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.
Depending upon their formulation, the gelatin
capsule shells may be hard or soft.
Hard Gelatin Capsules
The hard gelatin
capsule consists of a
base or body and a
shorter cap, which fits
firmly over the base of
the capsule.
Hard Gelatin Capsules
Advantage of Hard gelatin capsules

1. Mask the unpleasant tastes of a drug.

2. Allow powders to be dispensed in an uncompressed
form, thus allowing for quicker dissolution and
absorption of the drug following oral dosing
3. Have the flexibility which permit a wide prescribing
opportunity by the physician in that the pharmacist
may prepare capsules containing a single chemical
substance or a combination of drugs at the
accurate dosage level for the individual patient.
4. Be easier than tablets for some people to swallow.
5. Can alter the release rate of the drug.
Disadvantages or limitations include the
following:

1. They are subject to the effects of relative humidity

and to microbial contamination.
2. They may be difficult for some people to swallow.
3. More expensive (commercially).
 The basic empty capsule
shells are made from a mixture of
gelatin, sugar, and water and are
clear, colorless, and essentially
tasteless.
Colorants may be used to prepare

distinctive
Opaque capsules.
capsules may be prepared by adding an
insoluble substance as titanium dioxide to the gelatin
mixture. Colored, opaque capsules may be prepared
by using both a colorant and the opaque-producing
substance.
Gelatin, NF, is a product obtained by partial
hydrolysis of collagen obtained from the skin, white
connective tissue, and bones of animals.
It is found in commerce in the form of a fine powder,
Normally, hard gelatin capsules
contain between 13 and 16% of
moisture.
moisture may be absorbed or
released by gelatin capsules,
depending upon the environmental conditions,
in high humidity, capsules absorb moisture and
become distorted and lose their rigid shape.
but in extreme dryness, some of the moisture
normally present in the gelatin capsules may be
lost, and the capsules become brittle and
crumble.
Thus capsules should be stored in areas of low
humidity.
Gelatin is insoluble in cold water but soluble in
hot water, and in gastric fluid where a gelatin
capsule rapidly releases its contents.
Gelatin, being a protein, is digested and
absorbed.
Hard gelatin capsule shells are manufactured
mechanical dipping of manganese bronze pins of the
desired shape and diameter to the desired depth and
time into a reservoir of the melted gelatin mixture,
maintained at a constant temperature to achieve the
desired degree of fluidity.
Then the plate and the pins slowly lifted from the
gelatin bath and gently dried by a flow of
temperature and humidity controlled air
Capsule Sizes
Empty gelatin capsules are manufactured in

various sizes, varying in length, in diameter, and

capacity.

For human use, empty capsules ranging in size

from 000 the largest, to 5 the smallest are

commercially available.
 Preparation of Filled Hard Gelatin Capsules

The preparation of filled hard gelatin capsules may be

divided into the following steps:

1. Preparing the formulation

2. Selecting the capsule size.

3. Filling the capsule shells.

4. Cleaning and polishing the filled capsules.

. Preparing the formulation

Preformulation studies are used to determine if the

bulk powders may be blended together as such, or if
they require reduction of particle size or processing
into formed granules.

Dry Powder
Milling
To achieve uniform drug distribution through out a
powder mix, it is advantageous that the density and
particle size of the drug and non-drug components
are similar. This is achieved by particle size
reduction (milling).
Diluent

Generally, hard gelatin capsules are used to

encapsulate between about 65 mg and 1 g of

powdered material, including drug and any di­luent

required.

If the dose of the drug to be placed in a single

capsule is smaller than 65 mg to produce the proper

fill, lactose, microcrystalline cellulose, and

pregelatinized starch are common diluents used in

capsule filling. But when the amount of drug is large

enough to fill a capsule completely, a diluent may

not be required.
Lubricant

a lubricant as 1% Magnesium stearate is utilized to

prevent adhesion and facilitate the flow of the

powder in capsule filling machine.

Glidant

The powder mixture or granules must be free-

flowing to allow passage from the hopper by the

addition of a glidant such as 1% silicon dioxide.

Lubricant and Glidant are used to improve filling

properties.
Wetting agent

Addition wetting agents, as sodium lauryl

sulfate, in capsule facilitate the wetting

of the drug substance by gastrointestinal fluids

to enhance dissolution, and overcome the

problem associated with water-insoluble

lubricant as magnesium stearate which can delay

the dissolution of the drug and its absorption.

Eutectic mixtures

Eutectic mixtures or mixtures that tend to liquefy,

may require a diluent or absorbant such as
magnesium carbonate, kaolin, or light magnesium
oxide to separate physically the interacting agents
and to absorb any liquefied material.
Liquids
Gelatin capsules are
unsuitable for the
encapsulation of
aqueous liquids,
because water softens
the gelatin to produce
distortion of the
However,
capsules. some liquids such as fixed or volatile oils
that do not interfere with the stability of the gelatin
shells may be placed in gelatin capsules which then
may be sealed to ensure the retention of the liquid
(soft gelatin capsules)
Semisolids
This system can be used for both
liquid and solid active ingredients.
Mixtures for filling need only be
liquid when filled and should be
semisolid after being inside the capsules.
The materials to be filled must be either
thermosoftening or thixotropic in nature to be
liquefied by heating or shearing forces using heated
hopper with a stirrer and revert to the solid state
within the capsule shell.
Used for potent drugs to improve uniformity of
filling.
Granules and Pellets

Granules and Pellets are

packed in capsules instead
of powder to produce
modified release patterns.

Granules are produced

by granulation and are
more irregular than
pellets which are
spherical and produced
by microencapsulation
Capsules within capsules:
If one ingredient must be separated
from others in the formulation, a small
capsule, such as a No. 5, may be filled
with one powder and placed into a
larger capsule with the remaining
ingredients in the formulation.

Tablets within capsules:

Small tablets are filled into capsules to
produce special release forms or to
separate incompatible ingredients.

This small tablet can be placed inside the capsule

following the addition of a small quantity of the powder
and the filling completed.
Beads Granules Powders

Pastes Capsules Tablets

Liquids
I. SELECTION OF CAPSULE SIZE
The selection of capsule size is best done during the
development of the formulation, because the amount
of inert materials to be employed is dependent upon
the size or capacity of the capsule to be selected.

The density and compressibility of a powder or a

powder mixture will largely determine to what extent
it can be packed into a capsule shell.
The amount may vary according to the degree of
pressure used in filling the capsules.
Determination of capsule fill weight

To determine the size of capsule to be used or

the fill weight for a formulation the following
relationship is used:

Capsule fill weight =

Tapped Bulk Density of Formulation X Capsule
Volume
III. Filling the capsule shells

1."Punch" Method

2. Hand-Operated Capsule Filling Machines

3. Automatic-Operated Capsule Filling

Machines
"Punch" Method
Used for filling a small number of capsules in the

pharmacy, at the prescription counter.

The ingredients are triturated to the same particle

size and then mixed by geometric dilution.

The powder is placed on a powder paper or

ointment slab and smoothed with a spatula to a

height approximately half the length of the capsule

body.
The base of the capsule is held vertically and the

open end is repeatedly pushed or "punched" into

the powder until the capsule is filled;

The cap is then replaced to close the capsule. Each

filled capsule is weighed using an empty capsule as

a counterweight.

Powder is added or removed until the correct

weight has been placed in the capsule.

The filled capsule is tapped so that no air spaces

are visible within the contents.

[Link]
hand-operated capsule machines
Pharmacists that prepare capsules on a regular or

extensive basis may use hand-operated capsule

machines.

These machines are available in capacities of 24,

96, 100, and 144 capsules.

First, the plates are adjusted to hold the capsule

bodies in place while the caps are removed all at

one time.

The caps remain in place in the top of the machine

Then the plates are adjusted again so that the

capsule bodies will "drop" into place so that the

tops are flush with the working surface of the

plate.

The formulation powder is poured onto the plate

and special spreaders are used to fill the individual

capsules.

The combs are used to tamp (compress) and pack

the powder into the capsules.

All of the caps are then returned to the capsule

bodies, and the closed capsules are removed from

Automatic-Operated Capsule Filling Machine

Machines developed for industrial use can

automatically remove the caps from empty capsules,

fill the capsules, replace the caps, and clean the

outside of the capsules at a rate of up to 165,000

capsules and greater per hour.

SEALING of Gelatin capsules
In this process, the two capsule parts are sealed

with a gelatin or polymer band at the joint of the cap

and body.
developed in which
A tamper-resistant seal on hard gelatin capsules was
the contact areas of
the cap and body are
wetted with a
mixture of water and
ethanol to soften the
gelatin and then
thermally bonded at
104° to 113oF to form
the seal.
CONI-SNAP Hard gelatin capsule

A recent innovation in capsule

shell
design, where the two halves
of the
capsule shells are enable to be
positively joined through
locking
grooves in the shell walls.
The two grooves fit into each
other
and ensure reliable closing of
IV. Cleaning and polishing the filled capsules

Capsules prepared on a small scale or on a large scale

may have small amounts of the powder adhering to

the outside of the capsules.

This powder should be removed before packaging or

dispensing to improve the appearance of the capsules

and to preserve their quality of being tasteless on

administration. On a large scale, many capsule-filling

machines are affixed with a cleaning vacuum that

removes any extraneous material from the capsules.

Another proposed cleaning method is to put the

capsules in a container filled with sodium

bicarbonate, sugar, or sodium chloride, and gently

roll the container.

Then the container contents can be poured into a

ten-mesh sieve where the "cleaning salt" will pass

through the sieve.

 Soft Gelatin Capsules
Soft gelatin capsules (soft elastic gelatin capsules) or
(softgels) are prepared from continuous gelatin shells to
which glycerin or a polyhydric alcohols such as sorbitol has
been added to render gelatin elastic or plastic-like.
Soft gelatin capsules may be oblong, elliptical (oval), or
spherical round, oval, oblong, tube in shape., They may
also be prepared of single or two-tone color,
 1. Water immiscible, volatile and nonvolatile liquids
Application of Soft Gelatin Capsules
such as vegetable and aromatic oils, aromatic and

aliphatic hydrocarbons, chlorinated hydrocarbons,

ethers, esters, alcohols, and organic acids.

2. Water miscible, nonvolatile liquids such as

polyethylene glycols, and nonionic surface active

agents as tween 80.

3. Solids may be encapsulated into soft gelatin

capsules as

solutions in one of the suitable liquid solvents, as

suspensions, or as dry powders, granules, or

 Liquids which can easily migrate through the

capsule shell cannot be encapsulated into soft

gelatin capsules.

These materials include:

Water, above 5%, and low molecular weight

water soluble and volatile organic compounds

such as alcohols, ketones, acids, amines, and

esters.
Advantages of Soft Gelatin Capsules
1. They permit liquid medications to become easily

portable.

2. Comparing the degree of irritation or ulcerogenic

potential of soft gelatin capsule formulations

with a tablet formulation, Capsule formulations

had a reduced ulcerogenic potential when

compared to the tablet formulation.

3. Dose uniformity is optimized, because the drug is

dissolved or dispersed in a liquid which is then

dosed
4. Improve drug stability by resist gaseous diffusion

and contain no water, thus protect drugs sensitive

to oxidation or hydrolysis on long term storage.

5. Good bioavailability of drugs than from the

commercial tablets or capsules, that dissolved or

dispersed in a water miscible or oily liquids, thus

when the capsule ingested, the drug dispersed as

solution or emulsion to give a drug dispersion of

high surface area

Preparation of Soft Gelatin Capsules

In a soft gelatin capsule formulation the medicament

is in solution or is dispersed as a fine suspension in
either a hydrophilic vehicle or a hydrophobic base.

Formulation of soft gelatin capsules

There are two main aspects to be considered during
the formulation of soft gelatin capsules:
The composition of the gelatin shell and the
composition of the fill material.
 Formulation of the gelatin shell

The composition of the soft capsule shell consists of

two main ingredients: gelatin and a plasticize (e.g.

glycerol). Water is used to form the capsule and it

may be desirable or even necessary to add other

additives such as preservatives, dyes, opacifiers and,

rarely, flavours and drugs.

 Gelatin
To produce shells with a greater flexibility than hard
gelatin capsules it is necessary to control carefully the
viscosity and strength of the gelatin used in production.

If the viscosity of aqueous gelatin solution is too low, a

thin,
low strength shell is produced which has the
disadvantage of
requiring prolonged drying.
 If the viscosity of the gelatin solution is too high, a
thick
The mechanical properties of the gelatin shells are
film is produced which may be too hard and brittle.
controlled by choice of gelatin grade and by adjusting
also
the concentration of plasticizer in the shell.
require higher sealing temperatures during
 Plasticizers
The main plasticizer used for soft gelatin capsules is
glycerol.
Sorbitol and propylene glycol have also been used
but they are normally added in combination with
glycerol. Plasticizers are added in relatively large
concentrations. The greater the plasticizer content
the greater the flexibility of the shell. (0.3-1.0 parts
of dry plasticizer to 1 part of dry gelatin).
Low ratios 0.3-0.5 are used for oily liquid fills,
(0.4-0.6) for oily fills with added surfactant,
(0.6-1.0) for water-miscible fills and chewable
capsules.
 Water
The demineralized water content of gelatin solution
used to produce a soft gelatin capsule shell depends
on the viscosity of gelatin used (0.7-1.3 parts of
water to each part of dry gelatin), 1: 1 ratio being
typical.

Preservatives
Preservatives are added to prevent mould growth in
the gelatin shell. Potassium sorbitate and methyl,
ethyl and propyl hydroxybenzoate (methyl-, ethyl-
and propylparaben) are common additives.
 Colours
A wide range of colours can be incorporated into
soft gelatin shells
Water-soluble dyes (synthetic and vegetable),
insoluble inorganic and organic pigments and lakes.

Opacifiers
Titanium dioxide is the most common. It is added in
concentrations of about 0-0.5%.

Enteric treatment
Enteric properties can be imparted to soft gelatin
shells by coating with 4% cellulose acetate
Formulation of the capsule contents

Any non-aqueous liquid or powdered solid in

suspension can be filled into soft gelatin capsules.
It is possible to fill soft gelatin capsules with a very
wide range of materials.
Suspensions, pastes, drugs in solution in either oils,
self-emulsifying oils or water-miscible liquids.
Limitations for fill materials
Drugs or excipients containing large amounts of water
or other gelatin solvents cannot be incorporated.
It is not recommended to fill emulsions (whether they
be o/w or w/o) since they are unstable and will crack
as the water is lost from the shell in the
manufacturing process.
Surfactants may have a deleterious effect on the
capsule seal.
Extremes of pH must be avoided. pHs below about 2.5
attack the gelatin leading to hydrolysis and leakage
and pHs above about 7.5 have a tanning effect on the
gelatin, and affecting the solubility of the shell.
Liquid vehicles
Water-immiscible oils or water-miscible liquids.

Water-immiscible oils:
Either volatile or non-volatile oils,
Fixed aromatic vegetable oils,
Aliphatic, aromatic and chlorinated hydrocarbons,
Liquid ethers and esters.
Water-miscible liquids (hydrophilic)
Polyols as Polyethylene glycols with low molecular
weight (400-600) since they are liquid at ambient
temperatures. Alcohols as isopropyl alcohol,
polyglycerols, triacetin, glyceryl esters, sorbitan
esters, sugar esters and polyglyceryl esters.
Propylene glycol and glycerol can be used, but the
concentration must be low, (5-10%), in order to
prevent migration into the gelatin and softening of
the shell.
Suspensions
The particle size of the solid should be reduced to
less than 180 µm to pass through the filling head.
Insoluble drugs can be dispersed (with suspending
agents and surfactants) in the above vehicles or
combinations of vehicles.
Suspending agents are added to prevent settling
and maintain homogeneity

• For oily bases (beeswax, paraffin wax,

ethylcellulose
and hydrogenated vegetable oil)

• For non-oily bases (solid glycol esters as PEG

Surfactants as polysorbate 80 (Tween 80) are often
added as wetting agent.
Caking of suspensions in soft gelatin capsules can
be avoided by rheological control of the vehicle.
Preparation of Soft Gelatin Capsules
 Preparation
Soft ofmay
gelatin capsules Soft Gelatinby:
be prepared Capsules
The plate process, using a set of molds to form the

capsules.

The die processes (rotary or reciprocating

processes)

more efficient and productive processes

  A warm sheet of gelatin (plain or colored) is
the plate
placed on
process
the bottom plate of the mold.
 The liquid medication is poured on it.
 Then a second sheet of the prepared gelatin is
carefully
laid in place on top of the medication, and the top
plate
of the mold is put in place.
 The entire mold is then subjected to a press where
pressure is applied to form, fill, and seal the
capsules
simultaneously.

 e rotary die process
he
 Liquid gelatin flowing from an
overhead tank is formed into
two continuous ribbons by the
rotary die machine and
brought together between
twin rotating dies.
 At the same time, metered fill material is injected
between the ribbons at the moment that the dies
form pockets of the gelatin ribbons.
 These pockets of fill-containing gelatin are then
sealed by pressure and heat.
 The soft gelatin capsules may be prepared of
single or two-tone color, the latter resulting from
the employment of two different colored ribbons
of gelatin to form the sides of the capsule.
Manufacturing process
 •
rotary
The reciprocating die process is similar to the

e reciprocating die process

process in that ribbons of gelatin are formed and
used to
encapsulate the fill,

• But it differs in that the gelatin ribbons are fed

between a
set of vertical dies that continually open and close
to form
rows of pockets in the gelatin ribbons.

•
are
These pockets are filled with the medication and

sealed, shaped, and cut out of the film as they

progress
through the machinery.
As the capsules are cut from the ribbons, they fall
 containers

• Some containing packets of a desiccant to

prevent the

absorption of excessive moisture by the

capsules.

• Soft capsules have a greater tendency than do

hard

capsules to soften and adhere to one another,

and they

must be maintained in a cool, dry place.