powders, granules, tablets, capsules Dr.pptx

Powders, Granules, Tablets
and Capsules
Dr Samia Ghani
M. Phil Pharmaceutics

1. POWDERS
• Definition:
Powders are uniform mixture of dry finally divided drugs or chemicals
that may be intended for internal or external purposes.
OR
Powders are solid dosage form of medicaments which are meant for
internal and external uses.

• Introduction:
They are available in amorphous or crystalline form.
Drugs are prepared in different forms and shapes but many of them are
prepared by using powder in one way or the other.
Powder used as dosage forms may be prepared from:
1. A naturally occurring vegetable drug.
2. A physical admixing of two or more powdered pure chemical agents
present in definite proportions.
3. Powders may contain small proportions of liquids dispersed
thoroughly and uniformly over the solid components of the mixture
or may be composed entirely of solid materials.

• Powders and Particle Size:
• The physiochemical properties of powders are largely dependent
upon the size and surface area of particles.
• The particles of pharmaceutical powders may be very fine (1µ or
less), may be very coarse (10,000µ or 10 mm).
• In order to standardize particle size of a powder, USP employs
descriptive terms depending upon proportion of powder that is
capable of passing through the opening of standardize sieves of
varying dimensions in a specified time period under shaking in
mechanical shaker.

• USP defined powders as:
VERY COARSE: (no.8):All particles pass through this sieve and no
more than 20%through no. 60 sieve.
COARSE: (no.20):All particles pass through this sieve and no more
than 40% throughno.60 sieve.
MODERATELY COARSE: (NO.40):All particles pass through this sieve
and no morethan 40% through a no.80 sieve.
FINE: (no.60):All particles pass through this sieve and no more than
40% through no.100 sieve.
VERY FINE: (no.80):All particles pass through this sieve and no limit as
to greaterfineness.

• Particle size can influence:
• DISSOLUTION RATE: Drug micronization can increase the rate of drug
dissolutionand its bioavailability.
• SUSPENDABILITY: Suspendability of particles intended to remain
same, butuniformly dispersed in a liquid vehicle.
• DISTRIBUTION: Uniform distribution of a drug substance in a powder
mixture form toensure dose-to- dose uniformity.
• NON-GRITTINESS: Lack of grittiness of solid particles in dermal
ointments, creams,ophthalmic preparations.

• Determination of Particle Size:
SIEVING: Particles are passed by series of sieves of known and successively
smallersize by shaking.
LIGHT ENERGY DIFFRACTION: In which particle size is determined by
reduction in light reaching the sensor as the particle, dispersed in a liquid or
gas, passes through the sensing zone.
MICROSCOPY: In which particle size are sized through the use of a grid.
SEDIMENTATION RATE: In which particle size is determined by measuring
terminal settling velocity of particles through a liquid medium.
CASCADE IMPACTION: Particles are separated into various size ranges by
successively increasing velocity of air stream in which they are carried.
LASER HOLOGRAPHY: A pulsed laser is fired through an aerosolized particle
spray and is photographed in 3 dimensions with a holographic camera,
allowing particles to be imaged and sized individually.

• ADVANTAGES OF POWDER:
• Powders are more stable than liquid dosage forms because of
reactions between drug and drug, drug and other substance.
• Rate of dissolution is more than that of capsule , tablets etc
• Rapid dissolution produces high blood levels in shorter time.
• Easy to swallow even in bulk form, when mixed with food or drink.
• Used as a dry lubricant
• As a drying agent
• As adsorbent of bacteria, bacterial toxins, poisons , gases etc
• It is cheap and wastage is minimum

• DISADVANTAGES OF POWDERS:
• Drugs which deteriorate upon exposure to atmospheric conditions
cannot be dispensed properly in powder dosage forms.
• Bitter, nauseating or corrosive drugs cannot be dispensed in powder
form.
• Powders are costly than tablets and capsules, as there preparation is
more time consuming.
• Inaccuracy of dose in bulk powders is another disadvantage.
• Packaging may prove costly.

• CLASSIFICATION OF POWDERS:
ACCORDING TO THE NO. OF ACTIVE INGREDIENTS PRESENT:
1. Simple powders
2. Compound powders
1. SIMPLE POWDERS:
 This dosage form consists of one active ingredient mixed with some inert
substance i.e. lactose, starch.
EXAMPLE:
 Hyoscine hydrobromide powder used as an anti-emetic.
2. COMPOUND POWDERS:
 This dosage form contains more than one active ingredient.
EXAMPLE:
 Compound bismuth powder
 Compound effervescent powder.
 Compound kaolin powder.

• ACCORDING TO MODE OF DISPENSING:
1.Bulk powders.
2.Divided powders.
1. BULK POWDERS:
ACCORDING TO MODE OF DISPENSING:
 These are the types of powders which are not divided into doses before
being handed to the patient.
 Generally less potent drugs are supplied in the form of bulk powders.
 These are packed in bulk containers after preparation with special
directions on the label for mixing, usage and dosage.
 Boric acid and ZnO Powder used as dusting powder for face and neck.
EXAMPLE:
 Rhubarb powder.

2. DIVIDED POWDERS:
• After preparation of powder, it may be divided into individuals units
based upon the dose to be administered at a single time.
• Potent drugs and those drugs that should be administered in
controlled dosage are usually supplied to the patient in divided
powders.
• Each divided portion of powder is placed on a small piece of paper
which is then folded so as to enclose the medication.
EXAMPLE:
• Headache powders
• Laxatives powders
• ORS

PREPARATION OF POWDERS:
• Following are the steps for preparation of powders:
1. SPATULATIONS: Small amounts of powders, having same range of particle
size and densities maybe mixed on a sheet of paper with spatula.
2. TRITURATION: Powders may be mixed in a mortar to attain properties of
lightness and diffusibility.
3. SIFTING: Compound powders containing vegetable substances often
requires sifting to break up the small masses of cohering particles. When
free flowing, light powders are desired, ingredients maybe brushed through
a sieve.
4. TUMBLING: When simple mixing powders is desired without reduction in
particular size. Wide mouthed containers are used, they rotate generally by a
motorized process. Tumbling is recommended for mixing powders with
considerable density difference.

• PACKAGING OF POWDERS:
• Packaging takes place in two ways:
1. DIVIDED POWDER PACKAGING OR UNIT DOSE PACKAGING:
• It is used for potent drugs or for drugs to be used at controlled rate
and dosage.
• Powder after mixing is divided into portion and then wrapped in a
paper to enclose the required amount for single dose.
• These single dose wrappers are then packaged in envelopes or boxes.
• If powder, for divided packaging is, hygroscopic, volatile etc then an
inner wrapper of parchment is necessary.

2. BULK PACKAGING OR MULTIDOSE PACKING:
• This is recommended for less potent drugs.
• Bulk powders are usually sent out in screw capped jars or bottles
with mouth sufficiently wide to take tea spoon as required.
• They may be supplied in the form of aerosols.

2. GRANULES
• Introduction:
• The term Granules is derived from Latin word “Granulum” meaning
little grain, Granules are prepared from powdered substances, the
particles which are made up of powders aggregate with the help of
solvent or binder.
• Definitions:
• Granules are prepared Agglomerates of smaller particles.
• Granules are small particles gathered into a larger, permanent
aggregate in which the original particles can still be identified.

• Shape and Size:
• They are generally irregular shaped and behave as single large particle. They are usually in 4-12 sieve size
range, however granules of various mesh size maybe prepared depending upon the requirements.
• Characteristics:
• Bulk flow characteristics of granular materials do differ from those of homogeneous fluids in several
important ways:
Shearing or shaking a granular material may result in its becoming in homogeneous in space and time.
• Granular materials tend to clog when forced through a constriction.
• A compacted granular material must expand (or dilate) before it can deform.
• Turbulence is almost impossible to achieve in granular materials.
• Granular materials can support (small) shear stresses indefinitely.
• Granular materials are often in homogeneous and anisotropic.
• Granular materials exhibit avalanches.

Types:
Granules can be categorized as follows.
1. Effervescent Granules:
• Effervescent granules are uncoated granules generally containing acid
substances and carbonatesor hydrogen carbonates which react rapidly in
the presence of water to release carbon dioxide. They areintended to be
dissolved or dispersed in water before administration.
2. Coated Granules:
• Coated granules are usually multi-dose preparations and consist of
granules coated with one ormore layers of mixtures of various excipients.
3. Gastro-Resistant Granules:
• Gastro-resistant granules are delayed-release granules that are intended to
resist the gastric fluidand to release the active substance(s) in the intestinal
fluid. These properties are achieved by coveringthe granules with a gastro-
resistant.

4. Modified-Release Granules:
Modified-release granules are coated or uncoated granules which contain special
excipients or which are prepared by special procedures, or both, designed to modify
the rate, the place or the time at which the active substance or substances are
released.
5. Granules Result after Wet Granulation:
• The following types of granules result after wet granulation.
A. Crust Granules:
• A fluid substance is used to as a moistening agent that partially dissolves the contents. A
concentrated solution thus formed, leaves a crust after drying, which is then transformed
into granules.
B. Binder Granules:
Gelatin, starch or similar substance is used as a binder in manufacturing this type of
granules.
C. Sintered Granules:
• When heat is employed to melt the substance during the manufacture process, such
type of granules is called sintered granules.

• Granules Coating:
• Granules may be coated in order to improve the flavor or to modify
the release of drug.
• Procedure:
A.IF SMALL DOSE OF DRUG IS REQUIRED
• Starch granules of (25/20 mesh size) are first coated with an adhesive
material, followed by the powdered drug, and the pellets are dried.
This process is repeated until the desired amount of drug appears on
the granules.

B. IF DOSE OF DRUG IS LARGE:
• The starting material may be drug itself, instead of the starch granules.
• The resultant granules are then subjected to coating with the required material.
• In case of slow release granules some of the granules may remain uncoated, to
provide immediate release,
• Others receive varying coats of lipid material like;
bees wax
carnauba wax
glyceryl-monostearate
Cellulosic material like
Ethylcellulose, or a mixture of both
• Granules of different coating thickness are then obtained and the coating
material maybe coloredin order to distinguish granules of different coating
thickness.

• Desired Release Characteristics:
• The granules of different groups are then blended properly in certain
proportion, to attain the desired release characteristics.
• In case of gastro-resistant or enteric coated formulations, there is a
wide range of choice of materials.
• These materials range from water-resistant films to pH-sensitive
materials.
• Some are digested or emulsified by intestinal juices, and some
slowly swell and fall apart when solvated.
• Many formulations use a combination of these effects to achieve the
desired objective.

• Examples of Materials used for Enteric Coating:
Cellulose Acetate Phthalate (dissolves above pH 6.0)
Acrylate Polymers (pH 6-7)
Hydroxypropyl Methylcellulose Phthalate (pH 5.0-5.5)
Polyvinyl Acetate Phthalate (pH 5.0-5.5)
Sometimes sucrose or other flavoring agent is used to mask the
undesirable taste of a formulation.

• Preparation:
• Following Methods are employed for the preparation of granules:
1. Wet method which is further subdivided into;
i. Simple wet method
ii. Fluid bed processing
2. Dry method which is further subdivided into;
i. Slugging method
ii. Roll compactor method

1. WET METHOD:
i. SIMPLE WET METHOD:
In this method first step is the moistening of powder or powder mixture
which is then passed through a screen of the mesh size for the production of
desired size of granules. The granules are placed on drying trays and dried by
air or under the heat and are periodically moved about on the drying trays
which prevents its adhesion into a large mass or bulk.
ii. FLUID BED PROCESSING:
• In this method particles are vigorously dispersed and suspended in a
conical piece of equipment while a liquid excipient is sprayed on them and
the product on drying form granules or pellets of defined particle size.

2. DRY METHOD:
i. ROLL COMPACTOR METHOD:
The dry powder is passed through a roll compactor &then through a granulation
machine. A roll compactor, also called a Roll Press or Roller Compactor, processes a
fine powder into dense sheets or forms by forcing it through two mechanical
rotating metal rolls running counter to each other. The surface of the compacting
rolls may be smooth or may have pocket indentations or corrugations allowing
compaction of different forms & textures. The compacted powder is granulated to
uniform particle size in a mechanical granulator. Powder compactors are generally
combined in sequence in integrated compactor granulation system.

ii. SLUGGING METHOD:
In this method compression of powder or powder mixture into large
tablet or slugs takes place by a compressing machine under 8000 to
12000 pounds of pressure, depending on the physical characteristics of
the powder.
The slugs are generally flat faced & about 2.5cm (1 inch) in diameter.
The slugs are granulated into the desired particle size, generally for use
in the production of tablets. The dry process often results in production
of fines, which is powder that has not agglomerated into granules.
These fines are separated, collected & reprocessed.

• Advantages of Granules:
i. Easier to handle than powders.
ii. Large doses are difficult to be formulated into tablets, so they can easily
be given in the form of granules.
iii. The chemical and physical stability of granules is more than the mother
powder.
iv. Granules do not become hard mass or cake, on standing as powders do.
v. The surface area of granules is much less than that of powders, so
environmental factors have less deteriorating effect on them.
vi. They get easily dissolved in water as compared to some light and fluffy
powders which usually float on the surface of water.
vii. They possess much better flow properties as compared to powders.
viii. They maybe coated with sugar or other material to mask the undesirable
taste, but this cannot be done with powders.

• Disadvantages of Granules:
i. Packaging of granules requires special care and is less economical
than that of capsules and tablets.
ii. It is difficult for the patient to measure the exact amount of dose to
be taken.
iii. In case to damage to the packing material, the entire product gets
exposed to environment, where as in case of tablets only single
tablet gets exposed.
iv. The drugs liable to hydrolysis cannot be formulated in the form of
granules, which mostly require formation of aqueous solution or
suspension prior to administration.

• EFFERVESCENT GRANULES:
• Definition:
Effervescent Granules or Salts are the coarse or very coarse powders containing a medicinal
agent in a dry mixture composed of sodium bicarbonate, citric acid and tartaric acid.
• Explanation:
When added to water they liberate carbon dioxide due to the reaction of acids and bases.
This is the basic cause of production of effervescence.
The carbonated solution produced due to above reaction masks the saline or undesirable taste
of medicinal agent present.
Citric acid and tartaric acid are used together for ease.
If tartaric acid is used alone as acid then granules produced will lose their firmness and
crumbliness will be the result.
Similarly if citric acid is used alone then results will be a sticky mixture difficult to granulate.

• Methods of Preparation:
• Effervescent Granules are produced by two general methods:-
1. FUSION METHOD:
• In this method, one water molecule in each molecule of citric acid will act
as binding agent for the powder mixture.
• The citric acid crystals are powdered before mixing with other powders.
• Then it is mixed with the other powders of same sieve size to ensure the
uniformity of mixture.
To avoid the effect of acids the sieve and other equipments should be made
of stainless steel or other resistant material. (The mixing of powders is done
rapidly). Similarly to avoid the absorption of moisture and premature
chemical reaction, the mixing is done in an environment of low humidity.
• The powder is placed on a suitable dish in an oven at 34°C to 40°C. In
heating process, an acid-resistant spatula is used to turn the powder.

• The water of crystallization will be released during the heating. So in
the result of this some portion of the powder will be dissolved and
the reaction will set which in turn releases carbon dioxide.
• Due to release of carbon dioxide and the reaction the soft mass of
powder will turn into spongy when it become as bread dough.
• It is removed from the oven and rubbed through sieve of desired size.
A No. 4 sieve produces granules of size large. Similarly a No. 8
produces medium size and No. 10 of small size granules.
• The granules are dried at a temperature of 54°C not more than that.
• It is immediately placed in containers and tightly sealed.

2. WET METHOD:
It is another method of preparation of Effervescent Granules.
• The main difference between wet method and fusion method is that
in wet method the binding agent is water added in the alcohol as the
moistening agent, forming a pliable mass for granulation.
• The liquid is added in portions till a mass like bread dough is formed.
• Then granules are prepared by usual method of granulation through
sieve.

• Significance:
Effervescent Granules have following significances:
i. They have effective effervescence.
ii. In this effective utilization of the acids and bases present.
iii. There is a stable granulation.
iv. They have pleasant tasting.
v. They are efficacious product.

3. TABLET DOSAGE FORM
• Introduction:
Tablets are the most common solid dosage form that is given by Oral
route (GIT).
They are safer than injectables.
Pills are small, round, solid dosage forms containing a medicinal
agent and intended for oraladministration. Nowadays pills have been
replaced by tablets and capsules.
Friable pills were first prepared by Upjohn in the 1950s. Later, pills
were replaced bycompressed tablets.

• Definition:
• Tablets may be defined as « solid dosage pharmaceutical forms containing
drug substances with or without suitable diluents and prepared either by
compression or molding method ».
Tablets are solid dosage forms 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 manufacturing.

• Tablets may be defined as the « solid unit dosage form of medicament or
medicaments with or without suitable diluents and prepared either by
molding or by compression ».
A tablet is a mixture of active substances and excipient, usually in powder
form, pressed or compressed or compacted into a solid.
The excipient include binders, glindants (flow aids)and lubricants to ensure
efficient tableting, disintegrates to ensure that the tablets break up in the
digestive tract; sweetness or flavor to mask the taste of bad-tasting active
ingredients and pigments to make uncoated tablets, visually attractive.

• Properties of Tablets:
i. The properties of tablets are following:
ii. They are different in shape, size and weight which depend upon the
amount of medicament and the mode of administration.
iii. It should be an elegant product having its own identity.
iv. It should have the strength to withstand the rigors of mechanical shocks.
v. It should have the chemical and physical stability to maintain its physical
attributes.
vi. It must be able to release the mechanical agent.
vii. Tablets are disk shaped with convex surfaces but they are also-available
in special shapes like round, oval, oblong, cylindrical, square, triangular
etc.

viii. The weight of oral tablets may range from 0.2 to 0.8 gm including
the diluents but the tablets meant for administration other than oral
route may be lighter or heavier.
ix. They offer a number of advantages to the patient, prescribers,
manufacturer and the manufacturing pharmacist.
Because of these advantages their popularity is continuously
increasing day by day.

• Composition of Tablets:
• It comprises a mixture of active substances and excipients usually in
powder from pressed or compacted from a powder into a solid dose.
• The excipients can include diluents, binders or granulating agents, glidants
(flow enhancers) and lubricants to ensure efficient tableting; disintegrants
to promote tablet break-up in the digestive tract; sweeteners or flavors to
enhance taste; and pigments to make the tablets visually attractive.
• A polymer coating is often applied;
a) To make the tablet smoother and easier to swallow.
b) To control the release rate of the active ingredient
c) To make it more resistant to the environment (extending its shelf life)
d) To enhance the tablet's appearance.

• Properties of Excipients:
i. It should be Inert– shouldn‟t have pharmacological effect.
ii. It should be compatible with API– shouldn‟t later the API.
iii. It should be cheap.
iv. It should be easy to handle.
v. It should be stable and pure.

Selection Criteria of Excipients:
i. It should give proper shape to tablet.
ii. It should have proper weight.
iii. It should have proper hardness.
iv. It should have proper rate of dissolution.
v. It should have proper disintegration.
vi. It should have friability–strength of tablet to withstand with the shock
and abrassion.

• Characteristics of an Ideal Tablet:
1. FREE OF DEFECTS:
• A tablet should be an elegant product having its own identity while being free of
defects such as contamination, chips, cracks and discoloration.
2. PHYSICAL STABILITY:
• A tablet should have the chemical and physical stability to maintain its physical
attributes over time. Various physical properties of tablets can undergo change
under the environment or stress conditions and that physical stability, through its
effects on bioavailability in particular can be of more significance.
3. CHEMICAL STABILITY:
• A tablet should have the chemical and physical stability to maintain its physical
attributes over time so as not to allow alternation of medicinal agents.

4. RELEASE OF MEDICINAL AGENTS:
• The tablet must be able to release the medicinal agents in the body in a
predictable manner and reproducible manner.
5. STRENGTH:
• A tablet should have strength to withstand the rigors of mechanical shocks
encountered in its production, packaging, shipping and dispensing.
6. COLOUR:
• The colour of product must be uniform within a single tablet. Non
uniformity of coloring not only lacks esthetic appeal but could be
associated by the consumer with non- uniformity of content and general
poor quality of product.
7. ODOUR:
• The presences of an odour in a batch of tablets could indicate a stability
problem, such as the characteristics odour of acetic acid in degrading the
aspirin tablets.

• Types and Classes of Tablets:
• There are four major types of tablets. These are following:
1. Tablets ingested orally
2. Tablets used in oral cavity
3. Tablets administered by other routes
4. Tablets used to prepare solutions

1. Tablets Ingested Orally:
Orally ingested tablets are designed to be swallowed intact, with
exception of chewable tablets.
These are further classified as:
I. Compressed tablets
II. Multiple compressed tablets.
I. Compressed Tablets:
• These tablets are swallowed as such. They are placed over the tongue
and swallowed with adrink of water or any other suitable liquid. Most
of them are formulated in such a way that theydisintegrate in the
stomach and dissolve in the gastric fluids thus absorption takes place
from there.

• Compressed tablets are prepared by single compression using tablet
machines. After a quantity of powdered or granulated tableting
material flow into a die, the upper and lower punches of the tablet
machine compress the material under a high pressure (~tons/in2).
This category refers to standard uncoated tablets made by
compression and employing any of three basic methods of
manufacture.
• They include two types of tablets.
i. Direct Compressed Tablets
ii. Wet Granulation Tablets

II. Multiple Compressed Tablets:
• Multiple compressed tablets are prepared by subjecting the fill
material to more than a single compression. This results into two
types of tablets:
i. Layered Tablets
These are the compressed tablets in which the granules of
incompatible substances are compressed into two or more layers
successively in the same tablet. Special tablet making machines are
required for making layered tablets. Layered tablets are prepared by
initial compaction of a portion of fill material in a die followed by
additional fill material and compression to form two-layered or three-
layered tablets, depending on the number of separate fills.

ii. Compression Coated Tablets (Tablet within tablet)
• In preparation of compression coated tablets special machines are required
to place the performed core tablet precisely within the die for application
of surrounding fill material.
Examples include Norgesic Tablet.
• This class is further divided into following subclasses.
These are as follow:
a) Repeat-action tablets
b) Delayed-action and enteric coated tablets
c) Sugar and chocolate coated tablets
d) Film coated tablets
e) Chewable tablets

• ADVANTAGE:
An advantage of multiple compressed tablets is that medicinal agents
are separated to prevent incompatibility, or each layer provides drug
release at a different stage or for coatingpurposes.
• DISADVANTAGE:
It is tedious and expensive process and requires accurate and precise
machinery.

a) Repeat Action tablets:
• The mode of operation of repeat action coated tablets and their limitations
are based onuncontrolled and unpredictable gastric employing.
b) Delayed Action and Enteric Coated Tablets:
• The delayed action and enteric coated dosage form is intended to release a
drug after sometime delay, or after the tablet has passed through one part
of GI tract into another. Ecotrine tablets and caplets are example.
• ADVANTAGES:
Protects drugs that are destroyed in acid medium.
Protects the stomach from drugs that cause irritation to the gastric
mucosa.

c) Sugar and Chocolate Coated Tablets:
• Compressed tablets may be coated with colored or uncolored sugar
layer. This coating is water soluble and quickly dissolves after
swallowing.
• ADVANTAGES:
Sugar coat protects drug from effects of air and humidity.
It provides a barrier to objectionable taste or odor.
Enhances the appearance of compressed tablets and permits of
identifying manufacturer‟s information.
• DISADVANTAGES:
Time and Expertise is required in the coating process
Size and weight is increased (50 %) so shipping cost is also increased.

d) Film-coated Tablets:
• Film-coated tablets are compressed tablets coated with a thin layer of
a polymer capable of forming a skin line film. By its composition, the
coating is designed to rupture and expose the core tablet.
• ADVANTAGE:
These have an advantage over sugar coated tablets that they are
more durable.
less bulky.
less time consuming to apply.

e). Chewable Tablets:
• Chewable tablets are intended to be chewed in the mouth prior to swallowing and are
not intended to be swallowed intact.
• It can easily administer to children. A number of antacid tablets and multivitamin tablets
are prepared as chewable tablets.
For the preparation of chewable tablets mannitol is used as a base.
It is a white crystalline, chemically inert, non hygroscopic, thermo-stable powder and is
as sweet as that of glucose.
It does not have any objectionable effects but since it is expensive so it cannot be used in
tablets of low cost, therefore other substances like sorbitol lactose, chocolate powder,
dextrose and glycine can be substituted in place of mannitol.
i. These tablets should have very acceptable taste and flavor.
ii. They should disintegrate in a short time and produce cool sweet taste.
iii. Chewable tablets can be taken at any place even if water is not available.
iv. These tablets do not require any disintegrating agent to be present in the formulation.
v. The use of gums and other substances which produce hard granules should be
avoided.
vi. The lubricants used should have agreeable taste.

• 2. Tablets Used in Oral Cavity:
• Tablets that are used in oral cavity are further classified in to two types.
These are following:
i. Buccal and Sublingual Tablets
ii. Troches and Lozenges
iii. Dental Cones
i. Buccal and Sublingual Tablets:
• These two classes of tablets are intended to be held in the mouth. These
are flat oval shaped tablets. It is used because some of the drugs destroyed
in gastric mucosa. These tablets contain large proportions of sweetening
agents like mannitol and/or sucrose to impart sweetness.
• ADVANTAGE:
Sublingual tablets are used for drugs that are destroyed by gastric juice
and/or are poorly absorbed from the GI tract.

ii. Troches and Lozenges:
These are two other types of tablets used in the oral cavity, where they
are intended to exert a local effect in the mouth or throat.
These are made by moulding process.
Lozenges tablets should not disintegrate in the oral cavity but should
dissolve slowly in the mouth to produce continuous effect on the
mucous membrane of the throat.
They can be prepared by molding as well as by compression method.
The formulation of lozenges contain no disintegrating agent
The quantity of binding agent is increased so as to induce slow
dissolution.
The formulation must contain sweetening and flavoring agents.

iii. Dental Cones:
• These are relatively minor tablet forms that are designed to be placed
in the empty socket remaining following a tooth extraction.
• Their usual purpose is to prevent the multiplication of bacteria.

• 3. Tablets Administered by Other Routes:
• There are two subclasses of tablets administered by other routes.
i. Implantation Tablets
ii. Vaginal Tablets

i. Implantation Tablets:
Implantation or depot tablets are designed for subcutaneous implantation
in animals or man. Their purpose is to provide prolonged drug action.
These tablets are usually small,cylindrical or rosette-shaped and are
typically not more than 8mm in length.
Since these tablets are to be implanted I/M or S/C therefore they must be
sterile.
They must be prepared under aseptic conditions and packed in unit dose
sterile containers.
No excipients are used and they are compressed under heavy pressure.
These tablets are more commonly used in veterinary medicine than human
medicine.
They can also be used for birth control in human beings.
Generally steroidal hormones like testosterone, stilbesterol etc. are
formulated as implants.

• ii. Vaginal Tablets:
Vaginal tablets or inserts are designed to undergo slow dissolution and
drug release in the vaginal cavity.
The tablets are typically ovoid or pear-shaped to facilitate retention in the
vagina.
This tablet is used to release antibacterial agents, antiseptics or astringents
to vaginal infection.
Some laxative suppositories are also formulated as compressed tablets.
The active medicaments are mixed with such disintegrating agents which
either swell up after absorbing moisture or produce effervescence thus
facilitating disintegration.
These rectal tablets are covered with thin layers of PEG which act as
protective covering and also facilitate the insertion of these tablets into the
rectum.

• 4. Tablets Used to Prepare Solutions:
• Tablets used to prepare solutions are divided into subclasses. These
are as follow:
i. Effervescent Tablets
ii. Dispensing Tablets (DP)
iii. Tablets Triturates (TT)
iv. Hypodermic Tablets (HT)

i. Effervescent Tablets:
These tablets are designed to provide a solution rapidly with the
simultaneous release of carbon dioxide.
The tablets are typically prepared by compressing the active
ingredients with mixtures of organic acids such as citric acid or
tartaric acid.
The most widely produced effervescent tablet is one that contains
Aspirin.
Examples are Alka-Seltzer Original and Zantac EFFER dose.
• ADVANTAGE:
Fast disintegration and dissolution of drug for rapid action
(alkalinizing analgesic tablets).

ii. Dispensing Tablets:
Dispensing tablets are intended to be added to a given volume a
water by the pharmacist orthe consumer, to produce a solution of a
given drug concentration.
Materials that have been commonly incorporated in dispensing
tablets include mild silver proteinate, bichloride of mercury,
merbronium and quaternary ammonium compounds.
Dispensing tablets are less commonly usedor they‟re no longer in
use.
These tablets had the dangerous potential of being inadvertently
dispensed as such to patients.

iii. Tablets Triturates:
Tablets triturates are small, usually cylindrical, molded or compressed
tablets.
These are rarely used tablets.
Generally potent medicaments and highly toxic drugs in small doses are
used for preparing the molded tablets.
They provided an extemporaneous method of preparation.
The potent medicament is diluted with a diluents like Lactose, Dextrose,
The mixed powders are moistened with a suitable dilution of alcohol.
The soft mass so prepared is pressed into perforations of the mold with a
spatula
The excess of the mass is removed by applying pressure over the spatula.
This perforated plate of the mold filled with the mass is placed over
another plate having exactly the same number of projecting pegs as that of
to get a soft mass.

The perforations and these projecting pegs completely fit into the
holes.
A little pressure is applied over top plate which will force the plate
move downward, leaving the molded tablets on the projecting pegs.
The ejected tablets are spread in single layers on clean surface and
dried either by keeping in a warm place or hot air oven.
Now a day‟s tablet triturates may also be prepared on automatic
tablet triturate machines.
A tablet triturate machine can prepare 2500 tablet triturates per
minute.
Pharmacists also employ tablet triturates in compounding.
For example, triturates are inserted in capsules or dissolved in liquid
to provide accurate amounts of potent drug substances.

iv. Hypodermal Tablets:
They were originally used by physicians in extemporaneous preparation of
parental solutions.
These tablets are composed of one or more drugs with other readily water
soluble ingredients are intended to be added to sterile water or water for
injection.
These are less used tablets today.
Hypodermic tablets are soft readily soluble tablets which are made in a tablet
triturate mold.
They are used for preparing solutions to be injected, therefore in selecting the
materials used for preparing the hypodermic tablets care must be taken that they
should be completely and readily soluble and no insoluble particle should be
present.
They should be free from bacterial contamination and proper precautions should
be taken during molding regarding contamination and cleanliness.
Since the solutions prepared from hypodermic tablets are rarely sterile and a
number of sterile parenteral solutions are now available therefore the use of
hypodermic tablets for preparing solution for injections is being discouraged.
They are no longer used.

Methods to Prepare Tablets:
• There are four methods to prepare tablets. These are as follow:
1) Direct Compression Method
2) Wet Granulation Method
3) Dry Granulation Method
4) Fluid Bed Granulation Method

1) Direct Compression Method:
Some granular chemicals, like potassium chloride, possess free-flowing
and cohesiveproperties that enable them to be compressed directly in
a tablet machine without any need of granulation.
For chemicals lacking this quality, special pharmaceutical excipients
may be used to impart the necessary qualities for the production of
tablets by direct compression.

These excipients include:
i) fillers, such as;
Spray-dried lactose
Micro-crystals of alpha-monohydrate lactose
Sucrose–invert sugar–corn starch mixtures,
Microcrystalline cellulose
Crystalline maltose
Dicalcium phosphate
ii) Disintegrating agents, such as direct compression starch, sodium
carboxymethyl starch, cross-linked carboxymethylcellulose fibers, and cross-
linked polyvinylpyrrolidone;
iii) lubricants, such as magnesium stearate and talcoGlidants, such as fumed
silicon dioxide.

iv) Binders include such as:
Carboxymethyl cellulose, sodium cellulose, microcrystalline, starchoAgar, acacia
gum, glucose.
The capping, splitting, or laminating of tablets is sometimes related to air
entrapment during direct compression.
When air is trapped, the resulting tablets expand when the pressure of tableting is
released, resulting in splits or layers in the tablets.
Forced or induced feeders can reduce air entrapment, making the fill powder more
dense and amenable to compaction.
v) Lubricants are used to:
Improve the flow of granules in the hopper to the die cavity.
Prevent sticking of tablet formulation to the punches and dies during formulation
Reduce the friction between the tablet and the die wall during the tablet’s
ejection from the tablet machine.
Give sheen to the finished tablets.

2) Wet Granulation Method:
Wet granulation is a widely employed method for the production of
compressed tablets.
The steps required are
a) Weighing and blending the ingredients
b) Preparing a dampened powder or a damp mass
c) Screening the dampened powder or damp mass into pellets or granules
d) Drying the granules
e) Sizing the granulation by dry screening
f) Adding lubricant and blending
g) Forming tablets by compression

3) Dry Granulation Method:
By the dry granulation method, the powder mixture is compacted in
large pieces and subsequently broken down or sized into granules.
For this method, either the active ingredient or the diluent must have
cohesive properties. Dry granulation is especially applicable to
materials that cannot be prepared by wet granulation because they
degrade in moisture or the elevated temperatures required for drying
the granules.
• Two process invovle in dry granulation method thar are:
A. Slugging
B. Roller Compactation

A. Slugging:
• After weighing and mixing the ingredients, the powder mixture is
slugged, or compressed into large flat tablets or pellets about 1 inch
in diameter.
• The slugs are broken up by hand or by a mill and passed through a
screen of desired mesh for sizing.
• Lubricant is added in the usual manner and tablets are prepared by
compression.
• Aspirin, which is hydrolyzed on exposure to moisture, may be
prepared into tablets after slugging.

B. Roller Compactation:
• Instead of slugging, powder compactors may be used to increase the
density of a powder bypressing it between rollers at 1 to 6 tons of
pressure.
• The compacted material is broken up, sized and lubricated and tablets
are prepared by compression in the usual manner.
• The roller compaction method is often preferred to slugging.
• Binding agents used in roller compaction formulations include
methylcellulose or hydroxyl methylcellulose (6% to 12%), which can
produce good tablet hardness and friability.

• ADVANTAGES
a. May produce up to thousand of tablets per minute
b. Double rotary presses produce 2 tablets for each die.
• DISADVANTAGES
a. Lamination (horizontal striations) occur due to high speed.
b. Capping, in which top of the tablet separates from the whole
because fill material does not have enough time to bond after
compression.

4. Fluid Bed Granulation Method:
Technologic advances now allow the entire process of granulation to be
completed in a continuous fluid bed process, using a single piece of
equipment, the fluid bed granulator.
This is the latest method of preparation of tablet.

Process after Preparation:
• After preparation of tablets, tablets undergoes following processes:
i) Tablet Dedusting:
• To remove traces of loose powder adhering to tablets following
compression, the tablets are conveyed directly from the tableting machine
to a deduster. The compressed tablets may then be coated.
ii) Tablet Coating:
• Tablets are coated for a number of reasons, including to protect the
medicinal agent against destructive exposure to air and/or humidity; to
mask the taste of the drug; to provide special characteristics of drug
release (e.g., enteric coatings); and to provide aesthetics or distinction to
the product.

iii) Waterproofing and Sealing Coats:
• For tablets containing components that may be adversely affected by
moisture, one or more coats of a waterproofing substance, such as
pharmaceutical shellac or a polymer, are applied to the compressed
tablets before the sub-coating application. The waterproofing
solution (usuallyalcoholic) is gently poured or sprayed on the
compressed tablets rotating in the coating pans. Warm air is blown
into the pan during the coating to hasten the drying and to prevent
tablets from sticking together.

iv) Sub-coating:
• After the tablets are waterproofed if needed, three to five subcoats of
sugar-based syrup are applied. This bonds the sugar coating to the
tablet and provides rounding. The sucrose and water syrup also
contains gelatin, acacia, or PVP to enhance coating. When the tablets
are partially dry, they are sprinkled with a dusting powder, usually a
mixture of powdered sugar and starch but sometimes talc, acacia, or
precipitated chalk as well.

v) Smoothing and Final Rounding:
• After the tablets are subcoated, 5 to 10 additional coatings of thick
syrup are applied to complete the rounding and smooth the coatings.
This syrup is sucrose based, with or without additional components
such as starch and calcium carbonate. As the syrup is applied, the
operator moves his or her hand through the rolling tablets to
distribute the syrup and to prevent the tablets from sticking to one
another. A dusting powder is often used between syrup applications.
Warm air is applied to hasten the drying time of each coat.

vi) Finishing and Colouring:
• To attain final smoothness and the appropriate color to the tablets, several
coats of thin syrup containing the desired colorant are applied in the usual
manner. This step is performed in a clean pan, free from previous coating
materials.
vii) Imprinting:
• Solid dosage forms may be passed through a special imprinting machine to
impart identification codes and other distinctive symbols. Technically, the
imprint may be debossed, embossed, engraved, or printed on the surface
with ink. Debossed means imprinted with a markbelow the surface;
embossed means imprinted with a mark rose above the surface; and
engraved means imprinted with a code that is cut into the surface during
production.

viii) Polishing:
• Coated tablets may be polished in several ways. Special drum-shaped
pans or ordinary coating pans lined with canvas or other cloth
impregnated with carnauba wax and/or beeswax may be used to
polish tablets as they tumble in the pan. Or, pieces of wax may be
placed in a polishing pan and the tablets allowed tumbling over the
wax until the desired sheen is attained. A third method is light
spraying of the tablets with wax dissolved in a non-aqueous solvent.
ix) Packing process:
• At the end of all above, packing of tablets has done with packing
machine and tablets are available in market.

Problems Associated in the Manufacturing of Tablets:
There are two major problems associated in the manufacturing of
tablets.
1. In-process Manufacturing Issues
2. Post Manufacturing Issues

1. in-process Manufacturing Issues:
These problems occurred during manufacturing of tablets. There are
following problems occurred during manufacturing of tablets:
i. Capping and Lamination:
 Capping is a term used to describe the partial and the complete
separation of the top or bottom crowns of tablet from main body of
tablet.
 Lamination is the separation of the tablet into two or more distinct
layers. Capping and lamination encountered in direct compression.

ii. Picking and Sticking:
 Picking is a term used to describe the surface material from a tablet sticking to and being
removed from tablet‟s surface.
 In some cases, colloidal silica is added to formula acts as polishing agent and makes the
punch faces smooth.
iii. Mottling:
 Mottling is an unequal distribution of color on the tablet, with light or dark areas standing
out in otherwise uniform surface.
 One cause of mottling is a drug whose color differs from tablet excipients or a drug
whose degradation products are colored.

• iv. Punch Variation:
Thousandths of an inch the fill in each die varies because the fill is
volumetric.
• v. Hardness Variation:
Hardness variation may occur due to personal or mechanical error.
• vi. Double Impression:
This problem involves only punches that have monogram or other engraving
on them. At the moment of compression, the tablet receives imprint of the
tablet.

2. Post Manufacturing Issues:
These are the problems occurred after manufacturing of tablets.
One of the basic problem occurred during transportation of the tablets.
In process of transportation, tablets broken down that is called
Friability.
This cause the loss of therapeutic efficacy of the tablets.
Others are disintegration and dissolution problems.

• Quality Control Tests of Tablets:
There are two major types of quality control tests of tablets and these are as
follow:
1. Official Tests
2. Non-official TestsOfficial Tests
These tests include
i. Disintegration Tests
ii. Dissolution Tests
iii. Friability Tests

2. Non Official Tests:
These tests include
i. Weight Variation
ii. Thickness of Tablets
iii. Hardness of Tablets
iv. Diameter of Tablets

Advantages of Tablets:
i. They are easy to carry.
ii. They are easy to swallow.
iii. They are attractive in appearance.
iv. Unpleasant taste can be masked by sugar coating.
v. They do not require any measurement of dose i.e. their dose is accurate.
vi. The strip or blister packing has further facilitated the process of taking
the dose by the patient.
vii. Moreover it provides a sealed covering which protects the tablets from
atmospheric conditions like air, moisture and light etc.
viii. Some of the tablets are divided into halves and quarters by drawing lines
during manufacturing to facilitate breakage whenever a fractional dose
is required.
ix. An accurate amount of medicament even if very small amount can be
incorporated.
x. Tablets provide prolonged stability to medicament.

xi. Identification of the products of the tablets is potentially the simplest
and cheapest, requiring no addition process.
xii. Swallowing of the tablets is very easy especially when intake of tablet is
through any suitable liquid, like water.
xiii. Handling of the solid dosage form i.e. tablet is very easy. No special
prevention or precautionary measures are required for handling the
tablets.
xiv. The chances of microbial or bacterial attack are very less for dry, solid
dosage form i.e. tablet as compared to syrups.
xv. Tablets are better suited to large scale production than other unit oral
forms.
xvi. Tablets are one of those oral, solid dosage forms to whom coating can
be applied to improve palatability or reduce the incidence of gastric
irritation.

Disadvantages of Tablets:
i. Irritant effects on the GI mucosa by some solids (e.g., aspirin)
ii. Possibility of bioavailability problems resulting from slow disintegration
and dissolution
iii. Some patients, particularly the children and seriously ill, may experience
difficulty in swallowing tablets. (If the tablet is too large, reformulation
as two smaller units eachcontaining half the required dose, may
minimize the problem in some case)
iv. One of the disadvantages of tablets is that demulcent action of linctuses
can not be effectively obtained with a tablet.
v. Drugs with poor wetting, low dissolution and optimum absorption high
in the gastrointestinal tract may be difficult to formulate as a tablet that
will provide adequate or fueldrug bioavailability.
vi. Bitter tasting drugs, drugs with an objectionable odour, or drugs that are
sensitive to oxygen or atmospheric moisture may require capsulation
prior to compression or tablets may require coating.

4. CAPSULES DOSAGE FORM
• Definition:
Encapsulation refers to a range of techniques used to enclose
medicines in a relatively stableshell known as a capsule.
Capsules are dosage form containing unit doses of drugs enclosed in a
soluble shell of gelatin,starch or similar material and intended to be
swallowed whole orally.

• Introduction:
• Capsules equal the tablets in their popularity and usage.
• They are convenient means of dispensing a variety of solids, semi-solids
and liquids.
• All capsules basically consist of soluble shells of a material like gelatin. The
solid substances are dispensed in hard capsules for dispensation of liquids
and semi-solids soft capsules are preferred.
• Capsules are generally employed for enclosing materials meant for oral
administration and are swallowed as a whole.

• Nowadays some capsules are administered through rectum or vagina
and are useful substitutes for the more conventional types of
suppositories based on oleaginous or water soluble bases.
• Soft capsules can also be employed for enclosing single application of
eye ointments. Here the capsules have to be pricked with needle and
the contained ointment transferred to ophthalmic cavity by
application of slight pressure.
• Capsules afford a tasteless, odorless enclosure, convenient for
administration of variety of medicaments, which are otherwise
difficult to administer.
• However, aqueous or hydro-alcoholic liquids cannot be enclosed in
capsules because they dissolve gelatin.

Danger:
• Capsules should not be used for packaging of highly water soluble
materials such as ammonium chloride, potassium bromide, potassium
chloride etc., because sudden release of such compounds can cause
irritation.
• It is also not advisable to use capsules for very deliquescent (to become
liquid) or efflorescent (loss of water of hydration) materials. Deliquescent
substances may draw up moisture from the capsule shell rendering it
brittle. The efflorescent materials may cause softening of the capsules.

Types of Capsule:
There are two types of capsules available
1. Hard Gelatin Capsules
2. Soft Gelatin Capsules

1. HARD GELATIN CAPSULE
This type is also referred as the dry filled capsule, which consists of two
sections, one slipping over the other, thus completely surrounding the
drug formulation.
These are formed from gelatin containing sugar and water in
appropriate proportions.
Hard gelatin capsules are manufactured in two sections:-
The capsule body
Shorter cap
The two parts overlap when joined, with the cap fitting snugly-over
opened capsule body.

Types of Hard Gelatin Capsules:
Hard gelatin capsules are of following types:
Snap Fit
Coni Snap
Coni Snap Supro
• All these types have locking grooves, generally, two, Snap Fit Capsules
are bearing the disadvantage of slitting and denting due to contact
b/c the rim of capsule body is straight.

• Capsule Shell:
• The shell of hard gelatin capsules basically consists of gelatin, plasticizers
and water.
• Modernday shells may, in addition, consist of preservatives, colours,
opacifying agents, flavours, sugars, acids, enteric materials etc. The gelatin
is marketed in a large number of varieties and a specific quality and gelatin
having specified gel strength, viscosity, iron content etc. should be selected
for capsules.
• The variations in gelatin properties arise because of changes in molecular
weights and methods followed in conversion into gelatin.
• The average molecular weight of gelatin varies between 20,000 and 2,
00,000.
• Two popular grades of gelatin, Pharmagel-A and Pharmagel-B, are acid
processed and alkali processed respectively
• For capsule shells generally a mixture derived from pork skin and bones is
used.
• Pork skin gelatin contributes plasticity while bone gelatin gives firmness.
However, in using bone gelatin its calcium phosphate content should be
watched since undue amounts can make capsules hazy.

• One important reason for the exclusive use of gelatin for making hard
and soft capsules is its solubility characteristics in stomach fluids. It
absorbs cold water readily, though the rate of absorption depends
upon moisture content of gelatin.
• The plasticizers used are glycerin, sorbitol etc. The exact proportions
of gelatin and plasticizers have to be determined on the basis of the
use of capsules and their storage conditions.
• Preservatives, if included, are generally a mixture of methyl-paraben
(4 parts) and propylparaben (1 part) to the extent of 0.2%.

• Flavors, if added, should not exceed 2% and are generally ethyl-vanillin or
essential oils.
• Sugar, if included, may be up to 5% to give the gelatin shell desirable chewable
characteristics.
• Manufacturing summary:
• The capsule shells are nowadays produced on mass scale by sophisticated
machinery. Fundamentally speaking, in every machinery, pairs of pins
corresponding to the bodies and the caps of the capsules are dipped in heated
gelatin solutions containing the necessary additives. The dipping is followed by
withdrawal of pins and their rotation a few times to distribute the solutions
evenly. Cold air is simultaneously blown on the rotating pins to firm up the gelatin
shells. These pins are, there after, passed though series of kilns with controlled
rates of drying. After drying, the bodies and caps are removed from pins by
mechanical jaws and are trimmed to appropriate lengths by rotating blades.
Finally the caps are placed on the bodies.

• Storage:
• The capsules shells should be stored under controlled conditions of
temperature and humidity. The normal moisture content of shell is 10 to
15%. Under conditions of low humidity they may soften and grow tacky.
• Sizing:
In Canada, starch or cellulose are available in a range of sizes with
designations 000, 00, 0E, 0,1, 2, 3, and 4. The respective volumetric
capacities are 1.37ml, 950μl, 770μl, 680μl, 480μl,360μl, 270μl, and 200μl.
The shells for human use are marketed in 8 sizes depends upon its density
and compressibility.
Normally the shell manufacturers give a guidance of the approximate
quantities of selected drugs that can be contained in different sizes.
For instance, data from Parke Davis&Co. with respect to Aspirin is
reproduced below:
For veterinary use larger capsules Nos. 10, 11 and 12 approximating to
capacities of 30, 15 and 7.5 gms. Are also marketed.

1.Hard Gelatin Capsules for Human Use:
Hard gelatin capsules intended for human are manufactured in eight
sizes.
000 _______ 1000mg
00 ________ 650mg
0 _________ 520mg
1 _________ 320mg
2 _________ 260mg
3 _________ 195mg
4 _________ 160mg
5 _________ 97mg

• Manufacture:
Some special techniques used in hard gelatin capsule manufacturing
are:
I. Imprinting (a word or company name)
II. Sealing or banding (tamper proofing)
III. Two-phase filling (to separate incompatible material in same
capsule)
IV. Various coating etc.

• HARD GELATIN CAPSULE MANFACTURING STEPS
i. Before capsule manufacturing start, first all raw materials should be
released by Quality Control and all equipment should be validated.
ii. First step is make gelatin solution25-30%: gelatin and hot demineralized
water are mixed under vacuum in Gelatin Melting System.
iii. After aging in stainless steel receiving tanks, the gelatin solution is
transferred to stainless steel feed tanks.
iv. Dyes, opacifants, preservative and any needed water are added to the
gelatin in the feed tanks.
v. The feed tanks are then used to gravity-feed gelatin into the machine for
making capsules.

vi. Dipping: At the end of machine is a hopper called a dip pan or pot. This holds a
fixed quantity of gelatin at constant temperature between 45 to 55 C. capsules
are formed by dipping the sets of molds which are at the room temperature,
22 degree C into this solution.
vii. Spinning: The molds are slowly withdrawn from solution and then rotated
during their transfer to upper level of the machine in order to form a film of
uniform thickness.
viii. Drying: Groups of pin bars are then passed through a series of drying kilns in
which large volume of controlled humidity air are blown over them. When
they reach the rear of machine the bars are transferred back to the lower level
and pass through the further drying kilns.
ix. Cutting and joining: In the front of machine the dried films are removed from
mold, cut to correct length. The two parts are joined together and the
complete capsule delivered from the machine.
x. Output: The output per machine is about 1 million capsules per day,
depending upon the size the smaller the capsule the higher the output.

xi. Assembling: The assembled capsules are not fully closed at this
stage and are in a pre-locked position which prevent them from
falling apart before they reach the filling machine.

• Materials to be filled:
• The materials to be filled in the hard capsules may need formulation
to a certain extent and the following additives may have to be
incorporated:
1. DILUENTS
The dose of a particular medicament may be enough to fill in a suitable
size of the capsule. But there may also be occasions when it is too small
in bulk falling far short of the quantity needed for smallest available
capsule size.
In such instances one or the other diluents has to be added to bring the
medicament up to a desired bulk. The usual diluents selected are
lactose, mannitol, sorbitol, starch etc. The quantities of diluents are
related to the dose of the medicament and the capsule size.

2. PROTECTIVE SORBENTS
In some cases inclusion of inert materials may be called for to physically
separate incompatible or eutectic substances. Sometimes some inert
materials are included to prevent absorption of moisture by
hygroscopic substances. Materials like oxides and carbonates of
magnesium or calcium are suitable for these purposes.
3. GLIDANTS
Glidants become essential when the powders are filled by sautomated
machinery requiring the irregular flow into the capsule bodies many
materials by themselves lack the desired degree of flow and hence
glidants like talcum, stearates etc. are included in suitable amounts.

4. ANTI-DUSTING COMPOUNDS
• In large scale filling operations dust is a real problem and if allowed to go unchecked, can
posses serious health hazards for the workers.
• Presence of potent drugs in the dust can cause its continuous inhalation. Hence, material
to be filled in the capsules should include some anti-dusting components like inert edible
oils. The quantities of oils have to be carefully worked out since excessive amounts can
cause the particles to cohese together.
• Although normally only powders are filled but on occasions fixed oils and other liquids,
that do not permeate through gelatin wall, can be filled in the hard capsules.
• Filling of liquids is done by the use of calibrated droppers or pipettes.
• The other materials to be filled in could be plastic dough like masses rolled into uniform
pipes.
• Before filling pipes are cut into uniform pieces and put in the capsules.
• Sometimes potent drugs are filled in the form of small tablets or pellets and are then
covered with inert materials to fill the body.
• Granular materials can also be conveniently filled in the capsules.

• Substances which are highly soluble in water like citric acid, sodium chloride and
ammonium compounds should not be filled in gelatin capsules since they may affect the
gelatin shell owing to abstraction of water from it.
• Some water soluble substances may also migrate into the gelatin shell thus reducing
potency of the encapsulated substance.
• Excellent examples were thiamine HCl and ascorbic acid. Sometimes even poorly water
soluble substances like benzocaine migrate into the shell.
xii. FILLING
• Extemporaneous filling of a small number of capsules is possible by spreading the
powder to be filled in on a tile or a sheet of paper and pressing the body of capsule on to
it until it is full. Cap is inserted on the body and the capsule weighed against a tare of
empty capsule to get a feel about the drug amount. It may be necessary to fill in some
more or tap out some filled in material in case of variations in weights beyond permitted
limits. On an industrial scale semi automatic or fully automatic equipmentis used for
filling. In these operations the caps are removed, bodies filled, caps replaced and filled
capsules ejected. Some machines can fill 15000 to 20000 capsules per hour.

xiii. FINISHING
• The filled and sealed capsules necessitate a finishing operation before
inspection, bottling or packing in strips/blisters and labeling.
• The following steps are involved in the finishing process:
SALT POLISHING
• In salt polishing, the capsules are rotated in a coating pan type device along
with sodium chloride granules. Later the capsules and granules are
separated by screening on a suitable device. Such a polishing removes
adhering materials from the surfaces of capsules. However, salt polishing
should be done before imprinting, if any, since imprinting may be affected
by salt.
CLOTH DUSTING
• In this process individual capsules are rubbed with cloth which may or may
not contain inert oil. This removes some remaining materials and also
imparts improved gloss.

BRUSHING
• In brushing capsules are projected under a soft rotating brush which removes all remaining dust.
This operation must be supplemented by exposure of capsules to regulated vacuum.
INSPECTION
• This process is desirable to pick up imperfect and damaged capsules manually or with automated
inspecting systems.
SEALING AND LOCKING
• Sealing and locking devices invented by various manufacturers as their novelties are basically
guards against separation of the caps from the bodies during handling, transport etc. However,
incidentally these devices do not permit any tampering of their contents ruling out foul play.
Sealing ofthe caps on to bodies is possible by moistening the upper part of the body and slipping
the cap on. However, many manufacturers seal capsules by means of a colored band of gelatin
placed at the junction of the body and the cap. More recently some configurations have been
developed in the bodies and caps which enable their mechanical locking.
• For instance, Snap Fit capsules, marketed by Parke Davis, have matching interlocking rings on the
body and in the cap. Another method suggested is to bring a hot needle like structure against the
cap where it overlies the body to form a sort of spot weld.

• Some Modern Uses of Hard Gelatin Capsules:
i. Traditionally hard gelatin capsules have been used for enclosure of
powders or other solid substances like granules and pellets.
ii. Recently pastes and oils have also been filled in hard gelatin
capsules.
iii. To prevent leakage of oily materials either thixotropic substances
can be added or the cap and body joints banded with molten
gelatin or sealed with lacquers.
iv. Incompatible drugs also can be usefully supplied in capsules.
v. Multilayer tablets are devices towards this end. But it would be
more useful to make small tablets from each individual drug and
encapsulate them all in one capsule.

vi. Hard gelatin capsules have also been used for drug delivery in
bronchial tract. (To release the drug the capsule is punctured
thereby releasing a fine powder mist which isinhaled into the lungs
along with the breath). Maybe with passage of time some new
applications are developed.

2. SOFT GELATIN CAPSULES
• “The soft gelatin is a soft, globular, gelatin shell some what thicker
than that of hard gelatin capsules. The gelatin plasticized by the
addition of glycerin and sorbitol”
• These are prepared from gelatin to which glycerin or a polyhydric
alcohol such as sorbitol has been added to render the gelatin elastic
or plastic like.

• Introduction:
• Although soft gelatin capsules are nearly a century and a half old, their
increased and varied use is a recent phenomenon.
• As discussed earlier, these capsules can not only be used for packaging of
liquid/semisolid dosage forms, powders etc. but have also been used as
substitutes for suppositories and for containing ear, eye, nose and throat
formulations.
• Suggestions have also been made for packaging cosmetics and foods in soft
gelatin capsules.
• Their popularity is on the increase.
• Besides being elegant the capsules are hermetically sealed and are suitable
for drugs liable to volatilization and atmospheric deterioration.

• Composition:
• The composition of soft gelatin capsule shells is similar to the hard gelatin
capsules except that alarger proportion of plasticizer is incorporated to
make them soft and elastic.
• Shapes:
• These capsules are available in a variety of shapes.
• Spherical
• Round
• Oval
• Oblong
• Elliptical
• Tube shape
• Size wise also the range is bigger and capsules of capacities ranging from 0.1 ml to 30
ml areused.

• Manufacture:
• They are not easily prepared except on a large scale with specialized
equipments
i. Plate process
ii. Rotary die process
iii. Reciprocating die process
iv. Accogel machine
• Soft gelatin capsules are usually prepared, filled and sealed in a
continuous process using special equipment.
• Empty soft gelatin capsules may be prepared and hermetically sealed
for filling at a later time.

i. PLATE PROCESS:
 Soft gelatin capsules may be prepared by plate process using a set of
mold to form the capsules.
 By the plate process A warm sheet of plain or colored gelatin is
placed on the bottom plate of the mold and the medication containing
liquid is evenly poured on it.
 Then a second sheet of gelatin is carefully placed on the top of
medication and the top plate of mold is put into the place.
 Pressure is than applied to the mold to form, fill and seal the capsules
simultaneously.
 The capsules are removed and washed with a solvent harmless to the
capsules.

ii. ROTARY DIE PROCESS:
• Most soft gelatin capsules are prepared by rotary die process, a method
developed in 1933 by Robert P. Scherer.
• Bythis method:
a. Liquid gelatin flowing from an overhead tank is formed into two
continuous ribbons by the rotary die machine and brought together
between twin rotatory dies.
b. At the same time, metered fill material is injected between the ribbons
precisely at the moment that dies form pockets of gelatin ribbons.
c. These pockets of fill containing gelatin are sealed by pressure and heat
and then severed from the ribbons.
d. Use of ribbons of two different colors result in bi-colored capsules.

iii. RECIPROCATING DIE PROCESS
• This process is similar to the rotary process in that ribbons of gelatin are
formed used to encapsulate the fill, but it differs in the actual encapsulating
process.
• The gelatin ribbons are fed between a set of vertical dies that continuously
open and close to form rows of pockets in gelatin ribbons.
• These pockets are filled with the medication and are sealed, shaped and cut
out of the film as they progress through the machinery.
• As the capsules are cut from the ribbons, they fall into refrigerated tanks that
prevent the capsule from adhering to one another.

• Materials to be filled:
They may be employed to contain:
• Liquids
• Suspensions
• Pasty materials
• Dry powders
Soft gelatin capsules are especially important to contain:-
• Drug solutions
• Liquid drugs

• As stated earlier, it is possible to fill liquids, semi-solids as well as
solids into soft gelatin capsules.
• The liquids that are packaged are generally of the following kinds:
Vegetable or aromatic oils, hydrocarbons, ethers, esters, alcohols and
organic acids which are water immiscible;
Polyethylene glycols and non-ionic surfactants which are water
miscible;
Water miscible and relatively non-volatile compounds such as
glycerin, propylene glycol (up to 5-10% of total liquid), isopropyl
glycol etc.

• Conditions for Filling:
• The liquid combinations for encapsulation in soft gelatin capsules must be
able to flow by gravity at about 350 degree C or less.
• In general, liquids ranging in viscosity from 0.2 to 3000 cps. At 250C, can be
encapsulated without any difficulty, except in few cases like glycerin, where
due to lack of tack, the blinding of slide valves and pumps may be caused.
• The liquids to be filled in soft capsules generally call for no formulation and
can be right away filled.
• Liquids which cannot be capsulated thus are water (more than 5%),
alcohols, ketones, acids, amines, esters etc. which can leak through the
capsule shell.
• Liquids with pH below 2.5 or above 7.5 should also be avoided since acidic
liquids cause hydrolysis of the shell and alkaline ones cause tanning
affecting solubility characteristics of the shells.

• The same criteria holds good for solutions as well.
• The soft gelatin capsules these days are being increasingly used for
encapsulation of suspensions of solids in suitable bases.
• The important requirement that a suspension should necessarily meet is
that it must have flow properties similar to liquids and the suspended
solids remain uniformly suspended during the filling operation to ensure
homogeneity of the encapsulated mix.
• To achieve this liquid bases should be carefully chosen. The common
materials cited in literature for this purpose are admixtures of vegetable
oils and non-ionic surfactants, carbowax 400 etc.
• These bases could be used for oral as well as topical dosage forms. For
veterinary dosage forms aliphatic or aromatic hydrocarbons and
chlorinated hydrocarbons can be chose alone or in combination with the
above mentioned materials.

• Applications:
• Soft gelatin capsules are useful when it is desirable to seat medication within
the capsule.
• Soft gelatin capsules are handsome and are easily swallowed by the patient.
• Examples of drugs dispensed in soft gelatin capsule are:-
 Vitamin
 Digoxin
 Demectocycline HCL etc.

• PHYSICAL STABILITY OF CAPSULES
In the use of capsules one important aspect to be remembered is the
physical stability of the capsule shells under varying storage
conditions.
In hard capsules excessive or low humidity conditions must be
avoided as the former tend to soften and the later can make the
capsules brittle. The soft gelatin capsule rapidly attains equilibrium
with the environmental conditions.
However, the nature of these product encapsulated may have an
effect on the capsule shell calling for setting up of physical standards
for each product.
A control capsule, containing mineral oil with a gelatin shell having a
ratio of dry glycerin: dry gelatin between 0.5 to 1 and water to dry
gelatin ratio of 1:1 dried to equilibrium at 20 to 30% relative humidity
at 70 to 800 F is used as standard.

• This capsule unprotected by any other method will be only transiently effected by
humidities lower than 20% R.H. or temperatures ranging from less than 30F to more than
100F.
• As soon as extremes of conditions are removed the capsules return to normal form. High
humidities of more than 60% RH at 70 to 75F can have lasting effects making the
capsulesbloated or softer and tackier. The capsules may also get stuck together and it
may be difficult to separate them.
• Increase in temperature beyond 750F along with high humidities (>45% RH) may fuse the
capsules. Capsules containing water soluble liquids are damaged t greater extents than
the ones having oleaginous products. It is better to expose newly developed capsules
with or without products packed in them to accelerated tests like exposure to 80% RH at
room temperature andto 104 degree F temperatures, in open as well as closed
containers, and observe for 15 days. Such tests give a fair idea of likely behaviour under
storage conditions that capsules may have to face.
• Manufacturers generally pack capsules in devices/containers designed to prevent
exposure to excessive humidity conditions and advise storage within certain temperature
ranges only.

• Advantages of Capsules:
i. Capsules may be used for dispensing solid, semisolid and liquid drugs
ii. Avoidance of the contact with the unpleasant odour and flavor of
medicines
iii. Easy to swallow
iv. Disintegration is both satisfactory and reliable
v. Attractive dosage form
vi. Shells can be colored to give protection from light
vii. Shells are physiologically inert and are easily and quickly digested in GIT
viii. Less adjuncts are necessary than for tablets
ix. If properly stored, the shells contain 12-15% of moisture which gives
flexibility and consequently very considerable resistance to mechanical
stresses

• Disadvantages of Capsules:
i. Capsules are expensive than tablets
ii. They cannot be used for aqueous or alcoholic solutions as they will
attack the shell
iii. Salts which are very readily soluble should not be capsulated as
their sudden release will cause the irritation
iv. Deliquescent or hygroscopic substances cannot be capsulated
v. Insoluble substances such as some bismuth salts are reported to
cause formation of enteroliths in the intestine when administered
in the form of capsules

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