UNIT 3 CAPSULES

Capsules are a solid dosage form in which the drug substance is enclosed in a
water soluble shell or an envelope. A capsule shell is made from gelatin. The
capsules are available both as hard capsule and soft capsule
Advantages of capsules:
1. The drugs having unpleasant odour and taste can be administered by
enclosing them in a tasteless shell.
2. They are smooth, become very slippery when moist and can be easily
swallowed.
3. They are economical.
4. They are easy to handle and carry.
5. The capsules release the medicament as and when desired in gastro-
intestinal tract.
6. Capsules are made from gelatin and hence they are therapeutically inert.
7. They are attractive in appearance.

Disadvantages of capsules:
1. The hygroscopic drugs cannot be filled in capsules. They absorb water
present in the capsule shell and hence make it very brittle, which ultimately
breaks into pieces.
2. The concentrated preparations which need previous dilution are unsuitable
for capsules because it may lead to irritation in stomach if administered as
such.
Types of Capsules:
Capsules are available in two types:
1. Hard gelatin capsules
2. Soft gelatin capsules

1. Hard Gelatin Capsules

 These are used for administration of solid medicaments.
 The capsule shell is prepared from gelatin, color and titanium dioxide to
make it opaque.
 It consists of two parts i.e. body and cap.
 The powdered material is filled into the cylindrical body of the capsule and
then the cap is placed over it.
 The empty capsules are available in various sizes.
 They are numbered according to the capacity of the capsules.
 The number starts from 000 and goes up to 5.

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2. Soft Gelatin Capsules
 These are used for administration of liquid medicaments.
 Soft gelatin capsules are available in round, oval and tube like shapes.
 They are made from gelatin.
 The gelatin is plasticized by the addition of glycerin and sorbitol etc.
 The soft gelatin shell may contain a preservative to prevent the growth of
fungi.
 They are used to enclose liquid medicaments-oils, suspensions, food
concentrates and ophthalmic products.

HARD GELATIN CAPSULES

HARD GELATIN CAPSULES:

 Hard gelatin capsules also known as hard-shell gelatin capsules or two-
piece capsules are solid dosage forms in which one or more medicinal
agents and/or inert materials are enclosed within a small shell.
 A hard gelatin capsule shell consists of two prefabricated, cylindrical
sections (a cap and a body) each of which has one rounded, closed-end
and one open end.
 The body has a slightly lower diameter than the cap and fits inside the
cap.

COMPOSITION AND SIZE:

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MATERIALS FOR HARD GELATIN CAPSULES PREPARATION:
1. Fillers (or diluents):
 Active ingredient is mixed with a sufficient volume of a diluent, usually
microcrystalline cellulose, lactose, mannitol, starch, or dicalcium
phosphate, to increase the bulk of the formulation.

2. Glidants:
 Glidants are finely divided dry powders added to the formulation in
small quantities to improve their flow rate from the hopper and into the
body of the capsule during the filling process.
 Glidants, such as colloidal silicon dioxide, powdered silica gel, starch,
talc, and magnesium stearate, improve flow by
a. Reducing the roughness by filling surface irregularities.
b. Reducing attractive forces.
c. Reducing electrostatic repulsion.
 The optimal concentration of the glidant used to improve the flow of a
powder mixture is generally less than 1% w/w.

3. Lubricants:
 Capsule formulations usually require a lubricant just as the tablet
formulations to reduce powder adhesion to the machine parts,
especially during plug formation.
 Lubricants ease the ejection of plugs by reducing the adhesion of
powder to metal surfaces and friction between the sliding surfaces in
contact with the powder.
 The most common lubricants for capsule formulations are hydrophobic
stearates, such as magnesium stearate, calcium stearate, and stearic
acid.

4. Surfactants and wetting agents:

 Surfactants may be included in capsule formulations of poorly water-
soluble drugs to reduce the contact angle, increase the wettability of
drug particles, and enhance drug dissolution.
 The most commonly used surfactants in capsule formulations are
sodium lauryl sulfate and sodium docusate (sodium dioctyl
sulfosuccinate).
 In addition, a hydrophilic polymer, such as HPMC, is sometimes used
as a wetting agent in the formulations of poorly soluble drugs.

5. Disintegrants:
 A disintegrant is frequently included to aid rapid disintegration and
dissolution of the contents.
 Common disintegrants used in hard gelatin capsule formulations
include croscarmellose sodium,crospovidone, and sodium starch
glycolate

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6.Gelatin:
 Main ingredient for making capsule shells.

7.Preservatives:
 To reduce the growth of microorganisms.
 sulfur dioxide which is added as the sodium salts, bisulfite or metabisulfite,
sorbic acid or the methyl propyl esters of para hydroxy-benzoic acid and the
organic acids, benzoic and propanoic acids

8.Opaquants/ Opacifying agent:

 To make the shells opaque.
e.g. titanium dioxide

9.colorant:
 To make capsules look distinctive and attractive.

PREPARATION OF EMPTY HARD GELATIN CAPSULE SHELLS:

1.Capsule formulation and selection of capsule size:

Limitations in properties of materials for filling the capsules:
 Must not react with Gelatin.
 Must not contain a high level of free moisture.
 The volume of unit dose must not exceed the sizes of the capsule available.
 To determine the size of capsule to be used or the fill weight for a
formulation the following relationship is used:
For powder:
Capsule fill weight = tapped bulk density of formulation  capsule body volume.
For liquids:
Capsule fill weight= specific gravity of the liquid  Capsule body volume  0.8

EMPTY CAPSULE SHELL PREPARATION:

Hard gelatin capsules are manufactured using a dip-coating method and the
various stages involved are as follows:

Step 1: Preparation of the gelatin solution (dipping solution)

Gelatin:
Gelatin possess some basic properties that make it suitable for the
manufacture of capsules:
1. It is non-toxic, widely used in foodstuffs 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
4. The gelatin films are homogeneous in structure, which gives them strength.
5. Solutions of high concentration, 40% w/v, are mobile at 50°C. Other
biological polymers, such as agar, are not.

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Production of gelatin
 Gelatin is produced by the hydrolysis of collagen. Animal skins and bones
(bovine or porcine) are the raw materials used for gelatin manufacture.
 There are two main types of gelatin: type A , which is produced by acid
hydrolysis and type B, which is produced by basic hydrolysis.
 The acid process takes about 7-10 days and is used mainly for porcine skins
while the basic process takes about 10 times as long and is used for bovine
bones.
 The bones must first be decalcified by washing in acid to give a soft sponge
like material called ossein, and calcium phosphates are produced as a
byproduct.
 The ossein is then soaked in lime pits for several weeks.
 After hydrolysis, the gelatin is extracted from the treated material using hot
water.
 The resulting weak solution of gelatin is concentrated in a series of
evaporators and chilled to form gels. This gel is then extruded to form
strand, which are then dried in fluidized bed system.
 The dried material is graded and then blended to meet the various
specification required.

Step 2: Dip-coating the gelatin solution on to metal pins (moulds)

 Capsule shells are manufactured under strict climatic conditions by dipping
pairs (body and cap) of standardized steel pins arranged in rows on metal
bars into an aqueous gelatin solution (25 – 30% w/w) maintained at about
50 ° C in a jacketed heating pan.
 Because the moulds are below the gelling temperature, the gelatin begins to
form a thin gelatin layer or film on the moulds.
 The rows of pins are arranged so that caps are formed on one side of the
machine while bodies are simultaneously formed on the opposite side of the
machine.

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Step 3: Rotation of the dip-coated pins
 Following adsorption of the gelatin solution on to the surface of the pins, the
bar containing the pins is removed and rotated several times to evenly
distribute the solution around the pins, correct gelatin distribution being
critical to uniform and precise capsule wall thickness and dome strength.

Step 4: Drying of the gelatin-coated pins

 Once the gelatin is evenly distributed on the mould, a blast of cool air is
used to set the gelatin on the mould.
 At this point, the gelatin is dried, and the pins are then passed through
several drying stages to achieve the target moisture content.

Step 5: Stripping and trimming

 After the gelatin is dried, the capsule is stripped off the mould and trimmed
to the proper length.

Step 6: Joining of the trimmed capsule shell

 Once trimmed, the two halves (the cap and body) are joined to the pre-closed
position using a pre lock mechanism.
 At this point, printing is done if needed before packing in cartons for
shipping.

Step 7: Printing
 After formation, the capsule shells can be printed to improve identification.
 Printing can be achieved using one or two colours, containing information
such as product name or code number, manufacturer’s name or logo and
dosage details.

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FILLING OF CAPSULE SHELLS:
Types of material for filling into hard gelatin capsule:
 Dry Solid:
 Powder
 Pellets
 Granules
 Tablets
 Semisolid:
 Thermosoftening mixtures
 Thixotropic mixtures
 Pastes
 Liquids: non-aqueous liquid
1)CAPSULE FILLING
 Capsule filling may be done by hand or machine. In both process the
single mechanism is involved which is as follows:
 the weighed amount of active ingredients and additives are prepared for
the filling operation.
 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.
 Finally the filled capsule shells are ejected for cleaning and polishing.

2)CAPSULE SEALING:
 The filled capsules may be sealed by the following process:
 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.

3)CLEANING and POLISHING CAPSULES:

 Small amounts of powder may adhere to the outside of capsules after filling.
The powder may be bitter or otherwise unpalatable and should be removed
before packaging or dispensing.
 On a small scale, capsules may be cleaned individually or in small numbers
by rubbing them with a clean gauze or cloth.
 On the large scale, many capsule filling machines are affixed with a
cleaning vacuum that removes any extraneous material from the capsules
as they exits the equipment.

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Basic steps in powder filling of Hard Gelatin Capsule
1. Loading of empty capsule shells in filling machine:
The empty capsule shells are placed into the shell hopper of the capsule filling
machine.
2. Rectification of the capsule shell:
The empty capsule shells are oriented in such a way so that they are all pointing
in the same direction, body-end downword.
3. Separation of the body and cap:
The caps are separated from the body and set apart in order to expose the bodies
for filling with powder materials.
4. Filling the body with formulation materials:
Filling of the capsule bodies is termed as dosing.
5. Joining of the body and cap:
After filling, the caps and bodies are rejoined to form the complete capsule.
6. Ejection of the filled capsule:
The capsules are ejected out of the machine and collected in appropriate
container.
 Almost the same set of operations are carried out whether capsules are
being filled with Bench-top manual apparatus for small scale
extemporaneous dispensing.
 High speed semiautomatic or automatic machines for large scale
industrial production.

CAPSULE FILLING MACHINES:

A. MANUAL CAPSULE FILLING MACHINE
Basic parts:
 Loading tray
 Cam handle
 Lever/long handle
 Pin/ Tamping plate
 Powder frame
 Sealing plate

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 STEPS:
1. The empty capsule shells are placed into the holes of the loading tray in
proper orientation ,i.e. body-end downward. This can be done manually or
with the help of an orienting machine.
2. The loading tray is placed on the bed of the filling machine and attached
properly.
3. The cam handle is pushed to lock the capsule bodies in the filling machine
with the help of sliding sheets.
4. The lever is pushed to separate the caps and the bodies of the capsules.
5. The loading trays with the caps is pulled up and kept aside.
6. The cam handle is pushed away to drop the capsule bodies in such a way so
that they are aligned with the machine bed.
7. The powder frame/tray is placed on the filling machine.
8. The premeasured amount of powder is poured within the powder frame and
spread uniformly to fill the bodies. The extra powder is moved on one side
and kept in the powder reservoir.
9. The tamping plate is lowered and locked by the clamp.
10.The tamping plate handle is turned round to compress the powder inside
the bodies which allows filling of more powders in each capsule.
11. The tamping plate is unlocked and raised. The remaining powder kept
aside in the powder tray reservoir is spread again to further fill up the capsule
bodies.
12.The loading tray with the caps is returned and positioned appropriately on
the filling machine.
13.The locking (sealing) plate having rubber top is lowered and clamped.
14.The lever handle is lowered down which pushes the bodies up into the caps.
This makes the bodies and caps rejoin to close the filled capsules.
15. The locking plate is lifted up after releasing the clamp.
16.The loading tray containing the filled and locked capsules is removed.
17.The prepared capsules are collected for subsequent de-dusting and
packaging.

Capacity: 30-300 capsules can be prepared in a single operation.

De-dusting of capsules:
The capsules are fed under rotating soft brushes, which serve to remove the
dust adhering on the top surface of the capsule shells.
This operation is accompanied by a vacuum for dust removal.
Packing:
Bulk capsules are packed by either blister or strip packing machine

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 B. SEMI-AUTOMATIC CAPSULE FILLING MACHINE:

STEPS:
1. Placement of the loading rings on the first turntable below the capsule shell
hopper and rectifier unit.
2. Rectification of the empty shells with the aid of the vacuum system.
3. Manual separation of the loading rings. This removes the caps from the
bodies. The upper ring is kept aside.
4. Placement of the lower ring containing the bodies on the second turntable
under the powder hopper.
5. Filling of the capsule bodies by discharging the powder from hopper. The
turntable is rotated to sequentially fill all the bodies placed in the lower ring.
6. The two parts of the ring are set together. The bodies and caps are now
ready to be closed.
7. The holing rings are placed on the pin plate and closed on the front side
with the closing plate.
8. By pneumatic pressure, the pins are used to push the bodies inside the caps
to lock the capsules.
9. The closing plate on the front side is released and the pins used again to
push the filled and joined capsules out of the holes.
10. The ejected capsules are delivers through the collecting tube into a
container.
PACKAGING:
Bulk capsules are packed by either blister or strip packing machine

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C.AUTOMATIC CAPSULE FILLING MACHINES:
 Most automatic capsule filling machines used in industry are of independent
type.
 In these capsule fillers, the measured amount of powder is first compressed
to form a plug.
 Then the plug is ejected inside the body of the capsule shell.
 PLUG (Slug): very soft compact mass made at low compression pressure (10-
200 N)
 Two types of mechanism involved in filling:
1. Dosing tube (Dosator)
2. Dosing disc and tamping finger
1.Dosator or Dosing tube
 The dosing tube or dosator is the most widely used type.
 The plug is formed inside a tube with a movable piston that applies a force
to form the plug.
 The piston also controls the dosing volume. The fill weight can be varied
over a wide range by a simple adjustment of the piston position.

2)Dosing Disk and Tamping Fingers(Pins)

 The fingers penetrate into the plate and consolidate the powder in the
cavities into plugs.
 Thus the plug is formed in a series of tamps and not in a single action as on
the dosator machines.
 The final plug is ejected into an empty capsule body by ejection pin.
 The dosing disc machines are of intermittent type.

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 SOFT GELATIN CAPSULES
 Soft gelatin capsules consist of a hermetically sealed outer shell of gelatin
that encloses a liquid or semisolid medicament in the unit dosage.
 Soft gelatin capsules are a completely sealed dosage form and cannot be
opened without destroying the capsules.
 Drugs that are commercially prepared in soft capsules include cyclosporine,
declomycin, chlorotrianisene, digoxin, vitamin A, vitamin E, and chloral
hydrate.

ADVANTAGES OF SOFT GELATIN CAPSULES

 As compared to other mode of administration soft gelatin capsules are

administered through oral route, very easy to swallow.
 Soft gelatin capsules are free from taste and odour.
 Soft gelatin capsules are in sealed form so they protect the inner fill from
oxidation and degradation.
 Opaque soft gelatin capsules also protect the inner fill from UV radiation
and photo sensitive products.
 It enhance patient compliance due to its elegant appearance.
 Suitable for medicaments like semisoli, oils, liquid forms.
 Soft gelatin capsules increase the bioavailability of API.

DISADVANTAGE OF SOFT GELATIN CAPSULES

 Soft gelatin capsules having difficulties in dealing with water soluble

materials.
 Soft gelatin capsules are highly sensitive to moisture.
 Soft gelatin capsules having difficulties in dealing with efflorescent
materials.
 Soft gelatin capsules having difficulties in dealing with deliquescent
materials.
 As gelatin is obtained from animal soure so soft gelatin capsules are not
suitable for people belongs to vegetarian group.
 Manufacturing procedure of soft gelatin capsules is complex as compared to
other dosage forms

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RATIONALE FOR SOFT GELS AS A DOSAGE FORM:
1) Improved drug absorption:
 Improved rate and extent of absorption and/or reduced variability, mainly
for poorly water-soluble drugs.
 Softgel can provide increased bioavailability and decreased plasma
variability.
2)Patient compliance and consumer preference:
 Easy to swallow.
 Absence of poor taste or other sensory problem.
 Convenient administration of a liquid-drug dosage form
3) Safety - potent and cytotoxic drugs:
 Avoids dust handling problems during dosage form manufacture:
 better operator safety and environmental controls
4)Oils and low melting-point drugs:
 Overcomes problems with manufacture as compressed tablet or hard-shell
capsules.
5) Dose uniformity for low-dose drugs:
 Liquid flow during dosage form manufacture is more precise than powder
flow.
 Drug solutions provide improved homogeneity over powder or granule
mixtures.
6)Product stability:
 Drugs are protected against oxidative degradation by lipid vehicles and
softgel capsule shells.
_________________________________________________________________________________

FORMULATION OF SOFT GELATIN CAPSULES:

 The composition of the soft capsule shell consists of three main ingredients:
(1) gelatin, (2) plasticizer, and (3) water. In contrast to hard gelatin capsules,
a relatively large amount (~30 % w/w) of plasticizers is added in soft gelatin
capsule shell formulation to ensure adequate flexibility.
 Water is used to form the capsule, and other additives are often added as
needed.

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1. Gelatin:
 Similar to hard gelatin shells, the basic component of soft gelatin shell is
gelatin.
 The properties of gelatin shells are controlled by the choice of gelatin grade
and by adjusting the concentration of plasticizer in the shell.
 The physicochemical properties of gelatin are controlled to allow
• Adequate flow at desired temperatures to form ribbons of defined
thickness, texture, mechanical strength, and elasticity.
• Ribbons to be easily removed from the drums, stretch during filling,
seal the temperature below the melting point of the film, and
dry quickly under ambient conditions to an adequate and a reproducible
strength.

Properties of Gelatin:
Bloom or gel strength: A measure of the cohesive strength of cross-linking that
occurs between gelatin molecules& is proportional to the mw of the gelatin Higher
the bloom strength, more physically stable the capsule shell. Bloom range:150-
250 g.
Viscosity of gelatin : It is a measure of the chain length & manufacturing
characteristics of gelatin film. The required viscosity of gelatin lies in between 25-
45mp.
Iron content: It is present in raw gelatin as well as water used in mfg. excess qty.
of iron can effect FD &C & react with organic compounds. Hence, iron is used in
the conc of not more than 15ppm.

2. Plasticizer:
 A plasticizer interacts with gelatin chains to reduce the glass transition
temperature (Tg) of the gelatin shell and/or promotes the retention of
moisture (hygroscopicity).
 The most common plasticizer used for soft gelatin capsules is glycerol.
Sorbitol, maltitol, and polypropylene glycol can also be used in
combination with glycerol.
 Glycerol derives its plasticizing ability primarily from its direct
interactions with gelatin.
 In contrast, sorbitol is an indirect plasticizer because it primarily acts as
a moisture retentive agent.
 Compared to hard gelatin capsules and tablet film coatings, a relatively
large amount (~30% w/w) of plasticizers are added in a soft gelatin
capsule formulation to ensure adequate flexibility.

3. Water:
 The desirable water content of the gelatin solution used to produce a soft
gelatin capsule shell depends on the viscosity of the specific grade of
gelatin used.
 It usually ranges between 0.7 and 1.3 parts of water to each part of dry
gelatin.

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  After the capsule is formed, most of the water is removed by drying. The
finished soft gelatin capsules contain 13–16 % w/w water.

4. Preservative:
 Preservatives are often added to prevent the growth of bacteria and mold
in the gelatin solution during storage.
 Potassium sorbate, and methyl, ethyl, and propyl hydroxybenzoate are
commonly used as preservatives.

5. Colorant and/or opacifier:

 A colorant and/or opacifier (e.g., titanium dioxide) may be added to the
shell for visual appeal and/or reducing the penetration of light for the
encapsulation of a photosensitive drug.
 The color of the capsule shell is generally chosen to be darker than that
of its contents.

6. Other excipients:
 Other, infrequently, used excipients can include flavors and sweeteners
to improve palatability and acid-resistant polymers to impart enteric
release characteristics.
 They can also be used to formulate chewable soft gelatin capsules,
 A chelating agent, such as ethylene diamine tetracetic acid (EDTA), can
be added to prevent chemical degradation of oxidation sensitive drugs
catalyzed by free metals in gelatin, such as iron.

MANUFACTURE OF SOFT GELATIN CAPSULES:

Is manufactured by four methods
1)Plate process
2)Rotary die process
3)Reciprocating die
4)Accogel machine

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

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2)ROTARY DISC METHODS:
1) In this machine the soft gelatin capsules are prepared & then filled
immediately with liquid medicaments it is having two hoppers & two rotating dies
2) Liquid mixture is placed in one hopper & the liquid medicament in other
Hooper.
3) The two rotating dies rotate in opposite directions when the fluid gelatin
mixture enters the machine from the hopper it produces two continuous ribbons .
4) These half shell of the capsule is formed.
5) At this stage the measured quantity of the medicament is filled in to it with
the stroke of a pump with the subsequent movement of the dies the other half
capsule is formed.
6) The two halves' of the capsules are sealed together by the heat & pressure of
the rotating dies.
7) As the die rolls rotate, the convergence of the matching die pockets seals and
cuts out the filled capsules

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3)ACCOGEL MACHINE:
 Accogel Capsule Machine Or Stern machine, uses a system of rotary dies but
is unique in that it is the only machine that can successfully fill dry powder
into a soft gelatin capsule
It consists of mainly 3 parts:
 Measuring roll
 Die roll
 Sealing roll
 As the measuring roll and die rolls rotate, the measured doses are transferred
to the gelatin-linked pockets of the die roll.
 The continued rotation of the filled die converges with the rotating sealing roll
where a second gelatin sheet is applied to form the other half of the capsule.
 Pressure developed between the die roll and sealing roll seals and cuts out
the capsules.
_________________________________________________________________________________

EVALUATION OF CAPSULE PRODUCTS:

Drug product testing is generally divided into three stages:

1. In-process testing, during the manufacture of the drug product. These

batteries of tests are carried out at predefined intervals during the product
manufacturing, by the manufacturing personnel, and their results recorded on the
batch record. Adverse findings in these tests
can be used as a guide to alter the manufacturing-process parameters.

2. Finished product testing, after the whole batch has been manufactured.
These tests help identify whether the batch is acceptable for marketing or its
intended usage.

3. Shelf-life testing, after the whole batch has been packaged. These tests
are frequently carried out after defined periods of storage at predetermined
conditions. They help to assign and verify the shelf life and usability of the drug
product.

1)INPROCESS TESTS:
Visual inspection of soft gelatin capsules is done to ensure absence of clearly
malformed, damaged, or improperly filled capsules. During the encapsulation
of soft gelatin capsules, the following parameters are usually closely monitored
and controlled:
 Gel ribbon thickness and uniformity across the ribbon
 Seal thickness
 Weight of the capsule fill and its variation from capsule-to-capsule
 Weight of the capsule shell and its variation from capsule-to-capsule
 Moisture level of the capsule shell before and after drying
 Visual inspection, fill weight, and fill-weight uniformity are the key
inprocess tests used for hard gelatin capsules.

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2)FINISHED PRODUCT QUALITY CONTROL TESTS:
1)Permeability and sealing
 Soft gelatin capsules are tested for physical integrity (absence of leakage) by
visual inspection.
 Similarly, hard gelatin capsules are tested for any breach of physical
integrity (breakage or opened cap and body).

2)Potency and impurity content

 All capsules are tested for drug content (potency, as a percent of label
claim).
 In addition, most drug products are tested for the related substances or
impurities.
 These must meet predefined specifications for a batch to be acceptable.

3)Average weight and weight variation

 For Hard gelatin capsules,Ten hard gelatin capsules are usually weighed
individually and the contents are removed.
 The emptied shells are individually weighed and the net weight of the
contents is calculated by subtraction.
 The content of active ingredient in each capsule may be determined by
calculation based on the percent drug content in the formulation for high
drug load formulations.
 For soft gelatin capsules, the gross weight of 10 gelatin capsules is
determined individually. Then each capsule is cut open, and the contents
are removed by washing with a suitable solvent (that dissolves the fill but
not the shell).
 The solvent is allowed to evaporate at room temperature, followed by
weighing of the individual washed shells.
 The net contents are calculated by subtraction and the content of active
ingredient in each of the capsules can be determined by calculation based
on the percent drug content in the formulation.
 Fill-weight variation of capsules is often a function of equipment setup and
filling operation. An automated capsule sizing machine and/or weight
checker is frequently used to discard over- or underfilled capsules.

4)Uniformity of content
 Uniformity of content of the active ingredient can be determined by weight
variation of the fill of hard or soft gelatin capsules for high drug load (API
≥25% w/w of the total fill weight), high fill-weight (250 mg/capsule)
formulations.
 For low drug load and low fill-weight formulations, each capsule must be
analyzed individually by the potency method for the content of the active
ingredient.
 The uniformity of content is assured if predetermined criteria for the range
and variation in the content of the active ingredient are met.

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5)Disintegration
 Disintegration of hard and soft gelatin capsules is evaluated to ensure that
the drug substance is fully available for dissolution and absorption from the
GI tract.
 The disintegration media varies depending on the type of capsules to be
tested.

6) Dissolution
 Drug absorption and physiological availability depend on the drug
substance being in the dissolved state at the site of drug absorption, viz. the
GI fluids.
 The rate and extent of dissolution of the drug from the capsule dosage form
is tested by a dissolution test.
 Dissolution test provides meansof quality control in ensuring that (a)
different batches of the drug product have similar drug release
characteristics and (b) that a given batch has similar dissolution as the
batch of capsules that was shown initially to be clinically effective.

7)Moisture content
 Water content of the entire capsule or the capsule contents are determined
by Karl Fisher titrimetry to enable the correlation of water content with the
degradation profile or drug-release characteristics of capsules.

8 )Microbial content
 The capsules are tested to ensure lack of growth of bacteria and mold by
microbiological tests.
 These tests are usually carried out by incubation of the capsule contents in
a growth medium and counting the colonies formed after a predefined period
of time.
 Selection of the growth medium and duration of the test, as well as
maintenance of aseptic conditions during the testing, are critical to
successful assessment of microbial contamination by this method.

3)SHELF-LIFE TESTS:
 Stability testing of capsules is performed to determine the physicochemical
stability of the active drug molecule in the finished drug product under
specified package and recommended storage conditions.
 Shelf-life tests are usually same as the finished product tests.
 Since the shelf life of the product at recommended storage conditions can be
long, the product is often subjected to accelerated (higher than normal levels
of environmental conditions) storage for predicting shelf life under
recommended storage conditions.
 These storage conditions that are accelerated for stability testing include
temperature, humidity, and light

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