Hard Gelatin Capsule

Capsule
The word capsule is derived from the Latin
“Capsula” meaning a small box. In pharmacy,
the word capsule is used to describe the
solid unit dosage form of medicament in
which the drug(s) is enclosed in a practically
tasteless, hard or soft soluble container or
shell made up of a suitable form of gelatin.
♣ Example: •Ampicillin capsule
•Amoxycillin capsule
•Ciprofloxacin capsule 2
In pharmacy, the word capsule is used
to describe an edible package made from
gelatin which is filled with medicines to
produce a unit dose, mainly for oral use.

Types of Capsule
Depending upon the form of capsule shell,
the capsule may be classified into two types
as:
1. Hard Gelatin Capsule (Double piece)
2. Soft Gelatin Capsule (Single Piece)
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 HARD GELATIN
CAPSULE
Hard gelatin capsule consists of a cylindrical body &
cap which fit one inside the other together after
filling.
Most of the capsules are hard gelatin capsule. The
form of drugs within the hard capsule may be either
powder or granule.
Capsules shells are made up of to cylindrical halves,
one slightly large in diameter but shorter in length
and the other slightly shorter in diameter and longer
in length. The drug is filled in the narrower and
longer half over which the other half is fitted as a
cap.
The hard gelatin capsule is made in a range
of eight sizes from size 000, the largest, to
size 5, the smallest. The most popular sizes
in practice are size 0 through to 4.

Fig: Hard gelatin capsules showing

Fig: The actual size & fill volumes of Hard
relative size.
gelatin capsule. The larger, narrower part of
the capsules is the body and the smaller,
wider part is the cap
Properties of Hard Gelatin capsule:
1. Usually cylindrical in shape.
2. Their boundary wall is firm and rigid, not
flexible.
3. Only solid medicaments are filled into
the shell.
4. The hard gelatin capsule shell usually
contain plasticizers, preservatives, water,
color, flavors and sugar.
5. Hard gelatin capsule contains less moisture
(13-16%).
6. It requires two steps of formulation process.
First, the shell formation and then the filling
process completed.
7. Volatile oil substance is not suitable for
filling.
8. Hard gelatin capsules usually contain 30-600
mg.
9. High bloom gelatin are used. Gelatin is 0.4:1
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This is because of the following reason---
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 Other advantages of Capsule
Hard gelatin capsules are tasteless, odorless and
can be easily administered.
Hard gelatin capsules usually provides uniform
release and ready bioavailability of the contained drug
in GIT.
They are easy to handle and carry.
They are flexible than tablets.

Presentation of a drug in capsules rather than in

tablets allows quicken submission of a new drug for
clinical trials, because fewer development problems are
involved.
Limitation
of Hard
Gelatin
Capsule

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1. More expensive than tablets.

• 2.Capsules are not usually used for the

administration of extremely soluble materials
such as KCl, KBr or NH4Cl. Since the sudden
release of such compounds.
3. Capsules should not for highly effervescent.
Effervescent materials may cause the capsule
to soften.
4. Product cost is expensive more than tablets.
5.Some absorb moisture and degraded.

6.Some hydroscopic capsule are made by

12-13% water. Hydroscopic ingredient
absorb water from capsule shell. Than it
become brittle.

7.Gelatin is the major component of the

capsule. It is stable in the air when dry, but
is subject to microbial attack when it
becomes moist.
 GELATIN
Gelatin is a heterogeneous product obtained by the
partial irreversible hydrolysis of collagen derived
from the skin, white connective tissue, hide portion,
frozen pork and bones of animals.
Commercially, gelatin is prepared from the suitable
by-products of slaughtered cattle, sheep & hogs.
Gelatin is the major component of the capsule and
has been the material from which they have
traditionally been made.
Gelatin is protein in nature, digested by proteolytic
enzyme and absorbed.
Characteristics of Gelatin:
1. Gelatin occurs in sheets, flakes, shreds or
as a coarse or fine powder.
2. It is faintly yellow or amber & process slight
characteristic odor and taste.
3. When dry it is stable in air but when moist,
it is subject to bacterial decomposition.
4. It is insoluble in cold water, most
immiscible solution, volatile and fixed oils.
5. Gelatin is soluble in hot water.
There are two main types of gelatin:
1.Type-A: Which is produced by acid hydrolysis.
This type of gelatin exhibits an isoelectric point
between pH 7 and pH 9. It is incompatible with
anionic compounds such as acacia, tragacanth
and agar.
2.Type-B: This is produced by basic hydrolysis.
It has isoelectric point in the region of pH 4.7
and 5.
The choice of manufacturing method depends
upon the nature of the raw materials.
Skins are mainly acid processed whereas bones
are usually basic processed.
Gelatin is the major component of capsules due to
their five properties as below:
1. It is non-toxic, widely used in food-stuffs, and
acceptable for use worldwide.
2. It is readily soluble in biological fluids at body
temperature.
3. It is good film-forming material, producing a strong
flexible film. The wall thickness of a hard gelatin
capsule is about 100μm.
4. Solutions of high concentration, 40% w/v, are mobile at
50°C. Other biological polymers, such as agar, are not.
5. As a solution in water or a water-glycerol blend it
undergoes a reversible phase change from a sol to a
gel. This property enables films of gelatin to be
prepared easily.
Manufacture of Gelatin
The preparation of gelatin is not a
hard task. Bones and skins of animal
are used for the preparation. It is a
stepwise process and takes a long
time.
Here a schematic representation is
given to prepare gelatin:
 Dry Bone Calf skin Pork skin

5% HCl Lime10%
Wash
10-15 days 6-12 weeks

Wash Acid
Lime 1o% 1-5% HCl
4-8 weeks 10-30 hours
Water wash
Lime removal 10-30 hours

pH adjustment
Acid removal
Hot water extraction

Filter
Vacuum concentration

Cool to solidify
Air dry

Mill to size
 Process
Hard gelatin capsules are manufactured by fully
automatic machines housed in complex air
conditioned buildings. As a result a small number
of specialist companies supplying empty capsule
shells to the pharmaceutical industries.
The two major producers in the world are the
American companies:
1. Eli Lilly
2. Parke Davis

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 The first part of the manufacturing process
is the preparation of raw materials.
1. A concentrated gelatin solution is prepared in
hot demineralized water in a jacketed pressure
vessel.
2. A vacuum is applied to the solution to remove
any entrapped air.
3. Aliquots of the solution are dispensed into
suitable container.

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4. Required quantities of dye solution and
preservatives are added to them.
5. The viscosity of each mix is measured and
adjusted to a target value.
6. The parameter is used to control the
thickness of capsule shell walls in
production.
7. The mixers are then transferred to heated
storage hoppers on the manufacturing
machines.
The manufacturing machines are 10m long
and 2m wide, consists of half which are
mirror images. On one half the caps are
made and on the other bodies.
The moulds, called ‘pins’, are made of
stainless steel and are mounted in sets of
metal strips, called ‘bars’.
There are approximately 44,000 moulds
pins per machine. It is housed in large room
having controlled humidity & temperature.
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 At the front end of the machine is a
hopper, called a ‘dip pan’ or ‘pot’. This
holds a fixed quantity of the prepared
gelatin solution at a constant temperature,
between 45°C and 55°C.
1. The level of solution is maintained by
an automatic feed from the storage hopper.
2. Capsule shells are formed by dipping
sets of ‘moulds’ at room temperature, into
this solution.
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3. A film is formed on the surface of each
mould by gelling.
4. The moulds are slowly withdrawn and then
rotate during their transfer to the upper level
of the machine in order to form a film of
uniform thickness.
5. Groups of pin bars are then passed through
a series of drying chambers in which large
volumes of controlled humidity air are
blown over them.
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6. At the rear of the machine the bars are
transferred to the lower level and travel
through further drying chambers back to
the front of the machine.
7. In the automatic section, the dried films are
removed from the moulds.
8. Cut to the correct lengths, the two halves
joined together and complete capsule shells
derived from the machine.
9. The moulds pins are cleaned and lubricated
for the start of the next cycle.
Stripping

Cutting

Joining

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10. The finished capsule shells now pass through a
series of checking process which can either be
manual, mechanical or electronic.
11. If required, the capsules are printed at this stage.
Printing in several varieties as follows:
Linear Printing Circular Printing
a. Double color oriented a. Double color oriented
b. Single color oriented b. Single color oriented
c. Regular Linear printing c. Regular circular printing

12. The information printed is usually either the

product name or drug strength, the company name
or some other identifying mark.
Thus the preparation of capsule shells can be represented as:-

Melted Gelatin Pins are dipped and Pass Cool

spun into Gelatin Air

Drying

Join of Body Trimmed to Removal from pins

and Caps proper length
Formulation of Capsules
♣ Preparation of Filled Hard Gelatin Capsule:
The preparation of hard gelatin capsules may
be divided into the following steps:
Developing and preparing the formulation
and selecting the size capsule
Filling the capsule shells
Capsule sealing (optional)
Cleaning and polishing the filled capsules
Capsule formulation and selection of capsule
size:
Hard gelatin capsules are generally used to
encapsulate between about 65mg and 1gm of
powder material, including drug and any diluent
required. All formulations for filling into capsules
must possess two basic requirements that are:
Be able to be accurately dosed into the
capsule shell.
Release their active contents in a form
that is available to the patients.
If the dose of the drug or the amount of drug
to be placed in a single capsule is inadequate
to fill the volume of the capsule, a diluent is
necessary to add the proper degree of bulk to
the drug to produce the proper fill. Lactose in
a common diluent used in capsule filling.
Lubricants are used to facilitate the flow of
the powder when an automatic capsule-filling
machine is utilized. Magnesium stearate,
Calcium stearate or talc (about 0.25–1%)
generally used as lubricant in capsule
making.
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 density of formulation ×
capsule volume

5 to 10% excess of each ingredient is

calculated just to compensate for the loss of
material during operation.
♣ Filling the capsule shells:
Capsule filling may be operated hand or machine. In
both processes the single mechanism is involved which
are as follows: ------
First the weighed amount of active ingredients and
additives are prepared for the filling operation. Now the
capsule shells are taken to separate them into cap and
body. The body is then filled with the prepared powder
mixture or granules. Now the cap is pressed on the body
to close it.
A properly filled capsule should have its body filled
with the drug mixture and its cap fully extended down the
body so as to enclose the powder in the body. The cap is
not used to hold powder but to retain it. Finally the filled
capsule shells are ejecting for cleaning and polishing.
 CAPSULE FILLING MACHINE
• The machines for the industrial scale filling
of hard gelatin capsules come in great
variety of shapes & sizes & mechanisms.
• Some common machineries for the capsule
filling are-
• 1. Augur
• 2. Dosator
• 3. Tamping finger & dosing disc
♣ Capsule sealing:
The following process may seal the filled capsules: -
A heat welding process that fuses the capsule cap to
the body through the double wall thickness at their
juncture.
Utilizing a melting point lowering liquid wetting agent
in the contact areas of the capsule’s cap and body
and then thermally bonds the two parts using low
temperatures (40-450C).
Extemporaneously prepared capsules may be
sealed by lightly coating the inner surface of the cap
with a warm gelatin solution immediately prior to
placement on the filled capsule body.
♣ Cleaning and Polishing:
Capsules prepared on a mall scale or on a large
scale may have small amounts of the powder
formulation adhering to the outside of the
capsules. This powder which may be bitter or
unpalatable, should be removed before
packaging or dispensing to improve their quality.
Empty or filled capsules are untouched by hands,
sanitary handling is very much necessary. In
dispensing, wipe the filled capsule with clean
surgical gauze or cleaning tissue.
 The following methods are used for the final finishing of
capsule:-
1. Pan polishing: The tablet coating pan may be used to
remove dust and polishing capsules. A polyurethane or
cheese cloth liner is placed in the pan and the liner is
used to trap the removed dust as well as to impart a
gloss to the capsules.
2. Cloth dusting: On this method, the bulk-filled
capsules are rubbed with a cloth that may or may not
be impregnated with inert oil. It imparts a somewhat
improved gloss to the capsules.
3. Brushing: In this procedure, capsules are fed under
rotating soft brushes, which serve to remove the dust
from the capsule shell. This operation must be
accompanied by a vacuuming for dust removal.
 Quality Control of Capsule
Whether capsules are produced on a small or
large scale, all of them are required to pass the
quality control tests. The hard or soft gelatin
capsules should be subjected to following for their
standardization:
• Shape and Size • Color
• Thickness of the capsule shell • Disintegration Test
• Weight variation test
• Percentage of medicament test
• Leaking test for semisolid and liquid ingredients from
soft capsules.
♣ Disintegration test:
For performing disintegration test on
capsules one capsule in each tube which are
then suspended in the beakers to move up
and down for 30 minutes into a
thermostatically controlled fluid at 37°C.
To fully satisfy the test, the capsules
disintegrate completely into a soft mass
having no palpably firm core and only some
fragments of the gelatin shell.
♣ Dissolution test:
A suitable volume of dissolution medium like distilled
water, HCl or phosphate buffer at a pH of 7.3 is filled
in the glass vessel which submerged in the water
bath maintained at 37°C. The capsule to be tested
in introduced in the basket and fitted in position.
The motor is started and its revolutions adjusted.
The samples are withdrawn at specified intervals
and filtered immediately through a suitable filter
medium.
Generally 5ml sample solution is withdrawn each
time which is replaced with 5ml of medium to
maintain a constant volume in the vessel.
The sample are tested by chemical analysis
for proportion of drug dissolved which
should meet the requirements as stated in
the monograph.
Since the capsule shells interfere with the
analysis, the contents of a specified number
of capsules can be removed and the empty
capsule shells dissolved in the dissolution
medium before proceeding with the sample
in and chemical analysis.
♣ Weight variation test:
Ten capsules are individually weighted and
the contents removed. The emptied shells are
individually weighed and the net weight of the
contents calculated by subtraction.
From the results of an assay, the weight of the
contents for each individual capsule is
determined and compared with the average
weight of contents.
The capsules pass the test if the weight of
individual capsules falls within 90-110% of the
average weight.
Moisture Permeation Test:
The USP requires determination of the moisture
permeation characteristics of single unit and
unit dose containers to assure their suitability
for packaging capsules.
The degree and rate of moisture penetration is
determined by packaging the dosage unit with a
color revealing desiccant pellet.
The packaging unit then exposed to known
relative humidity over a specified time and
observed the desiccant pellet for color change
and compared the pre-and post-weight of the
packaged unit.
 Packaging of capsules
• Hard gelatin capsules may be retail
packaged using any modern packaging
equipment, including the electronic type.
• Capsules may be packaged in glass or
plastic container or may be strip-packaged.
Such packaging involves tight closures and
plastics having a low moisture vapor
transfer rate.
• Since, strip packaging is usually done by
specialist in the field, their advice should be
solicited, and adequate tests for strips
should be made.