics in solution
form)
o Buffer
 May be required to control the pH of the
preparation to improve stability
o Preservatives
 Required in liquid dosage forms which are sensitive
to microbial attack

- Organoleptic
o Modern medicines require that pharmaceutical dosage
forms are acceptable to the patient
o Flavors
 Its use applies primarily to liquid dosage forms
intended for oral administration
 Available as concentrated extracts, solutions,
absorbed onto powders or microencapsulated
 Flavors are usually composed of mixtures of internal
and synthetic
 Bitter, sweet, salty or acid element of flavor are
quickly recognized by the taste buds in the tongue
 Sucrose
 Used as sweetening agent
 Alternative is sodium saccahrin which is 200-
700 times sweeter depending on concentration
 Sorbitol
 Recommended for diabetic patients
o Colors

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  Employed to standardize or improve on existing
drug color, to mask a color change or complement a
favor
 Natural sources or color
 Carotenoids
 Synthetic sources of color
 Amaranth
 Dyes may be aqueous (ex. amaranth) or oil soluble
(ex. sudan IV) or insoluble in both (ex. aluminum
lakes)

- Other drug properties

o Hygroscopicity
o Flowability
o Compactability

Therapeutic Considerations in Dosage Form Design

- Systemic or local? Duration of action? Used in emergency

situations?

- A single drug substance is prepared into a number of dosage

forms to satisfy both the particular preferences of the patient or
physician and the specific needs of a certain clinical situation

- May asthmatic patients use inhalation aerosols, from which the

drug is rapidly absorbed into the systemic circulation following
deep inhalation for raid emergency relief and oral products for
chronic therapy

- Patient requiring urgent relief from angina pectoris, a coronary

circulatory problem, place tablets of nitroglycerin sublingually
for rapid drug absorption directly into the blood capillaries

- Age of the patient also plays a role in defining the type of

dosage forms made available

- New drug containing formulations which deliver drugs to

specific targets” in the body
o Liposomes
o Nanoparticles

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