PHARMACEUTICAL

CHAPTER=1
DOSAGE FORMS

DRUG: “A drug may be defined as an agent, intended for use in the

diagnosis, mitigation, treatment, cure or prevention of disease in man or in
animals”.

DOSAGE FORM: Drugs are rarely administered in their original pure

state. They are converted into suitable formulation which are called dosage
forms. Every dosage form is a combination of the drug and other non-drug
components.

CLASSIFICATION OF DOSAGE FORMS

DOSAGE FORM

Site of Use
Application
Physical Route of
state administration

(i) Solid (i) Oral (i) Skin (i) Internal

(ii) Semisolid (ii) Parenteral (ii) Eye (ii) External
(iii) Liquid (iii) Rectal (iii) Tooth
(iv) Gaseous (iv) Nasal (iv) Hand
(v) Foot
(vi) Hair
(vii) Nose

Route of Dosage
administration forms
Oral Powders, tablets, capsules, solutions,
emulsions, syrups, elixirs, magmas, gels,
cachets, pills.
Parenteral Solutions, suspensions, emulsions.
Transdermal Ointments, creams, powders, pastes,
lotions, plaster
Rectal Suppositories, tablets, ointments, creams,
douches, foams.
Urethral Suppositories
Sublingual Lozenges, tablets
Intranasal Solutions, sprays, inhalations.
Conjunctival Ointments
Intra-ocular Solutions
Intra-respiratory Aerosols

CACHETS
Cachets consists of a dry powder enclosed in a shell. The shell is prepared
from a mixture of rice flour and water by moulding into suitable shape
and then dried.
Two types of cachets are there:
(i) Wet seal cachets:
Lower half of the cachet is filled with powdered drug. Then the flange of
the empty upper half of the cachet is moistened with water, and pressed
over the lower half. The cachet is dried for 15 minutes.
(ii) Dry seal cachets:
Drug powder is filled in the lower half and the upper half is pressed over
it just like a capsule.
Use:
They are used for administering the drug with unpleasant taste and a large
dose. Before administration, a cachet should be immersed in water for few
seconds and then placed on the tongue and swallowed with water.
e.g. - Sodium aminosalicylate cachets, Sodium aminosalicylate and
isoniazid cachets.

CAPSULES
Capsule are the solid unit dosage form of medicament in which the drug
or drugs are enclosed in a practically tasteless, hard or soft soluble
container of shell made up of gelatin.

Hard gelatin capsules are made up of two cylindrical halves, one slightly
larger in diameter but shorter in length known as cap and the other
slightly shorter in diameter but longer in length known as base.

Soft gelatin capsules are flexible in nature. They may be spherical, ovoid
cylindrical or tubes. The small spherical capsules are also known as
‘pearls’. Soft gelatin capsules are used to enclose solids, semisolids or
liquids for oral administration the capsule is placed on the tongue and
swallowed with a drink of water. Examples of hard gelatin capsules:
Ampicillin capsules, multivitamin capsules.
Examples of soft gelatin capsules: chloramphenicol soft gelatin capsules.

DUSTING POWDER
These are meant for external application on to the skin and are generally
applied in a very fine state of subdivision to avoid local irritation.
Dusting powders are of two types:
(i) Medical
(ii) Surgical
Medical dusting powders are mainly used for superficial skin conditions
and for antiseptics, anti- pruritic, astringent, anti-perspirant, absorbent,
protective and lubricant purposes.
E.g. dicophane dusting powder, zinc and salicylic acid dusting powder

Surgical dusting powders are used in body cavities, and also on major
wounds as a result of burns and umbilical cords of infants. Surgical
dusting powders must be sterilised before their use.
Dusting powders are generally prepared by mixing two or more
ingredients on of which must be either starch, kaolin or talc as one of the
ingredients of the formulations. Talc and kaolin are commonly used
because they are chemically inert. however, since these materials are
usually contaminated with pathogenic bacteria, these must be sterilised.
e.g. Neosporin powder

LOZENGES
Lozenges are solid dosage form of medicaments which are meant for slow
dissolution in the mouth. Along with medicament they contain a
sweetening agent, flavoring agent and a strong binding agent. They may
be prepared either by moulding or by compression.
Examples are compound bismuth lozenges, liquor ice lozenges.

PESSARIES
Pessaries are solid unit dosage form of medicament meant for
introduction into vagina. The bases used for the manufacture of pessaries
are such that at room temperature they retain the original shape but when
inserted into the body cavity either it melts or dissolve in the cavity fluids
to release the medicament.

POWDERS
Powders are solid dosage form of medicament meant for internal and
external use. The powders meant for internal use are known as oral
powders whereas those meant for external use are known as dusting
powders.

TABLETS
Tablets are unit solid dosage form of medicament or medicament with or
without suitable diluents. They are prepared usually by compression.
Tablets are generally meant for oral administration but may be used by
other routes of administration.
E.g.-paracetamol tablets.

SUPPOSITORIES
Suppositories are special shaped solid dosage form of medicament for
insertion into body cavities other than mouth. These products are so
formulated that after insertion, they will either melt of dissolve in the
cavity fluids to release the medicament.
Suppositories vary in shapes, sizes and weights. General suppositories
from 1 to 2 gm are prepared with either cocoa-butter or glycerol- gelatin
base.
E.g. aminophylline.

SEMISOLID DOSAGE FORMS

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.
e.g. cetomacrogol cream, cetrimide cream.

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 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 very quickly.

Disadvantages:
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 acidification of oils take place.

They are used for lubricating catheters, surgical gloves and rectal
thermometers.
The gelling agents may be gelatin, or a carbohydrate such as starch,
tragacanth, sodium alginate or cellulose derivative.

OINTMENTS
Ointments are the soft semisolid, greasy preparations meant for external
application onto the skin or mucous membrane (rectum and nasal
mucosa).They usually contain a medicament dissolved, suspended or
emulsified in the base. Ointments are used for their emollient and
protective action to the skin. E.g.-compound benzoic acid ointment,
certified emulsifying ointment

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 make them useful as protective coatings. E.g.-
magnesium sulfate paste.
OPHTHALMIC OINTMENTS
Ophthalmic ointments are meant for application to the eye. They should
be sterile and free from irritation. They should be packed in sterile
containers which should keep the preparation sterile until whole of it is
used up. E.g.-atropine eye ointment Chloromycetin eye ointments

LIQUIDS
AROMATIC WATERS: Aromatic waters are also known as medicated
waters. They are dilute, usually saturated, aqueous solutions of volatile oils
(e.g. peppermint oil, cinnamon oil) or volatile substances (e.g. camphor).
Uses:
(i) Some of them have a mild therapeutic action but
(ii) Mainly they are used as flavoring agents in preparations meant for
internal use.

SYRUPS: Syrups are liquid oral preparations in which the vehicle is a

concentrated aqueous solution of sucrose or other sugar.

Advantages of syrups
1. Syrups retards oxidation because it is partly hydrolyzed into reducing
sugar such as dextrose and laevulose.
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.

ELIXIRS: Elixirs are clear, liquid, oral preparations of potent or nauseous

drugs. They are pleasantly flavored and usually attractively colored and are
very stable. They are used for the production of clear solution. Essential
oils from flavoring agents may produce faint opalescence, hence alcohol
10 20% is useful for keeping oils in solution.

LINCTUSES: Linctus’s 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. Linctus’s 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.
 CHAPTER=2
Metrology

Metrology is the branch of science dedicated to measurement, which is

defined as the process of comparing an unknown quantity.

There are two type of weight and measurement system used in pharmacy.

1. Imperial system
2. Metric system
Imperial system: It is an old system based on arbitrary units. This system are
used to required dispensing the prescriptions.

Imperial system is divided into two parts:

a. Avoirdupois system
b. Apothecaries system
a. Avoirdupois system: In this system Pound is the standard unit for the
measurement of mass and weight.
b. Apothecaries system: The standard weight in this system is grain and all
are weight are derived from it.

Metric system: This system of weight and measurement is a new system. It

is also known as international system of weight and measurement

Isotonic Solution

An isotonic solution is one that has the same osmolarity, or solute

concentration, as another solution. If these two solutions are separated by
a semipermeable membrane, water will flow in equal parts out of each
solution and into the other. The effect is zero water flow between the two
solutions, although water is moving both ways. In biology, some cells must
be maintained in an isotonic solution to support cellular functions. Many
animal cells, which lack a cell wall to provide support against the effects of
water pressure, rely on the stability of the external environment to maintain
their shape. Most animals maintain the pH and osmolarity of the fluids
inside of their bodies to create isotonic solutions to bathe their cells in. This
solution can carry nutrients and water, but only in proportions equal to that
inside the cell.

A depiction of a cell in an isotonic solution can be seen above. Note that

because there is the same concentration of solute molecules inside and
outside of the cell that water molecules are simply exchanged through
the cell membrane. This can be contrasted to the effects of a hypertonic
solution, in which water molecules leave the cell, or a hypotonic solution in
which water enters the cell.

Examples of Isotonic Solution: Blood Cells

When the plasma surrounding blood cells is an isotonic solution, compared

to the solution inside the blood cells, the cells function normally. The
isotonic solution allow the cells to move water and nutrients in and out of
the cells. This is necessary for blood cells to perform their function of
delivering oxygen and other nutrients to other parts of the body. If the cells
are in a hypertonic environment, they will become plasmolyzed and will not
contain enough water to perform cellular functions. If the cells exist in
a hypotonic environment, they will lyse, spilling their contents into the
bloodstream. This can cause dangerous side effects, as well as the loss of
many blood cells.
Indian Pharmacopoeia:
The Indian Pharmacopoeia Commission (IPC) is an Autonomous Body
under Ministry of Health & Family Welfare, Govt, of India primarily with
the objectives of regularly updating the Indian Pharmacopoeia by publishing
new edition and its addenda, National Formulary of India and other related
tasks such as preparing, certification and distribution of reference substances
& functions as National Coordination Centre (NCC) for Pharmacovigilance
Programme of India (PvPI).
 CHAPTER=3
Packaging of Pharmaceuticals

A Pharmaceutical Package container is an article or device which contains

the Pharmaceutical Product and the container may or may not in direct
contact with the product. The container which is designed for
pharmaceutical purpose must be stable.

Ideal Qualities of a Pharmaceutical Package.

1. It should have sufficient mechanical strength so as to withstand handling,
filling, closing and transportation.
2. It should not react with the contents stored in it.
3. It should be of such shape that can be elegant and also the contents can be
easily drawn from it.
4. It should not leach alkali in the contents.
5. The container should not support mould growth.
6. The container must bear the heat when it is to be sterilized.
7. The contents of container should not be absorbed by the container.
8. The material used for making the container should be neutral or inert.
9. Any part of the container or closure should not react with each other.
10. Closure should be of non toxic nature and chemically stable with
container contents.

Types of Package
1. Primary Packaging: Primary packaging are those package which are in
direct contact with the Pharmaceutical formulation. The main aim of
primary package is to protect the formulation from environmental, chemical,
mechanical and/or other hazards.

2. Secondary Packaging: The package external to Primary package is known

as secondary package. This package provide additional protection during
warehousing and also provide information about drug product for e.g
Leaflets.

Functions:
 Protect the flexible containers.
 Protection from tough handling during transportation.
3. Tertiary packaging Examples: Barrel, crate, container, pallets, slip sheet.
It is outer package of secondary packaging & prevents damage to the
products. It is used for bulk handling & shipping.

Components of packaging
1. Container: The containers refer in which the product/ medicine is placed
& enclosed. It is direct contact with drug.
2. Closure: It is tightly packs the container to exclude oxygen, carbon
dioxide, moisture & prevents the loss of water and volatile substances from
the products.
3. Carton/outer: Which gives secondary protecion against mechanical and
other environmental hazards. It is outer covering. Cartoons are made up of
cardboard, wood pulp etc.
4. Box: In this multiples of products are packed. It provides primary defense
against external hazards. The boxes are made up of thick cardboard and
wood.
The materials selected for packaging must have the following
characteristics:
 Mechanical properties.
 Physico-chemical properties
 Biological properties.
 Economical aspects.

Types of packaging materials: The following materials are used for the
consruction of containers and closures.
1. Glass a. Type-1 borocilicate glass.
2. Type -2 treated sodalime glass.
3. Type-3 regular sodalime glass.
4. Type-4 NP general purpose sodalime glass.

METALS
Advantages
a. Metal containers are strong, relatively unbreakable opaque.
b. Resistance to chemical attack.
c. Impervious to water vapor, bacteria
d. Readily coats a number of metals

Disadvantages
a. This is the most expensive metal among tin, lead, aluminium, & iron.
b. Currently some eye ointments still package in pure tin ointment tubes.

Aluminum
Advantages
1. Aluminium is a light metal hence the shipment cost of the product is less.
2. They provide attractiveness of tin at somewhat lower cost.

Disadvantages
a. As a result of corrosion process H2 may evolve
b. Any substance that react with the oxide coating can cause corrosion.

Uses: Aluminum ointment tubes, Screw capes.

Plastics
General properties of plastics:
 Robust, strong, light, aesthetic.
 Plastics are synthetic polymers of high molecular weight.
 Easy to handle.
 They are poor conductor of heat.

Types of plastics: Plastics are classified in to 2 groups according to their

behavior when heated.
 Thermoplastic type: On heating, they soften to a viscous fluids which
hardens again on cooling. Eg: Polyetyline, Polypropylene, PVC,
Polystyrene, Nylon etc.
 Thermosetting type: When heated, they may become flexible but they do
not become liquid, usually hard and brittle at room temperature. Eg: Phenol,
Formaldehyde, Urea etc.

Rubber: Natural rubber consists of long chain polymers of isoprene units

linked together in the cis portion. Its most important source is the tree Hevea
braziliensis from which latex, containing 30 to 40% of rubber in colloidal
suspension, exudes when shallow cuts are made in the bark. A. Butyl rubber:
These are co polymer of isobutylene with 1-3% of butadiene.
Advantages
 Permeability to water vapor and air is very low.
 Water absorption is very low.
 CHAPTER= 4
Size Separation
Size separation is a unit operation that involves the separation of a mixture of various size particles into two or
more portions by means of screening surfaces. Size separation is also known as sieving, sifting, screening. This
technique is based on physical differences b/w the particles such as size, shape and density.

Factors affecting size reduction

 Material structure.
 Some substances are homogeneous in character.
 Mineral substances may have lines of weakness.
 The materials splits to form flake-like particles.
 Vegetable drugs have a cellular structure often leading to long fibrous particles.

Size Separation Methods:

a. Sieving
b. Cyclone separator
c. Air separator Elutriation.

Sieving:
Sieving Working of mechanical sieves A. Agitation Oscillation: Back and froth Vibration: Rapid vibration
Gyration: Rotatory B. Brushing: C. Centrifugal: Principle: Sieving

a. Sieves:
Sieves Sieves for pharmacopeial testing are constructed from wire cloth with sqare meshes, woven from wires
of brass, bronze, stainless steel etc., Number of sieve: No of meshes in a length of 2.54 cm in each transfer
direction parallel to the wires. Nominal size of aperture: Distance between the wires. Length of the side of the
square aperture. (in mm or µm). Nominal diameter of the wire: Made of suitable diameter in order to give a
suitable aperture and sufficient length. Approximate % sieving area: The area of the meshes as a percentage of
the total area of the sieve. Generally the sieving area is kept within the range of 35-40% in order to give
suitable strength to the sieve. Tolerance average aperture size: Fine sieves cannot be woven with same
accuracy.

b. Cyclone Separator:
Principle: Centrifugal force used to separate the solids from fluids Depends not only on particle size but particle
density Hence, coarse particles will settle down and fine particles will be carried out with fluid .

Working: The suspension of particles is introduced tangentially at a very high velocity. The rotatory flow
causes the particles to be acted on by centrifugal force. The solids (Coarse) are thrown out the walls, thereafter
it falls in to a conical base and discharged through solid outlet Cylindrical Vessel with a conical base

Uses: It is used to separate the suspension of solids from liquids or gases

c. Air Separator:
Principle: It works on the same principal as that of cyclone separator, but in this case the air movement is
obtained by means of rotating disc and blades
Working: The powder is passed to fall on rotating discs and blades. Rotating discs will produce air flow and
rotating blades will reduce the size of the particles Cylindrical Vessel with a conical base

Uses: It is attached to ball mill or hammer mill to separate and return oversized particles for further size
reduction.

Elutriation Methods:
Elutriation Methods the size separation of powders is based on the low density of fine particles and high density
of coarse particles. Elutriation tank is used to separate the coarse and fine particles after levigation . The dry
powder or paste made from levigation process is mixed with large quantity of water and made suspend in the
tank. Depending on density of particles they will settle down or suspended in water. The sample is drawn from
different heights through outlets and dried. Thus the powder with various size fractions are obtained.

Advantages: The process is continuous The separation is quick as compare to that other methods of separation.
Depending on the number of fractions required, the same number of tubes of different area of cross section can
be connected nowadays in elutriation process, the particles are suspended in a moving fluid. The apparatus
consists of vertical columns. One column will give single separation in two fractions. For further fractions the
number of tubes of increasing area of cross section is connected in series. The fractions are separated and dried.
Application of size separation:
Application/uses of size separation Determination of particle size & size distribution used for production of
tablet and capsule. It is a quality control tool for analysis of raw material. To optimize the process condition
such as method of agitation, time of screening, feed rate etc. To measure the efficiency of size reduction
equipments.
 CHAPTER=5
Mixing

Mixing may be defined as the process in which two or more than two components in a separate or roughly
mixed condition are treated in such a way so that each particle of any one ingredient lies as nearly as possible to
the adjacent particles of other ingredients or components. This process may involve the mixing of gases, liquids
or solids in any possible combination and in any possible ratio of two or more components. Mixing of a gas
with another gas, mixing of miscible low viscosity liquids and mixing of a highly soluble solid with a low
viscosity liquid to effect dissolution are relatively simple as compared to the mixing of gases with liquids,
mixing of liquids of high viscosity though miscible, mixing of two immiscible liquids such as aqueous and oily
solutions to form emulsions, mixing of solids with liquids when the proportion of solids is high and mixing of
solids with solids, specialized equipments are required for these operations.
Some of the examples of large scale mixing practiced in pharmacy are:
 Mixing of powders in varying proportions prior to granulation or tableting.
 Dry mixing of the materials for direct compression in tablets.
 Dry blending of powders in capsules and compound powders (insufflations).
 Blending of powders in cosmetics in the preparation of face powders, tooth powders
 Dissolution of soluble solids in viscous liquids for dispensing in soft capsules and in the preparation of
syrups
 Mixing of two immiscible liquids for preparation of emulsions.

Objectives of mixing
 To ensure that there is uniformity of composition between the mixed ingredients which may be
determined by taking samples from the bulk material and analyzing them, which should represent
overall composition of the mixture.
 To initiate or to enhance the physical or chemical reactions e.g. diffusion, dissolution etc.
 When two or more than two miscible liquids are mixed together, this results in to a solution known as
true solution.
 When two immiscible liquids are mixed in the presence of an emulsifying agent, an emulsion is
produced.
 When a solid is dissolved in a vehicle, a solution is obtained.
 When an insoluble solid is mixed with a vehicle, a suspension is obtained.
 When a solid or liquid is mixed with a semisolid base, an ointment or a suppository is produced.
 When two or more than two solid substances are mixed together, a powder is obtained which when
filled into capsule shell is known as capsules and when compressed under heavy pressure is called
tablet.

Types of Mixtures: Mixtures may be classified as follows:

1. Positive mixtures
2. Negative mixtures
3. Neutral mixtures
I. Positive Mixtures – These types of mixtures are formed when two or more than two gases or miscible liquids
are mixed together by means of diffusion process. In this case no energy is required provided the time allowed
for solution formation is sufficient. These types of materials do not create any problem in mixing.
II. Negative Mixtures – These types of mixtures are formed when insoluble solids are mixed with a vehicle to
form a suspension or when two immiscible liquids are mixed to form an emulsion. These mixtures are more
difficult to prepare and require a higher degree of mixing with external force as there is tendency of the
components of these mixtures separate out unless they are continuously stirred.
III. Neutral Mixtures – Many pharmaceutical products such as pastes, ointments and mixed powders are the
examples of neutral mixtures. They are static in their behavior. The components of such products do not have
any tendency to mix spontaneously but once mixed, they do not separate out easily.

Factors influencing mixing

™ Nature of the product – Rough surface of one of the components does not induce proper mixing. The reason
for this is that the active substance may enter into the pores of the other ingredient. A substance that can adsorb
on the surface can decrease aggregation, for e.g. addition of colloidal silica to a strongly aggregating zinc oxide
can make it a fine dusting powder which can be easily mixed.
™ Particle size – Variation in particle size leads to separation as the small particles move downward through
the spaces between the bigger particles. As the particle size increases, flow properties also increases due to the
influence of gravitational force on the size. It is easier to mix two powders having approximately the same
particle size.
™ Particle shape – For uniform mixing, the particles should be spherical in shape. The irregular shapes can
become inter-locked and there are less chances of separation of particles once these are mixed together.
™ Particle charge – Some particles exert attractive forces due to electrostatic charges on them. This results to
separation or segregation.

Mechanism of Mixing In all type of mixers, mixing is achieved by applying one or more of the following
mechanisms:
Convective mixing – During convective mixing transfer of groups of particles in bulk take place from one part
of powder bed to another. Convective mixing is referred to as macromixing.
Shear mixing – During shear mixing, shear forces are created within the mass of the material by using agitator
arm or a blast of air.
Diffusive mixing – During this mixing, the materials are tilted so that the gravitational forces cause the upper
layers to slip and diffusion of individual particles take place over newly developed surfaces. Diffusion is also
sometimes referred to as micromixing.

Powder mixers Dry mixer (stationary container):

For batch work the dry mixer which is the stationary shell type is often used. This consists of a semi-cylindrical
trough, usually covered and provided with two or more ribbon spirals. One spiral is right-handed and the other
left-handed. So that the material is worked back and forth in the trough. Ribbon cross section and pitch and
number of spirals on the ribbon are varied for different materials varying from low density, finely divided
materials to fibrous or sticky materials. It may be centre discharge or end discharge. Another variation is the
mounting of cutting blades on the central shaft.

A broad ribbon lifts and conveys the materials while a narrow one will cut through the materials while
conveying. Ribbon blenders are often used on the large scale and may be adapted for continuous mixing.

Dry Mixer: The paddle mixer has a stationary outer vessel and the powders are agitated by paddles rotating
within. The equipment is suitable to heating, by jacketing the vessel, and also permits a kneading effect by the
use of appropriately shaped paddles or beaters. In the bowl mixer the paddle is mounted vertically and in the
trough mixer (e.g., dry mixer) a number of vanes are mounted horizontally. Vertical screw mixer: In these types
of mixers, the screw rotates about its own axis while orbiting around the centre axis of the conical tank. In
another variation, the screw does not orbit but remains in the centre of the conical tank and is tapered so that the
swept area steadily increases with increasing height. This type of mixer is mainly used for free flowing solids.
 CHAPTER=6
Evaporation
Evaporation means simply vaporization from the surface of the liquid. Evaporation is an unit operation by
which a solvent is evaporated from a solution by boiling the liquor in a suitable vessel and withdrawing the
vapor, leaving a concentrated liquid residue.

Objective of evaporation:
To make a solution more concentrated. Generally extracts are concentrated in this way.

Factors affecting evaporation:

(i) Temperature:
Heat is necessary to provide the latent heat of vaporization, and in general, the rate of evaporation is
controlled by the rate of heat transfer. Rate of heat transfer depends on the temperature gradient.
Many pharmaceutical agents are thermolabile. So the temperature that will cause the least possible
decomposition should be used.
E.g. many glycosides and alkaloids are decomposed at temperature below 100 0C.
E.g. Hormones, enzymes and antibiotics are extremely heat sensitive substances. E.g. Malt extract
(containing enzyme) is prepared by evaporation under reduced pressure to avoid loss of enzymes.
Some antibiotics are concentrated by freeze-drying.
(ii) Temperature and time of evaporation
Exposure to a relatively high temperature for a short period of time may be less destructive of active
principles than a lower temperature with exposure for a longer period.
Film evaporators used a fairly high temperature but the time of exposure is
very short. An evaporating pan involve prolonged heating.
(iii) Temperature and moisture content
Some drug constituents decompose more rapidly in the presence of moisture, especially at a raised
temperature (by hydrolysis). Hence, evaporation should be carried out at a low controlled
temperature, although the final drying can be performed at higher temperature when little moisture
remains.
E.g. Belladonna Dry Extract is an example of this type.
(iv) Type of product required
Evaporating pans or stills will produce liquid or dry products, but film evaporators will yield only
liquid products. So a dilute extract can be first concentrated in a film evaporator and then the
concentrated extract may be died in an evaporating pan.
(v) Effect of concentration
As the liquor becomes concentrated, the increasing proportion of solids results in elevation of the
boiling point of the solution. This leads to a greater risk of damage to thermo labile constituents and
reduction of the temperature gradient.
In general concentrated solutions will have increased viscosity, causing thicker boundary layers, and
may deposit solids that may build up on the heating surface that reduce heat transfer.
All these problems may be minimized by turbulent flow condition.

EVAPORATORS
Evaporators are classified according to the form of the movement,
(i) Natural circulation evaporators.
(ii) Forced circulation evaporation
(iii) Film evaporators

(I)Natural Circulation Evaporator

Construction
The apparatus consists of a hemispherical, or shallow pan, constructed from a suitable material such as
copper or stainless steel and surrounded by a steam jacket. The hemispherical shape gives the best surface/
volume ratio for heating, and the largest area for separation of vapor. The pan may have a mounting,
permitting it to be tilted to remove the product, but the shallow form makes this arrangement somewhat
unstable, and an outlet at the bottom, is common.
 EVAPORATING PAN

Working
The dilute solution is taken in the pan. Steam is introduced through the steam inlet into the jacket to heat
the pan. In these evaporators the movement of the liquid results from convection currents set up by the
heating process. The concentrated liquid is collected through the outlet placed at the bottom of the pan.

Advantages:
(a) It is simple and cheap to construct.
(b) It is easy to use, clean and maintain.

Disadvantages:
(a) Having only natural circulation, the overall coefficient of heat transfer will be poor and solids are likely to deposit
on the surface, leading to decomposition of the product and a further deterioration in heat transfer.
(b) Also many products give rise to foaming.
(c) The total liquor is heated over all the time, which may be unsatisfactory with thermo labile materials.
(d) The heating surface is limited and decreases proportionally as the size of the pan increases.
(e) The pan is open, so the vapor passes to the atmosphere, which can lead to saturation of the atmosphere.
(f) Only aqueous liquids can be evaporated in these pans.
(g) Pan evaporation cannot be done under reduced pressure.
(h) Can only be used for thermo labile products.

EVAPORATING STILLS
Construction
It consists of a jacketed-
evaporating pan with a
cylindrical cover that connects it
to a condenser. The overall
assembly is called still. The
cover is clamped with the
evaporating pan. Working
The dilute liquid is fed into the
still, the cover is clamped. Steam
is introduced into the jacket. The
liquid is evaporated and
condensed in the condenser and
collected. The product (i.e.
concentrated liquid) is collected
through the product outlet.

Advantages:
(a) Simple construction and easy to
clean and maintain.
(b) The vapor is removed by
condensation which
(i) speeds evaporation
(ii) reduces inconvenience and
(iii) Allows the equipment to be used for solvents other than water e.g. ethanol.
 (c) A receiver and vacuum pump can be fitted to the condenser, permitting operation under reduced pressure and,
hence, at lower temperature.

Disadvantages:
(a) Natural convection only
(b) All the liquor is heated all the time
(c) The heating surface is limited.

SHORT TUBE EVAPORATOR (Basket type vertical short tube evaporator)

Construction and Principle
Construction
The evaporator is a cylindrical vessel. The lower portion of the vessel consists of a nest of tubes with the
liquor inside and steam outside– this assembly is called calendar. The specifications of calendric are as
follows:
Tube length: 1–2m
Tube diameter: 40 – 80
mm Diameter of evaporator:2.5 m
Number of tubes: 1000
The feed inlet is at the top of the calendar. The
product outlet is placed at the bottom of the
evaporator. Steam inlet and outlet is placed from
the side of the calendric. Working
 The feed is introduced through the feed inlet and
the liquor is maintained at a level slightly above the
top of the tubes (of calendar), the space above this
is left for the disengagement of vapor from the
boiling liquor.
 The liquor in the tubes is heated by the steam and
begins to boil, when the mixture of liquid and vapor
will shoot up the tubes (in a similar manner to that
of a liquid that is allowed to boil to vigorously in a
test-tube).
 This sets up a circulation, with boiling liquor rising
up the smaller tubes of the calendric and returning
down the larger central down take.
 The product is collected through the product outlet.
Advantages
1. Use of tubular calendric increases the heating area,
Possibly by a factor of 10 to 15 compared to that of an external jacket.
2. The vigorous circulation reduces boundary layers and keeps solids in suspension, so increasing the rate of heat
transfer.
3. Condenser and receiver can be attached to run the evaporation under vacuum with no aqueous solvents.
Disadvantages
1. Since the evaporator is filled to a point above the level of the calendric, a considerable amount of liquid is heated
for a long time. The effect of this continual heating can be reduced to some extent by removing concentrated liquor
slowly from the outlet at the bottom of the vessel.
2. Complicated design, difficult for cleaning and maintenance.
3. The head (pressure) of the liquor increases pressure at the bottom of the vessel and, in large evaporators where the
liquor depth may be of the order of 2 m; this may give rise to a pressure of about 0.25 bar, leading to elevation of
the boiling point by 5 to 60C.
FORCED CIRCULATION EVAPORATORS
Forced circulation evaporators are
natural circulation evaporators with
some added form of mechanical
agitation. Different forms of forced
circulation evaporators can be designed.
 An evaporating pan, in which the
contents are agitated by a stirring rod or
pole could be described as a forced
circulation evaporator.
 A mechanically operated propeller or
paddle agitator can be introduced into an
evaporating pan or still.
 Propeller or paddle agitator can be
introduced into the down take of a short-
tube evaporator.
 A typical forced circulation evaporator
can be shown as follows:

Construction
The evaporator consists of a short tube
calendric and a large cylindrical vessel
(body of the evaporator) for separation
of vapor and
Liquid takes place. The liquor inlet is provided at the side of the cylindrical vessel. A pump is fitted in
between the calendric and the body of the evaporator. A tangential inlet for liquid under high pressure is
placed at neck of the body of the evaporator. The vapor outlet is placed at the top of the body and it may be
passed through a condenser to collect the condensed liquid.
Working Principle
Feed is introduced through the liquor inlet. Pump will force the liquid through the calendric. Steam heats
the liquid inside the calendric. As it is under pressure in the tubes the boiling point is elevated and no
boiling takes place. As the liquor leaves the tubes and enters the body of the evaporator through the
tangential inlet there is a drop in pressure and vapor flashes off from the superheated liquor. The
concentrated liquid is pumped out through the product outlet and the vapor is collected through the vapor
outlet.
Advantages
 Rapid liquid movement improves heat transfer, especially with viscous liquids or materials that deposit solids or
foam readily.
 The forced circulation overcomes the effect of greater viscosity of liquids when evaporated under reduced
pressure.
 Rapid evaporation rate makes this method suitable for thermo labile materials, e.g. it is used in practice for the
concentration of insulin and liver extracts.

FILM EVAPORATORS
Film evaporators spread the material as a film
over the heated surface, and the vapor escapes
the film.

Long tube evaporators (Climbing

film evaporators)
Construction and working principle
The heating unit consists of steam-jacketed
tubes, having a length to diameter ratio of
about 140 to 1, so that a large evaporator may
have tubes 50 mm in diameter and about 7 m
in length.
The liquor to be evaporated is introduced into the bottom of the tube, a film of liquid forms on the walls
and rises up the tubes, hence it is called climbing film evaporator. At the upper end, the mixture of vapor
and concentrated liquor enters a separator, the vapor passes to a condenser, and the concentrated liquid to
a receiver.Cold or pre heated liquor is introduced into the tube. Heat is transferred to the liquor from the walls
and boiling begins, increasing in vigor. Ultimately sufficient vapor has been formed for the smaller bubbles to
unite to a large bubble, filling the width of the tube and trapping a ‘slug’ of liquid above the bubble .
As more vapor is formed, the slug of liquid is blown up the tube, the tube is filled with vapor, while the liquid
continues to vaporize rapidly, the vapor escaping up the tube and, because of friction between the vapors and
liquid, the film also is dragged up the tube up to a distance of 5 to 6 meters.

Long tube evaporators (Falling film evaporators)

Construction and working

principle the heating unit consists
of steam- jacketed tubes, having a
length to diameter ratio of about
140 to 1, so that a large
evaporator may have tubes 50
mm in diameter and about 7 m in
length.
The liquor to be evaporated is
introduced at the top of the
evaporator tubes and the liquor
comes down due to gravity.
The concentrate and vapor leaves
the bottom. They are separated in
a chamber where the concentrate
is taken out through product
outlet and vapor from vapor
outlet.

Advantages of long tube evaporator(s)

since the movement of the film is
assisted by gravity, more viscous
liquid can be handled by falling film
evaporator.
(i) Very high film velocity reduces
boundary layers to a minimum
giving improved heat transfer.
(ii) The use of long narrow tubes provides large surface area for heat transfer.
(iii) Because of increased heat transfer efficiency, a small temperature gradient is necessary with less risk of damage to
thermo labile materials.
(iv) Although the tubes are long, they are not submerged, as in the short-tube evaporator; so that there is no elevation of
boiling point due to hydrostatic head.

Disadvantages
(i) Expense to manufacture and install the instrument is high.
(ii) Difficult to clean and maintain.
(iii) From the operational point of view the feed rate is critical. If too high, the liquor may be concentrated
insufficiently, whereas, if the feed rate is to low, the film cannot be maintained and dry patches may form on the
tube wall.
Factors affecting evaporation:
(vi) Temperature:
Heat is necessary to provide the latent heat of vaporization, and in general, the rate of
evaporation is controlled by the rate of heat transfer. Rate of heat transfer depends on the
temperature gradient.
Many pharmaceutical agents are thermo labile. So the temperature that will cause the least
possible decomposition should be used.
E.g. many glycosides and alkaloids are decomposed at temperature below 1000C.
E.g. Hormones, enzymes and antibiotics are extremely heat sensitive substances. E.g. Malt
extract (containing enzyme) is prepared by evaporation under reduced pressure to avoid loss of
enzymes.
Some antibiotics are concentrated by freeze-drying.
(vii) Temperature and time of evaporation
Exposure to a relatively high temperature for a short period of time may be less destructive of
active principles than a lower temperature with exposure for a longer period.
Film evaporators used a fairly high temperature but the time of exposure
is very short. An evaporating pan involve prolonged heating.
(viii) Temperature and moisture content
Some drug constituents decompose more rapidly in the presence of moisture, especially at a
raised temperature (by hydrolysis). Hence, evaporation should be carried out at a low
controlled temperature, although the final drying can be performed at higher temperature when
little moisture remains.
E.g. Belladonna Dry Extract is an example of this type.
(ix) Type of product required
Evaporating pans or stills will produce liquid or dry products, but film evaporators will yield
only liquid products. So a dilute extract can be first concentrated in a film evaporator and then
the concentrated extract may be died in an evaporating pan.
(x) Effect of concentration
As the liquor becomes concentrated, the increasing proportion of solids results in elevation of
the boiling point of the solution. This leads to a greater risk of damage to thermo labile
constituents and reduction of the temperature gradient.
In general concentrated solutions will have increased viscosity, causing thicker boundary
layers, and may deposit solids that may build up on the heating surface that reduce heat
transfer.
All these problems may be minimized by turbulent flow condition.
 CHAPTER=7
Distillation
Distillation is the process of converting liquid into its vapours by heating
and recovering it again into liquid by condensing the vapour.

Difference between Evaporation and Distillation:

Distillation Evaporation
i) Distillation occurs at the Evaporation occurs below the
boiling point of liquid. boiling point.
ii) Collection and Collection and condensation
condensation of vapour of vapour is not done.
is done.
iii) Vapour is formed Vapour is formed at the
throughout the liquid surface of liquid, evaporation
is surface phenomenon.
iv) Distillation is carried out Evaporation is carried out
when condensed vapour when concentrated residue is
is required. required.

 Simple distillation:
Simple distillation is a process of converting a liquid into its vapour in a distillation
still, transferring the vapour to another place and condensing it again into liquid.
The liquid to be purified is taken in the distillation flask fitted with a thermometer
and a water condenser. The flask is heated on water, oil or a sand bath depending
upon the boiling point of the substance being distilled. The vapour of the liquid get
condensed when pass through the condenser and are collected in the receiver. The
impurities remain in the distillation flask.

Applications:
 Organic solvents are purified by distillation.
  To separate non-volatile solid from volatile liquids such as alcohol,
ether, benzene etc.
 It is also used to recover alcohol from the extract during the
separation of dry extract.

 Fractional distillation
Fractional distillation is used for separating a mixture of two or more
miscible liquid mixed with each other and having different boiling
points. During the process of fractional distillation, the boiling point of
the mixture is increased gradually as more and more components having
low boiling point is distilled first. The mixture can be separated into pure
components by fractional distillation.

In the process, the mixture of miscible liquid to be separated is placed in

the distillation falsk. On heating, the mixture gets converted into vapours
which enters into the fractionating column. The purpose pf fractionating
column is to increase the cooling surface and to provide obstructions to
the passage of asending vapour and decending liquid. The result of this
vapour liquid contract is the the more volatile components tend to be
transferred to the liquid. The condensed vapour of the liquid having low
boiling point enter into condenser. The condensed liquid is falls into the
receiver.

Applications:
 It is used for the manufacturing of ethyl alcohol.
 It is used for separation of miscible liquid such as alcohol and water,
acetone.
 It is used for the preparation of volatile oils like lemon and orange
oils.

 Vacuum distillation:
This method is applicable for thermolabile substance or for substance
which decompose on boiling at atmospheric pressure. When vapour
pressure equal to the atmospheric pressure. So boiling point of the liquid
may be lowered to the desired temperature by reducing pressure on its
surface.
In this process of distillation chances of superheating and bumping are
greatly increased due to the reduced pressure. This difficulty may be
Overcome by the use of a special type of distillation flask, one arm of
which carries a capillary tube, which is partially closed at the upper end
and by a pressure tubing screw clip arrangement to regulate air. The
pressure inside the apparatus is reduced by a vacuum pump. A
manometer is also used to regulate the pressure. The Claisen flask is
connected to a receiver through condenser. Heating of Claisen flask is
not started until the desired vacuum has beenattained.

Applications (i) It is used for separating or purification of liquids which

undergo decomposition at their boiling point.
(ii) It is used for concentrating and drying of extracts which undergo
decomposition of active constituents when heated under normal
atmospheric
pressure.
(iii) It is also used for preparation of light porous product

Vacuum stills:
Vacuum stills are used for large scale distillation under reduced
pressure. It is used for those substances which have high boiling point at
atmospheric pressure and get destroyed at high temperature
Vacuum stills are made up of metals such as copper or stainless steel.
which can withstand a high vacuum. A glass observation window is
provided for the operator to see the progress of the distillation. A tap is
provided near the hood of the still for filling the still. Two receivers are
used to collect the distillate without stopping the distillation. A vacuum
pump is used for reducing the pressure in the vacuum still.

Application:
(i) It is used for concentrating and drying of extract which undergo
docomposition of active constituents when heated under normal
atmospheric pressure.
(ii) It is also used for the distillation of thermolabile substances.
Ques: What is steam distillation? What are its applications?
Steam distillation involves the distillation of substances in a current of
steam. The technique is applied to those substances which are steam
volatile, insoluble in water, have a fairly high vapour pressure at 100°C
and contain non-volatile impurities.
The substance to be distilled is placed in the flask.
Flask is heated just to boil the contents and steam from the generator is
passed through it. The vapours of the pure compound mixed with steam
pass over and are condensed while passing through the water
condenser. The pure compound along with water is collected in a
receiver.
The distillate forms two layers and the florentine receiver helps to
separate these layers. The main advantage of this method is that the
chances of decomposition of active constituents is less because the
process is carried out at a temperature less than 100°C

(i) It is used for the preparation of aromatic waters.

(ii) It is also used for purification of glycerin, fatty acids and other
volatile oils like terpentine oil.
(iii) It is also used for distillation of liquids which are immiscible
with water.

Water in pharmaceutical practice as per 1.P.

(i) Purified water
(ii) Water for injection
(iii) Sterile water for injection.

(i) Purified Water: Water which is free from volatile and non-Water
for injection volatile impurities is called purified water. It is
prepared from drinking water by distillation or by use of ion-
exchange resins or by reverse osmosis. Such water must comply
with limit tests for chlorides, sulphates, calcium, copper, lead,
iron, oxidizable matter, total solids and ammonia. It is liable to get
contaminated by micro-organisms, hence purified water should
not be used for preparation meant for parenteral administration. It
is a colourless, odourless, tasteless, clear liquid. The pH ranges
from 4.5 to 7.0. It is also free from dissolved carbon dioxide. It
should be stored in tightly closed containers. It is a practice that
whenever distill water is prescribed, purified water is to be
dispensed.
 (ii) Water for Injection: Water which is free from volatile and
non- volatile impurities, pyrogens and micro-organisms is called
water for injection. It is obtained by distillation of petable water,
purified water or distilled water. It contains no added substances.
The purity specification limits, the quantities of chloride, sulphate,
calcium, heavy metal ions, carbon dioxide, ammonia, oxidizable
substances and total solids. IP. Describes water for injection as
colourless, odourless, tasteless, clear liquid. The pH ranges from
5.0 to 7.0. It should be stored in tightly closed glass containers
and must be used within 24 hours for the preparation of parenteral
products. The heating and storing of water for injection at 80°C
will prevent bacterial growth. It is used for the preparations of
parenteral dosage form.

(iii) Sterile water for Injection : I.P. describes sterile water for
Injection as a colourless, odourless, tasteless clear liquid which is
sterilized and suitably packed. It is free from pyrogens and micro-
organisms. The pH range is between 4.5 to 7.5. It must comply
with the tests for sterility. It should also comply with the tests for
CO2, Cl-, So4--, NO3-,, NO2-, NH4+,ca2+ and heavy metal 1ons. It
should be stored in single dose containers not larger than one litre
in size. The solid contents should not be more than 0.004% (w/v)
for sterile water tor injection in glass container. Higher total solid
content is permitted in sterile water for injection to allow for the
material leached from the glass container during sterilization
process.

Distilled water

Distilled water and water for injection can be prepared continuously

without the impurities of gases, hydrolysis of salts, etc. by using
distillation stills. A distillation still used for the manufacturing of
distilled water. It consists of a boiler which is made of cast iron. It is
connected to condenser through the baffles. The condensed tubes and
baffles which come in contact with vapours and purified water are of
stainless steel. For heating. it has heating elements or coils. The cooled
water enters at the bottom of condenser and is heated by condensing
vapours. The flow rate is adjusted in such a way that water gets heated at
90-95°C betfore it enters the boiler. The top of the condenser jacket is
open for removal of gases. A constant level device is fitted in such a way
that only the heated water free from gases enters the boiler. The stills
containing the bafiles are used for the manufacturing of purified water
free from pyrogens and other impurities (i.e.,water for injection). The
purified water free from pyrogen is filled into ampoules and after sealing
they are sterilized in an autoclave at a temperature of 115°C for 30
minutes. When water for injection free from carbon dioxide is required,
the distillate should be boiled for 10 minutes with minimum exposure to
air which can be done by covering the mouth of the flask, Distilled water
may be prepared from drinking water by distillation, by use of ion
exchange resins. Ion exchange process are also used for the preparation
of purified water which can be used for all pharmaceutical purpose
except where water for injection is required. This is due to the fact that
during ion exchange processes, the pyrogens are not effectively
removed.
 CHAPTER=8

DRYING
Drying is defined as the removal of liquid from a solid by thermal
method. When large amount of liquid is evaporated from a solution or
slurry the process is called ‘evaporation’. When very small amount of
liquid is evaporated from solids the process is called ‘drying’. The final
product is a ‘dried solid’.

Purpose of drying in pharmaceutical industries

1. Drying is most commonly used in pharmaceutical industries in the
preparation of granules, which can be packed in bulk or
compressed into tablets or filled in capsules.
2. Drying is required for processing of materials like, drying of
aluminium hydroxide, spray drying of lactose and preparation of
powdered extracts.
3. Drying is used to reduce the bulk weight that lowers the
transportation and storage costs of that material.
4. Drugs obtained from plant and animal sources, when dried,
becomes more friable. Thus drying helps in size reduction of
natural drugs.
5. Animal and vegetable drugs are preserved against mold growth in
dried condition.
6. Dried products often are less many stable than moist ones as in the
case of effervescent salts, aspirin, hygroscopic powders, ascorbic
acids and penicillin.

CLASSIFICATION OF DRYERS

Classification based on solid handling

 Material Not Agitated Material Agitated

Static bed dryers Moving bed dryer Fluidized bed dryer Pneumatic dryer

Batch Continuous Batch Continuous Batch Continuous Continuous

type type type type type type type

Tray & Truck Tunnel dryers Vacuum Rotary dryers Vertical Horizontal Spray dryers
dryers tumble dryers vibrating
Belt dryers Turbo tray Flash dryer
dryers conveyor
Vacuum shelf dryers
dryers
dryer Festoon dryers
Pan Vibrating
Drum dryers conveyor dryers Vertical
Freeze dryers dryers
dryers
Tower & cascade
dryers
Screw conveyor
dryers

Classification of dryers, based on methods of solids handling

Classification based on heat transfer mechanism
1. Convection dryers
(a) Tray or shelf dryers
(b) Tunnel dryers
(c) Rotary dryers
(d) Fluidized bed dryers
2. Conduction dryers
(a) Vacuum oven (b) Freeze dryers
3. Radiant heat dryers
(a) Infra-red dryers

TRAY DRYER or Truck Dryer

Construction: It consists of a small cabinet or a large compartment in
which trays containing wet materials are placed. The compartment wall
is insulated to reduce heat loss.

1. In tray dryers the trays are directly placed inside the cabinet.
2. The truck dryer the trays are loaded on to the trucks (shelves on
wheel) and then the trucks are introduced inside the heating
cabinet.
The bottom of the trays are either perforated or having wire-mesh
bottom.
 Direction Air outlet
vanes Fan

Heater

Fresh air
inlet

Truck carrying
trays
Wheel
Fig. Truck dryer

1. The material is heated by hot air circulated by means of fans that

removes the humid air from the cabinet.
The trays containing the load remain in the dryer until drying is
complete, after which they are withdrawn, emptied and recharged for
drying the next batch.

Energy sources: Dry air can be heated either by electricity or steam.

Applications
1. Drying of crude drugs, chemicals, powders, tablet granules etc.
2. It is a batch process and materials can be handled separately.
ROTARY DRYERS
Construction
Feed inlet

Drive gear Dryer shell

Air outlet Air heater

Air
inlet

Motor
Dry product
Fig. Rotary dryer outlet
It is a cylindrical shell (10 m length) mounted with a slight slope so that
the material will move through the shell as it is slowly rotated at about
10 rpm. To improve contact the shell contains baffles or flights, which
lift the solids and spill the particles through the air stream.
The hot air flows counter current to the flow off material.
Application
It is used for continuous drying on a large scale of any powdered or
granular solid.

FLUIDIZED BED DRYER

Principle C E
D
Let us consider a situation where a bed of B

granules is placed over a perforated bottom log(P)

container and hot air is flown from bottom A

through the bed. The pressure drop (P) log(V)

across the bed and the air velocity (V) are measured. If the air velocity is
gradually increased and P is plotted against V then the following curve
is observed.
1. Point A: When the air velocity is very low flow takes place
between the particles without causing any disturbance.
2. Point B: When the velocity is increased to a certain value the
frictional drag on the particles become equal the force of gravity of
the particle.
3. Point C: Rearrangement of the particles occurs to offer least
resistance.
4. Point D: Eventually the particles are suspended in the air and can
move, P decreases slightly because of greater porosity.
5. Further increase in the air velocity causes the particles to separate
and move freely, and the bed is fully fluidized. Any additional
increase in velocity separate the particles further, i.e. the bed
expands, without appreciable change in P until E.
6. In the D-E region the air flows
Air outlet
through the bed in the form of Air Inlet Fan
bubbles – the term boiling bed is
generally used for this stage.
Filter
7. Above point E the solid particles bag
Air
entrain into the gaseous phase and the heaters
particles float in the gas. Fluidized
solids
Construction
Two types of fluidized bed dryers are there Fig. Fluidized bed dryer
1. vertical fluidized bed dryer – for
batch process
2. horizontal fluidized dryer – for continuous process
The dryer consists of:
1. Air handler: This is a source of dry and hot air. It is also attached
by means of heating and dehumidifying air, if necessary.
2. Plenum: It consists of a screen or plate to distribute the incoming
air as it enters the dryer.
3. Product container: This container holds the product that is to be
dried.
4. Expansion chamber: This chamber is situated above the product
container and holds the suspended material.
5. Filter: The upper part of the expansion chamber has bag filters. It
prevents fines from escaping into the atmosphere or collecting on
the blades that pulls the air through the dryer.

Applications
1. Wet granulation:
1. Fluidized bed dryers are used to dry the previously prepared wet
granules.
2. Powders are agglomerated in the drying chamber by spraying
liquid binder over it, while the hot air dries the agglomerates to
form dry granules.
2. Coating of tablets
The fluidized bed dryer can be used for coating granules also. This
technique is called Wurster technique.
In fluidized condition the powder is coated by coating solution sprayed
from the nozzles. As the particles are coated they become heavier. When
the mass developed becomes higher than the drag force given by the
fixed air velocity the particles no longer floats. They fall back, which is
then collected as product.

Advantages
1. Efficient heat and mass transfer facilitate high drying rates.
Heating time of thermolabile materials is minimized.
2. Individual particles of the bed get dried in the fluidized state. So,
most of the drying will be at constant rate and the falling rate
period is very short.
3. Temperature can be controlled uniformly.
4. A free-flowing product is obtained.
5. Since the bed is not static, free movement of individual particles
eliminates the risk of soluble materials migrating.
6. Short time yields a high output from a small floor space.

Disadvantages
1. Turbulence of fluidized state may produce fine particles due to
attrition.
2. Fine particles lead to segregation, so they must be collected by bag
filters.
3. Static charges may be produced due to vigorous movement of
particles in hot dry air.

VACUUM DRYER
Conduction is used as the
principle method of heat
transfer in dryers that are Condenser
operated under vacuum. Water or
steam jacket Condensate
receiver

Connection to
vacuum pump
Fig. Vacuum dryer
Convection cannot take place when air is nearly absent.
Construction
It is a jacketed vessel through which steam or hot water is passed. The
vessel can be closed airtight. The oven is connected through a condenser
and receiver to a vacuum pump. The supports of the shelves form part of
the jacket, giving a larger area for heat conduction. Materials to be dried
are kept in a tray and placed on the shelves. Hot water or steam is passed
through the jacket, a vacuum pump is connected to the chamber.
Advantages:
1. Drying takes place at low temperature, so thermolabile materials
can be dried.
2. It reduces the risk of oxidation during drying.
3. It produces porous and friable granules. [N.B. Because under
vacuum the vapor forms bubbles and in this condition the material
is dried.]
4. The solvent can be recovered from the condenser.

Disadvantages
1. Heat coefficients are low. Most of the heating takes place by
conduction, some is from radiation from the wall of the jacket
around. So the drying rate is slow.
2. Labor and running costs are high.
Applications:
1. To dry a thermolabile material like Penicillin.
2. To produce porous form such as dry extract.
3. To recover the solvent, for example to recover ethanol from
ethanol extractives.

FREEZE DRYER
Principle
The temperature and pressure of the
material is reduced below the triple point of Liquid

solvent to be dried. Under these conditions, Pressure

Solid Triple point
any heat transferred is used as latent heat
and the ice sublimes directly to vapor state Vapor

(without formation of liquid state). Temperature

Triple point of pure water is 4579 m of Hg
and 0.00990C. Pharmaceutical products remain in solution. In this case
the pressure and temperature below which water evaporates directly
from ice to vapor state is called eutectic point. In freeze dryer the
pressure and temperature is maintained well below the eutectic point.
Generally it is carried out at –100C to –400C, and at pressure of 2000 to
100 m Hg.
Construction
Freeze dryer consists of
1. a chamber for vacuum drying:
Two types of chambers are there, one for batch type and another for
continuous type operation.
2. a vacuum source:
Vacuum is achieved either by vacuum pump or by steam ejector or a
combination of two.
3. a heat source:
Heat is provided by conduction or radiation.
4. a vapor removal system:
For removal of water vapor condensers, desiccants, pumps or
scrapper blades are employed.

Stages of freeze drying process

(a) Preparation and pretreatment:
 Protein solutions take 8 to 10 Drying Shelves
chamber
times longer period than pure Condenser
water. Therefore, in such cases, it
is desirable to concentrate the
Door Vacuum
solution under normal vacuum pump
tray dryer.
(b) Pre-freezing
Heating
The aqueous solutions to be System
dried are packed in vials, Refrigerator

ampoules or bottles. They are Fig. Industrial freeze dryer

then cooled to solidify the water. Cooling can be done by using cold-
shelves (–500C), alcohol baths (–500C) or liquid nitrogen bath (–
1950C).
1. Thinner the layer of frozen material higher is the drying rate. The
usual thickness is kept at 0.5 to 0.75 inches.
2. Low freezing rates produces larger crystals of ice. Sublimation of
water from this material leaves large pores. So freezing rate is
generally maintained at 3 to 250C/min resulted in a product having
pore size of 1 to 45 m.
(c) Primary drying (Sublimation of ice under vacuum)
A vacuum of 0.5 bar is applied on the frozen materials. The
temperature is increased to 300C within 2 hours. Then the temperature
is kept constant. During this stage around 98 to 99% water is removed
from the materials.
(d) Secondary drying (Removal of residual moisture under high vacuum)
Temperature is maintained at 300C continuously and vacuum is
lowered to a pressure of 0.07 bar. The rate of drying is very low it
takes 10 to 20 hours to dry 1% moisture.
(e) Packing
Inert gas is introduced inside the dryer to break the vacuum. Then the
vials and ampoules are sealed within the dryer to reduce the contact of
atmospheric gases.
Advantages
1. Drying takes place at a very low temperature, so that the enzyme
action is inhibited, and decomposition (e.g. hydrolysis) is
minimized.
2. The solution is frozen, so that the final dry product is a network of
solid occupying the same volume as the original solution. Thus
there is no case-hardening and the product is light and porous.
3. The dried products are readily re-dissolved or re-suspended by the
addition of water prior to use (this procedure is termed as
reconstitution).
4. The solutions do not concentrate during drying (like in other
drying methods). Hence salts do not concentrate and denature the
proteins present in the same solution.
5. Under high vacuum there is no contact with air, and oxidation is
minimized.

Disadvantage
1. It produces a very hygroscopic product, hence should be sealed in
the final package within the dryer.
2. The process is very slow.
3. The instruments are very costly.

Applications:
1. Maintenance and preservation of microbial culture.
2. Solution of penicillin can be stored at 0 – 20C and used within two-
three days, but if freeze dried then it is stable for several months.
3. To produce fibrin foam [N.B. Fibrinogen is dissolved in sodium
chloride injection and whipped into a foam that is then clotted by
addition of human thrombin. The foam is then freeze dried].
4. To prepare gelatin sponge [N.B. A solution of gelatin containing
traces of formaldehyde is foamed, freeze dried, sterilized and used
as surgical dressing.]
5. Used to dry sera, blood products, certain enzymes, plant extracts,
diagnostics, mammalian tissues useful in skin and bone graft
surgery.
 CHAPTER=9
Sterilization
Sterilization are essential for ensuring that medical and surgical
instruments do not transmit infectious pathogens to patients. Because
sterilization of all patient-care items is not necessary, health-care
policies must identify, primarily on the basis of the items’ intended use,
whether cleaning, disinfection, or sterilization is indicated.

Methods of sterilization
The various methods of sterilization are:
1. Physical Method: (a) Thermal (Heat) methods (b) Radiation method
(c) Filtration method
2. Chemical Method
3. Gaseous method

Heat Sterilization:
Heat sterilization is the most widely used and reliable method of
sterilization, involving destruction of enzymes and other essential cell
constituents. The process is more effective in hydrated state where under
conditions of high humidity, hydrolysis and denaturation occur, thus
lower heat input is required. Under dry state, oxidative changes take
place, and higher heat input is required. This method of sterilization can
be applied only to the thermostable products, but it can be used for
moisture-sensitive materials for which dry heat (160- 180°C)
sterilization, and for moisture-resistant materials for which moist heat
(121-134°C) sterilization is used. The efficiency with which heat is able
to inactivate microorganisms is dependent upon the degree of heat, the
exposure time and the presence of water. The action of heat will be due
to induction of lethal chemical events mediated through the action of
water and oxygen. In the presence of water much lower temperature
time exposures are required to kill microbe than in the absence of water.
In this processes both dry and moist heat are used for sterilization.

Dry Heat Sterilization: Examples of Dry heat sterilization are:

1. Incineration
2. Red heat
3. Flaming
4. Hot air oven
It employs higher temperatures in the range of 160-180°C and requires
exposures time up to 2 hours, depending upon the temperature
employed. The benefit of dry heat includes good penetrability and non-
corrosive nature which makes it applicable for sterilizing glass-wares
and metal surgical instruments. It is also used for sterilizing non-aqueous
thermo-stable liquids and thermostable powders. Dry heat destroys
bacterial endotoxins (or pyrogens) which are difficult to eliminate by
other means and this property makes it applicable for sterilizing glass
bottles which are to be filled aseptically.

Hot-air oven:
Dry heat sterilization is usually carried out in a hot air oven, which
consists of the following:
(i) An insulated chamber surrounded by an outer case containing
electric heaters.
(ii) A fan
(iii) Shelves
(iv) Thermocouples
(v) Temperature sensor
(vi) Door locking controls.

Operation:
(i) Articles to be sterilized are first wrapped or enclosed in
containers of cardboard, paper or aluminium.
 (ii) Then, the materials are arranged to ensure uninterrupted air
flow.
(iii) Oven may be pre-heated for materials with poor heat
conductivity.
(iv) The temperature is allowed to fall to 40°C, prior to removal of
sterilized material. Moist Heat Sterilization: Moist heat may be
used in three forms to achieve microbial inactivation.

Autoclaving:
Moist heat sterilization involves the use of steam in the range of 121-
134°C. Steam under pressure is used to generate high temperature
needed for sterilization. Saturated steam acts as an effective sterilizing
agent. Steam for sterilization can be either wet saturated steam
(containing entrained water droplets) or dry saturated steam (no
entrained water droplets).

An Autoclave Autoclaves use pressurized steam to destroy

microorganisms, and are the most dependable systems available for the
decontamination of laboratory waste and the sterilization of laboratory
glassware, media, and reagents. For efficient heat transfer, steam must
flush the air out of the autoclave chamber. Before using the autoclave,
check the drain screen at the bottom of the chamber and clean if blocked.
If the sieve is blocked with debris, a layer of air may form at the bottom
of the autoclave, preventing efficient operation. Autoclaves should be
tested periodically with biological indicators like spores of Bacillus
stearothermophilus to ensure proper function. This method of
sterilization works well for many metal and glass items but is not
acceptable for rubber, plastics, and equipment that would be damaged by
high temperatures. Autoclaves, or steam sterilizers essentially consist of
following:
1. A cylindrical or rectangular chamber, with capacities ranging from
400 to 800 litres.
2. Water heating system or steam generating system
3. Steam outlet and inlet valves
4. Single or double doors with locking mechanism.
5. Thermometer or temperature gauge
6. Pressure gauges Operation For porous loads (dressings) sterilizers are
generally operated at a minimum temperature of 134°C for one hour, and
for bottled fluid, sterilizers employing a minimum temperature of 121°C
are used. Ensure that there should be sufficient water in the autoclave to
produce the steam. The stages of operation of autoclaves include air
removal, steam admission and sterilization cycle.

RADIATION STERILIZATION
Many types of radiation are used for sterilization like electromagnetic
radiation (e.g. gamma rays and UV light), particulate radiation (e.g.
accelerated electrons).The major target for these radiation is microbial
DNA. Gamma rays and electrons cause ionization and free radical
production while UV light causes excitation. Radiation sterilization with
high energy gamma rays or accelerated electrons has proven to be a
useful method for the industrial sterilization of heat sensitive products.
But some undesirable changes occur in irradiated products, an example
is aqueous solution where radiolysis of water occurs.

Radiation sterilization is generally applied to articles in the dry state;

including surgical instruments, sutures, prostheses, unit dose ointments,
plastic syringes and dry pharmaceutical products. UV light, with its
much lower energy, and poor penetrability finds uses in the sterilization
of air, for surface sterilization of aseptic work areas, for treatment of
manufacturing grade water, but is not suitable for sterilization of
pharmaceutical dosage forms. Gamma ray Sterilizer: Gamma rays for
sterilization are usually derived from cobalt-60 source.
This source is housed within a reinforced concrete building with 2 m
thick walls. Articles being sterilized are passed through the irradiation
chamber on a conveyor belt and move around the raised source.
Ultraviolet Irradiation: The optimum wavelength for UV sterilization is
260 nm. A mercury lamp giving peak emission at 254 nm is the suitable
source of UV light in this region. Electron Accelerator There are two
types of electron accelerator machines, the electrostatic accelerator
which produces electrons with maximum energies of 5 MeV, and the
microwave linear accelerator which produces electrons with maximum
energies of 10 MeV. Higher energies cause better penetration into the
product but there is a risk of induced radiation. A high energy electron
beam is generated by accelerating electrons from a hot filament down an
evacuated tube under high potential difference, and then additional
energy is imparted to this beam in a pulsed manner by a synchronized
traveling microwave. Articles to be sterilized are arranged on a
horizontal conveyor belt and are irradiated from one or both sides.
 CHAPTER=10
Aseptic Technique
Aseptic technique means using practices and procedures to prevent
contamination from pathogens. It involves applying the strictest rules to
minimize the risk of infection. Healthcare workers use aseptic
technique in surgery rooms, clinics, outpatient care centers.

Surgical technique:
Surgical skill does not negate the need for aseptic technique but the
competence with which the tissues are handled is closely tied to the
degree of contamination a wound can overcome. To assure maximum
blood supply to the healing tissue, it must be handled gently with either a
skin hook or toothed tissue forceps, and unnecessary tension on the
wound edges during closure avoided. Hemostasis should be achieved in
a manner that does not compromise blood supply, implant excessive
amounts of suture, or induce unnecessary thermal damage. Electro
cautery is an indispensable tool but it must be used judiciously.
Excessive thermal destruction of tissue is associated with an increased
risk for infection.43 Consider bipolar cautery, which directs current
between the tips of the forceps, and produces significantly less tissue
necrosis than monopolar cautery at comparable energy settings. 58 Avoid
extensive thermal damage by tying off large-diameter vessels or
muscular arteries. When possible, use the smallest effective
monofilament suture and limit unnecessary suture, particularly braided
silk, which enhances the virulence of staphylococci 10 000-fold.
Aseptic technique demands the use of sterile gloves. Although their
effectiveness in the control of infection in regard to minimally
invasive spinal injections has never been demonstrated, some have
advocated the use of masks, hats, and gowns.
A sterile cover for the C-arm image intensifier allows the physician to
control and direct the image during the periprocedural period. In
addition, this prevents contaminating detritus from falling onto the
sterile field from the equipment. A sterile, long, 6- to 12-inch, radio-
opaque pointer, combined with a skin marking pen enables the
injectionist to mark the proposed skin entry site in a radiation safe
manner.
Aseptic techniques are those that do some or all of the following:

 Remove or kill microorganisms from hands and objects

 Employ sterile instruments and other items
 Reduce a patients risk of exposure to microorganisms

Aseptic technique refers to the practices performed immediately before

and during a clinical procedure. They include:

 Handwashing
 Surgical scrub
 Using barriers (personal protective equipment)
 Patient prep
 Maintaining the sterile field
 Using safe operative technique (making small incisions, avoiding
trauma to tissue and surrounding structures, and controlling
bleeding)
 Maintaining a safer environment in the surgical/procedure area
Nurses in all practice settings need to have a good understanding of the
importance of hand asepsis and the proper technique for achieving skin
preparation of the surgical or procedural site, Denholm adds. They also
need to understand the basics of caring for and cleaning surgical
instruments including the decontamination process and how to evaluate
packaging systems to ensure conditions have been met for sterilization,
storage, and handling of sterile instruments and supplies.

Glove use is important and gloves must be used appropriately. In a study

measuring how the improper use of gloves limits compliance to hand
hygiene and exposes patients to infection
 CHAPTER=11
Tablets

Tablets are solid dose pharmaceutical preparation containing drug

substances usually prepared with the aid of suitable pharmaceutical
excipients. They may vary in size, shape, weight, hardness, thickness,
disintegration and dissolution characteristics and in other aspects,
depending on their intended use and method of manufacture. It used to
provide systemic administration of therapeutic agents. Tablets are
prepared primarily by compression of granules or powder blends, with a
limited number prepared by moulding. Most tablets are used in the oral
administration of drugs. Many of these are prepared with colourants and
coatings of various types. Other tablets, such as sublingual, buccal, or
vaginal tablets, are prepared to have features most applicable to their
particular route of administration.

Advantages of Tablets
 Tablets are elegant in appearance and convenient to use.
 They are superior to other dosage forms with respect to chemical,
physical and microbiological stability.
 Tablets provide stable and an accurately measured dosage of drug
substance to patients.
 Tablets can be formulated to protect unstable drug substances or
disguise unpalatable excipients.
 Tablets are generally inexpensive to manufacture.
 It is easier to mask the unpleasant taste of some APIs in tablets
thus improving patient acceptability.
 Tablets may be formulated to contain two or more drug substances
(even if they are physically or chemically incompatible), thus reducing
multiple tablet use.
 Tablets may be easily manufactured to show product identification
using coloured coatings, embossed markings, and printing.
 Tablets may be designed to release their active substance at a
particular site within the gastrointestinal tract to reduce side effects,
 promote absorption at that site or provide a local effect (e.g. ulcerative
colitis).
 With the exception of proteins which are denatured in the
gastrointestinal tract, all classes of therapeutic agents may be
administered orally in the form of tablets
Disadvantages of Tablets
 The manufacture of tablets requires a series of unit operations
(weighing, milling, drying, mixing etc.) thus there is an increased level
of product loss at each stage in the formulation process.
 The absorption of medicament from tablets is dependent on
physiological factors, such as gastric resident/emptying time, and thus,
vary from one .patient to another.
 The compression properties of certain drug substance are poor and
may present problems in their subsequent formulation and manufacture
as tablets.
General Properties of Tablets
 A tablet must be strong and hard to withstand mechanical shock
during manufacturing, packing, shipping, dispensing and use.
 The drug content of the tablet must be bioavailable that is, the
tablet must be able to release its content in a predictable and
reproducible manner.
 The tablet must be chemically and physically stable to maintain its
chemical and physical attributes during manufacture, storage, and use.
 The tablet should have elegant product identity which is free from
any tablet defect.
 Tablets must be uniform in weight and in drug content.

Types of tablets
The various tablet types are described as follows:

1. Compressed tablets represent a significant proportion of tablets that are

clinically used to provide systemic administration of therapeutic agents
either in an uncoated state or in a coated state. These tablets are
designed to provide rapid disintegration in the gastric fluid following
ingestion hence, allowing rapid release of the drug and, ultimately,
systemic absorption of the dosage form.

Compressed tablets are formed by compression of powdered, crystalline,

or granular materials into the required geometry by the application of
high pressures, utilizing steel punches and die. In addition to the Active
Pharmaceutical Ingredients, compressed tablets usually contain a
number of pharmaceutical excipients e.g., bulking agents, disintegrants,
binders, lubricants, controlled-release polymers and other miscellaneous
adjuncts such as colourants and flavourants which serve different and
specialized purpose during tablet manufacture, storage, and use.
Examples of compressed tablets include tablets for oral, buccal,
sublingual, or vaginal administration.

2. Film-coated tablets are conventional tablets coated with a thin layer

of polymer (e.g., hydroxypropyl methylcellulose, hydroxypropyl
cellulose) or a mixture of polymers (e.g., Eudragit E100) capable of
forming a skin-like film. The film is usually coloured and also
impacts the same general characteristics as sugar coating with the
added advantage of being more durable, less bulky, and less time-
consuming to apply. By its composition, the coating is designed to
break and expose the core tablet at the desired location in the
gastrointestinal tract.

3. Enteric-coated tablets are compressed tablets that have delayed-

release properties. They are coated with polymeric substances (such
as cellulose acetate phthalate/cellulose acetate butyrate;
hydroxypropylmethylcellulose succinate; and methacrylic acid
copolymers) that resist solution in gastric fluid but disintegrate and
allow drug dissolution and absorption in the intestine.

Tablet Excipients:
In tablet formulation, many materials are usually combined at various
quantities to produce a tablet that is of good standard. These materials
serve different and specialized functions in the tablet. The type and
 quantity of each raw material used is dependent on the intended tablet
type and formulation technique. Tablet Excipients include:

 Binders /granulating fluid: E.g. acacia gum, tragacanth, corn

starch, methylcellulose, gelatin, panwar gum, ghatti gum, mucilage of
isapol husks, carboxymethylcellulose, methylcellulose,
polyvinylpyrrolidone and sugars, such as sucrose, glucose, dextrose,
molasses, and lactose etc.
 Bulking agents/ diluents/fillers – g., anhydrous lactose, spray dry
lactose, microcrystalline cellulose, corn starch, dicalcium phosphate,
calcium sulfate, lactose, cellulose, kaolin, mannitol, sodium chloride,
etc.
 Disintegrating agents – e.g., starch, clays, celluloses, algins,
gums, and cross-linked polymers (croscarmellose, crospovidone, and
sodium starch glycolate) etc.
 Lubricants – e.g., metallic stearate, magnesium stearate, calcium
stearate, stearic acid, hydrogenated vegetable oil, corn starch, boric
acids, sodium chloride, sodium lauryl sulphate etc.
 Glidants – e.g., colloidal silicon dioxide Cab-o-sil, Talc etc.
 Colouring agents
 Flavoring agents– e.g., Aspartame.
 Adsorbent – e.g., silicon dioxide, magnesium oxide, starch,
magnesium silicate etc.

Manufactured of tablets:
Tablets are commonly manufactured by one of the following
manufacturing processes:

Wet granulation
1. Milling of drugs and excipients.
2. Mixing of drugs and excipients.
3. Preparation of binder dispersion.
4. Mixing of binder solution with powder to form a coarse mass.
5. Coarse sieving
6. Drying of moist granules.
7. Sieving of the dried granules and mixing with disintegrant and
lubricant.
8. Compression into tablets.

Dry granulation Process:

1. Milling of drugs and excipients.
2. Mixing of milled powders.
3. Compression of mixed powders into slugs (big tablets).
4. Milling and sieving of the slugs.
5. Mixing with disintegrant and lubricant.
6. Compression into tablets.

Direct compression
1. Milling of drugs and excipients.
2. Mixing of powders, disintegrant and lubricant.
3. Compression into tablet

Defects of tablets are:

Lamination: Lamination is the separation of a tablet into two or more

distinct horizontal layers.
Sticking: Sticking refers to the tablet material adhering to the die wall.
Filming is a slow form of sticking and is largely due to excess moisture
in the granulation.
Cracking: Small fine cracks observed on the upper and lower center
surface of the tablets, or very rarely on the side wall are referred to as
cracks.
Chipping: Chipping is defined as the breaking of tablet edges, while the
tablet leaves the press or during subsequent handling and coating
operation.
Mottling: Mottling is the term used to describe an unequal distribution
of colour on a tablet.
Double Impression: Double impression involves only those punches,
which have a monogram or other engraving on them.
 CHAPTER=12
Capsules
Capsules are solid dosage forms in which one or more medicinal and or
inert substances are enclosed within a small shell or container generally
prepared from a suitable form of gelatin. Capsules are usually intended
to be administered orally by swallowing them whole. Occasionally,
capsules may be administered rectally or vaginally.

Advantages:
1. Neat and elegant in appearance.
2. Tasteless shell to mask the unpleasant taste/odor of the drug.
3. The contents may be removed from the gelatin shell and employed
as a pre measured medicinal powder, the capsule shell being use to
contain a dose of the medicinal substance.
4. Commonly embossed or imprinted on their surface the
manufacturer’s name and product code readily identified.
5. The ready solubility of gelatin at gastric pH provides rapid release
of medication in the stomach.
6. Packaged and shipped by manufacturers at lower cost less
breakage than liquid forms.
7. More stable and longer shelf life.

Disadvantages:
1. Capsules are not suitable for liquids that dissolve gelatin, such as
aqueous or hydro alcoholic solutions.
2. The concentrated solutions which require previous dilution are
unsuitable for capsules because if administered as such lead to
irritation into stomach.
3. Not useful for efflorescent or deliquescent materials. Efflorescent
cause capsules to soften & Deliquescent may dry the capsule shell
to brittleness.

GELATIN
Gelatin is heterogeneous product derived by hydrolytic extraction of
animal's collagen. The sources of gelatins including animal bones, hide
portions and frozen pork skin.
TYPES OF GELATIN
Type A
Type B

TYPE A - Derived from acid treated precursor that exhibits an ISO

electric point at pH-9. It is manufactured mainly from pork skin.

TYPE B - Derived from alkali treated precursor that exhibits an ISO

electric point at pH-4.7. It is manufactured mainly from animal bones.

MANUFACTURE OF EMPTY GELATIN CAPSULES:

Steps involved in making empty gelatin capsules...
• Dipping
• Spinning
• Drying
• Stripping
• Trimming
• Joining
• Polishing

• Once raw materials have been received and released by Quality

Control, the gelatin and hot demineralized water are mixed under
vacuum in Stainless Steel Gelatin Melting System.

• From receiving tanks, the gelatin solution is transferred to stainless

steel feed tanks.

• Dyes, opacifants, and any needed water are added to the gelatin in the
feed tanks to complete the gelatin preparation procedure.

• From the feed tank, the gelatin is gravity fed to Dipper section.

Dipping : Pairs of the stainless steel pins are dipped into the dipping
solution to simultaneously form the caps and bodies for 12sec. The
dipping solution is maintained at a temperature of about 50o C in a
heated, jacketed dipping pan & pins are at 22oc.
Spinning : The pins are rotated to distribute the gelatin over the pins
uniformly and to avoid the formation of a bead at the capsule ends it is
rotated 21⁄2 times by moving upward.

Drying : The gelatin is dried by a blast of cool air to form a hard shells.
The pins are moved through a series of air drying kilns, Here gently
moving air which is precisely controlled for volume, temperature, and
humidity, removes the exact amount of moisture from the capsule
halves.

Stripping : A series of bronze jaws strip the cap and body portions of the
capsules from the pins. Trimming and joining: The stripped cap and
body portions are trimmed to the required length by stationary knives.
The cap and body lengths are precisely trimmed to a ±0.15 mm
tolerance. After trimming to the right length, the cap and body portion
are joined.

• Finished capsules are pushed onto a conveyer belt which carries them
out to a container.
• Capsule quality is monitored throughout the production process
including size, moisture content, single wall thickness, and color.
• Capsules are sorted and visually inspected on specially designed
Inspection Stations.
• Perfect capsules are imprinted with the client logo on high- speed

Capsule size:
For human use, empty capsules ranging in size from 000 the largest to 5
the smallest. Generally, hard gelatin capsule are used to encapsulate
between 65 mg to 1 gram.

Types of Capsules
Hard gelatin capsules
Soft gelatin capsules

Hard Gelatin Capsules

These are used for administration of solid medicaments. The capsule
shell is prepared from gelatin. It consists of two parts i.e. body and cap.
The powdered material is filled into the cylindrical body of the capsules
and then the cap is placed over it.

Principles of capsule Filling:

Auger Fill principle:
Rectifier descends the capsules such that caps are turned up and bodies
down. From rectifying unit these are placed one by one in filling ring
kept on rotating mode. The lower ring is rotated with a suitable speed
and the hopper containing powdered drug is held over this ring. The
auger drives the drug into bodies.

Vibratory Fill Principle:

The feed is placed in the feed hopper and the capsule bodies are passed
under it. A perforated resin plate is placed in the feed hopper. Due the
vibrations of the resin plate, the powder flows freely through the pores
into bodies.

Piston – Tamp principle:

These piston tamps alter the shape of powder by compressing the
powder to form slugs. These plugs are transferred into the empty capsule
bodies with the application of slight pressure. Finally the bodies are
ejected from the machine. Compression force 50-200N

Vacuum Fill principle:

It consists of an open ended cylinder. The upper end of this is fitted with
a piston. The open end is placed in bulk powder. Vacuum is applied &
the piston is moved upward by sucking the predetermined amount of
powder which results in filling of the cylinder.

FILLING OF HARD GELATIN CAPSULES:

• Punch Method or Manual Filling.
• Hand Filling or Semi Automatic Capsules Devices.
• Automatic filling machine.
• Eli-lily
• Farmatic
• Hofliger and Karg
• Zanasi Nigris
• Parke-Davis
• Osaka
• Macofar SAS

These machine differ in there design and output Punch Method:

- Powder is placed on a sheet of a clean paper or porcelain plate using

spatula which is formed into a cake having a depth of approximately
one-fourth to one-third the length of the capsule body.

- Then empty capsule body is held between the thumb and forefinger and
punched vertically into the powder cake repeatedly until filled.
Soft Gelatin Capsules

Soft Gelatin capsules are one piece, hermetically sealed, soft gelatin
shells containing a liquid, a suspension, or a semisolid.

MANUFACTURE OF SOFT GELATIN CAPSULES:

Plate process

Rotary die process

Accogel machine
Bubble Method

Plate process:
• Place the gelatin sheet over a die plate containing numerous die
pockets.
• Application of vacuum to draw the sheet in to the die pockets.
• Fill the pockets with liquid or paste.
• Place another gelatin sheet over the filled pockets, and Sandwich under
a die press where the capsules are formed and cut out.

Rotary die press:

In this process, the die cavities are machined into the outer surface of
the two rollers.
 Gelatin is properly weighed & dispensed in melting tank under
vacuum.
Two plasticized gelatin ribbons are continuously and simultaneously
fed
with the liquid or paste fill between the rollers of the rotary die
mechanism.
As the die rolls rotate, the convergence of the matching die pockets
seals and cuts out the filled capsules.

EVALUTION OF CAPSULES:

(1) Content uniformity

(2) Disintegration test.
(3) Weight variation test
(4)Dissolution test.
(5)Moisture permeation test.
(6)Content uniformity:

The amount of active ingredient should be within the range of 85% to

115% of the label amount for 9 of 10 capsules, with no unit outside the
range of 70% to 125% of label amount.

Disintegration test for capsules:

Place 1 capsule in each of the 6tubes of the basket & suspend the
assembly in water at 37°C ± 2oC,which is repeatedly immersed 30 times
per minute.

The capsules pass the test if no residue of drug or other than

fragments of shell remains on No. 10 mesh screen of the tubes.

Weight variation test: 20 capsules are taken at random and weighed.

Their average weight is calculated, then each capsule is weighed
individually and their weight is noted. The capsule passes the test if the
weight of individual capsule falls with in 90-110% of the average
weight.
Moisture permeation test:
Acc. to U.S.P the unit dose container is packed along with dehydrated
pellets, which have the property of changing color in the presence of
moisture. The weight of test capsule is compared with the under test
capsules. Diff. in weights gives the amount of moisture absorbed.

Dissolution test for capsules:

Place 1000ml of water having a temp. of 36.5o to 37.5o into the
vessel. Place specified number of capsules in basket 7 adjust the speed to
100 rpm.
Withdraw req. volume for every 10min time interval. Filter and
determine the amount of active ingredient.
The sample passes the test if the amount of active ingredients in the
solution is not less than 70% of the stated amount.

PACKING & STORAGE OF CAPSULES:

Capsules should be packed well closed glass & plastic container &
stored at temp. not exceeding 30oc. Capsules are individually
protected by enclosing in strip & blister packaging.
In strip packing the capsule is hermetically sealed within the strips of
an aluminum or plastic film.
In blister packs, a press on the blister forces the capsule through the
backing strip.
Capsules have a larger shelf life in unopened glass bottles than in strip
pack & but this is reversed.
 CHAPTER =13
Immunological Products

Artificial immunity is induced by immunisation. This is achieved by

giving a vaccine (active immunisation) or immunoglobulin (passive
immunisation).

Active immunity
This is the stimulation of the immune mechanism to produce antibodies
by giving an antigen as a vaccine. Such vaccines may be:
 Live attenuated viruses (rubella, measles, oral polio, mumps) or
bacteria - bacillus Calmette-Guérin (BCG).
 Inactivated viruses (parenteral polio, hepatitis A) or parts of the
bacterium or virus (pneumococcal vaccine, influenza).
 Inactivated bacterial toxins (diphtheria and tetanus).
 Genetically engineered (hepatitis B vaccine).

Live attenuated vaccines

Produce longer-lasting immunity, similar but less than that produced by
natural infection. Often one dose confers long-lasting immunity;
however, they are inherently less stable than killed vaccines, with the
possibility of reversion to wild strain, as in polio. Some may spread,
enhancing herd immunity but putting at risk the immunocompromised.

Inactivated vaccines
Usually require a series of primary vaccinations followed by boosters.
Some of these vaccines have adjuvants (for example, aluminum
hydroxide, aluminum phosphate) to enhance the antibody response.
There is no risk of person-to-person spread, and the vaccines are more
stable.

Humoral immunity

Activation of B lymphocytes by an antigen produces millions of

antibodies (immunoglobulins IgG, IgM, IgA, IgD, IgE), which bind to
 and neutralise the antigen. After recognising their particular antigen,
they multiply and differentiate into plasma cells. Plasma cells produce
large amounts of antibody in the form of large glycoproteins
(immunoglobulins). Initially IgM is produced - the primary response.
This is a slow response and two injections may be needed. Further
injections of antigen will produce, after a few months, an accelerated or
secondary response producing IgG. IgG antibodies are longer-lasting.
When levels of IgG fall, a further dose of vaccine or booster will
increase IgG levels again.

Cell-mediated immunity
The cell-mediated immune response does not involve major antibody
production but does rely on antigen recognition (in association with self
major histocompatibility complex (MHC) molecules) and lymphocyte
responses to destroy infected cells and prevent organisms replicating
within cells. Lymphocytes differentiating in the thymus and called T
lymphocytes are mainly of two types (expressing two major forms of
MHC):
 CD4 or T-helper cells - interact with class II MHC molecules, leading
to stimulation of various immunological molecules - eg, B
lymphocytes - to produce antibody. They also produce cytokines
which activate macrophages. They are further classified according to
the cytokines produced as T-helper 1 (activate macrophages - involved
in cytotoxic and delayed hypersensitivity responses) and T-helper 2
(make interleukin-4 and -5 and stimulate B lymphocytes to support
antibody production).
 CD8 or T-suppressor/cytotoxic cells - interact with class I MHC
molecules, leading to a chain of events that destroys host cells infected
by a virus.

Passive immunity
This is achieved by giving immunoglobulins and the protection is
immediate but lasts only a few weeks. There are two types:
 Human normal immunoglobulin (HNIG) from pooled plasma. This
contains antibodies to infections prevalent in the donor population.
 Some of these, such as that for hepatitis A, may be falling, ultimately
affording less protection.
 Specific immunoglobulin for tetanus, varicella-zoster virus, rabies
and hepatitis B. These are derived from pooled serum of convalescent
patients.

Vaccine
A vaccine is a biological preparation that provides active acquired
immunity to a particular infectious disease. A vaccine typically contains
an agent that resembles a disease-causing microorganism and is often
made from weakened or killed forms of the microbe, its toxins, or one of
its surface proteins. The agent stimulates the body's immune system to
recognize the agent as a threat.

Vaccination given during childhood is generally safe. Adverse effects, if

any, are generally mild. The rate of side effects depends on the vaccine
in question. Some common side effects include fever, pain around the
injection site, and muscle aches. Additionally, some individuals may be
allergic to ingredients in the vaccine.

Types
Vaccines contain dead or inactivated organisms or purified products
derived from them.
There are several types of vaccines in use.[33] These represent different
strategies used to try to reduce the risk of illness while retaining the
ability to induce a beneficial immune response.

Inactivated vaccine
Some vaccines contain inactivated, but previously virulent, micro-
organisms that have been destroyed with chemicals, heat, or radiation.
Examples include the polio vaccine, hepatitis A vaccine, rabies
vaccine and some influenza vaccines.
Attenuated vaccine
Some vaccines contain live, attenuated microorganisms. Many of these
are active viruses that have been cultivated under conditions that disable
their virulent properties, or that use closely related but less dangerous
organisms to produce a broad immune response. Although most
attenuated vaccines are viral, some are bacterial in nature. Examples
include the viral diseases yellow fever, measles, mumps, and rubella,
and the bacterial disease typhoid.
The live Mycobacterium tuberculosis vaccine developed by Calmette
and Guérin is not made of a contagious strain but contains a virulently
modified strain called "BCG" used to elicit an immune response to the
vaccine. The live attenuated vaccine containing strain Yersinia pestis EV
is used for plague immunization. Attenuated vaccines have some
advantages and disadvantages. They typically provoke more durable
immunological responses and are the preferred type for healthy adults.
But they may not be safe for use in immunocompromised individuals,
and on rare occasions mutate to a virulent form and cause disease.