Hard gelatin capsules

1.  Mr Nandakishor B Deshmukh
 Assistant Professor
 Department of Pharmaceutics
 Shraddha institute of Pharmacy, kondala zambre, washim
CAPSULES
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2. CAPSULES
Introduction
 Capsules are solid dosage forms in which one or more medicinal and inert
ingredients are enclosed in a small shell or container (usually of gelatin).
 They are of various shapes and sizes and contain a single dose of one or more
active ingredients.
 They are intended for oral administration. Capsules are also defined as
“gelatin or methylcellulose shell designed to hold solids and liquids for oral
administration
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3. *There are two types of capsules, i.e., hard and soft. The hard capsule
is also called two piece as it consists of two pieces in the form of small
cylinders closed at one end.
 The shorter piece is called the cap which fits over the open end o f
the longer piece, called the body.
 Hard capsules are intended to contain solids . The soft gel atin
capsule is also called as one piece and is intended to hold liquids.
 Capsules are available in many sizes to provide dosing flexibility.
 Unpleasant drug tastes and odours can be masked by the tasteless
gelatin shell.
 Capsules are solid preparations with hard and soft shells of various
shapes and capacities, usually containing a single dose of active
ingredients.
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4. Types of Capsules
Hard Gelatin Capsules
A base containing plasticiser and water is utilised to
manufacture hard capsules. Preservatives, colours, flavours,
and s ugars may also be present in the base.
Soft Gelatin Capsules
A liquid gelatin is utilised to manufacture soft capsules or
liquid gel caps. The liquid gelatin is later hardened in a humid
environment. Generally, these capsules are a continuous piece
of gelatin.
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5. Advantages
 The advantages of capsules are:
 They are tasteless, odourless, and can be easily administered.
 They are attractive in appearance.
 The drugs having unpleasant odour and taste are enclosed in a
tasteless shell.
 They can be filled quickly and conveniently, therefore, the
physician can change the dose and combination of drugs to suit
the individual patient (this is an advantage over tablets).
 The solubility of gelatin at gastric pH provides rapid release of in
the stomach.
 They are economical.
 They are easy to handle and carry.
 They require minimum excipients.
 Little pressure is required to compact the material.
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6. Disadvantages
 The disadvantages of capsules are:
 The hygroscopic drugs are not suitable for filling into capsules as
they will absorb the water present in capsule shell, rendering the
shell very brittle and ultimately leading it to crumble into pieces.
 The concentrated solutions which require previous dilution are
unsuitable for capsules because if administered as such it will
lead to stomach irritation.
 The capsules are not suitable for highly soluble substances like
potassium chloride, potassium bromide, ammonium chloride, etc.
 They are also not suitable for highly efflorescent or deliquescent
materials.
 They demand special storage conditions.
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7. HARD GELATIN CAPSULES
 Introduction
 Hard capsules have a rigid shell in two separate pieces fitted together,
hence are also called two-piece capsules .
 There was a time when two -piece capsules could be filled only with dry
powders; but over the time, the manufacturers began filling capsules
with pellets, granules, pastes, and liquids.
 Since hard capsules can be filled with substances in a variety of forms,
they are believed to be more versatile than soft gels.
 The material types which can be filled into hard gelatin capsules are:
 1)Dry Solids: Powders, pellets, granules, or tablets.
 2)Semi-Solids: Suspensions or pastes.
 3)Liquids: Non-aqueous liquids.

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8. Size of Capsules
 Hard gelatin capsules are available in various sizes,
designated by numbers from 000 to 5. Relative sizes
of hard gelatin capsules are shown in the table.
 The exact capacity of any capsule varies according to
the density and compressibility of the formulation.
Relative amounts of water, aspirin, and sodium
bicarbonate which can be filled in capsules of
different sizes are compared in
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9. Size of Capsules
Capsule Size Water Volume (in ml) Approximate Weight (mg)
Aspirin Sodium Bicarbonate
000 1.37 1000 1430
00 0.95 650 975
0 0.68 500 715
1 0.50 320 510
2 0.37 250 390
3 0.30 200 325
4 0.21 150 260
5 0.13 100 130
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10. For small scale preparation, manual filling
machines are available in the capacities of
24, 36, 96, 100, and 144 capsules, e.g.,
hand-operated capsule filling machine.
The sizes of hard gelatin capsules intended
for human consumption are shown in
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11. Formulation of Gelatin Shell
Gelatin shell contains:
*Gelatin (main ingredient)
*Plasticizers
*Opacifying agents
*Coloring agents
*Flavouring agents
*Sweetening agents
*Preservatives
*Water and Acids.
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12. Gelatin: Gelatin is a heterogenous
product derived by irreversible hydrolytic
extraction of treated animal collagen.
Properties of gelatin depend on:
*Parent collagen,
*Method of extraction,
*pH value,
*Thermal degradation,
*Electrolyte content
Sources of Gelatin:
*Animal bones,
*Frozen pork skin,
*Hide portion
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13. .
.
Types of Gelatin:
Type A: It is derived from acid treated precursor. This type of gelatin possesses
an isoelectric point in region of pH 9.0.
Type B: it is derived from an alkali treated precursor of bones. This type of
gelatin possesses an isoelectric point in the region of pH 4.7.
Plasticizers: It increases the plasticity of the film. E.g. glycerine, sorbitol,
propylene glycol
Colouring Agents: These are used to impart colour to body and cap. E.g.
water soluble dyes, certified lakes and vegetable colours. They are used either
alone or in combination.
Opacifying agents: These are used to give opacity to the gelatin film. E.g.
Titanium dioxide.
Flavouring agents: These are used in a concentration not more than 2%. E.g.
ethyl vanillin, essential oils.
Sweetining agents: E.g. Sugar not more than 5%.
Preservatives: E.g. methyl paraben, potassium bisulphite.
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14. Formulation of Capsule Content
Glidants: e.g. talc, magnesium stearate, colloidal silica.
Fillers (diluents): e.g. lactose, starch, dicalcium
phosphate.
Disintegrants: e.g. crosspovidone, crosscarmalose
sodium.
Surfactants: e.g. sodium lauryl sulphate, sodium
socusta.
Hydrophilic agents: e.g. methyl cellulose, hydroxyl
ethyl cellulose
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15. Manufacturing of Hard Gelatin Capsule
Shell
*Dipping:
*Rotation
*Drying:
*Stripping
*Trimming
*Joining:
*Sorting:
*Printing:
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16. Filling of Hard Gelatin Capsules
Rectification: The empty capsules are oriented so that all point to the same
direction, that is, body end downward. In general, the capsules pass one at a time
through a channel just wide enough to provide a frictional grip at the cap end.
Separation of caps from bodies: This process also depends on the difference in
diameters between cap and body portions.
Dosing of fill material: Various methods are employed, which are described
below.
Filling (dosing of material) can be done by:
Auger fill principle (Gravitational forces)
Vibratory fill principle (Overfill/Scrape-off excess)
Piston tamp principle (Pressured measured):
Again there are two types of fillers:
Dosator machine, and
Dosing disc machine.
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17. Replacement of caps and ejection of filled
capsules: The cap and body bushing portions
are rejoined. Pins are used to push the filled
bodies up into the caps for closure, and to
push the closed capsules out of the bushings.
Compressed air also may be used to eject the
capsules
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18. Hand-Operated, Semi-Automatic, and Automatic
Equipments
The machines for capsule manufacturing may be hand
-operated, semi -automatic, or automatic. The various
machines used in manufacturing of hard gelatin
capsules are
Hand-Operated Capsule Filling Equipment: It
consists of (figure 4.5):
A bed having 200-300 holes,
A loading tray having 200-300 holes,
A powder tray,
A pin plate having 200-300 pins,
A sealing plate having a rubber top,
A lever, and
A cam handle.
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19. Cam
handle
Pin plate
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20. The operating steps are:
*The empty capsules are filled in the loading tray and placed over the bed.
*The cam handle is operated to separate the capsule caps from their bodies.
* The powder tray is placed in a proper position and filled with an accurate
quantity of powder with scraper.
* The excess of powder is collected on the platform of the powder tray.
* The pin plate is lowered and the filled powder is pressed by moving the pin
downwards.
* After pressing, the pin plate is raised and the remaining powder is filled into
the capsule bodies.
* The plate with the rubber top is lowered and the lever is operated to lock the
caps and bodies.
* The loading tray is then removed and the filled capsules are collected.
* With a 200 hole machine, about 5000 capsules can be filled in one hour,
whereas, in a machine having about 300 holes, about 7500 capsules can be
filled in one hour.
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21. Semi-Automatic Capsule Filling
Equipment:
*The capsules are transferred to the perforated capsule filling ring which is
rotated on a turntable.
*While rotating the ring is subjected to vacuum which pulls the bodies into
the lower half of the ring, leaving the caps in the upper half.
*The upper and lower halves of the capsule filling ring are separated
manually.
*This hopper contains a drill mechanism which is utilised to feed the
powder into the capsule bodies.
*The capsule cap is detached and the empty capsule body is held between
the thumb and forefinger and frequently pressed downward until it is fully
filled.
*The cap is th en replaced and the filled capsule is weighed using an empty
capsule of the same size as a tare.
*After the filling of capsule bodies, the cap and body rings are joined
together.
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22. Empty
Capsule
Separation of
Capsule Powder
Filling
Capsule
Closing
Finished
Capsule
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23. Automatic Capsule Filling
Equipment
Machines developed for industrial use
automatically separate the caps from empty
capsules, fill the bodies, scrape off the excess
powder, replace the caps, seal the capsules as
desired, and clean the outside of the filled capsules
at up to 1,65,000 capsules per hour
The automatic capsule filling process normally
involves four simple steps:
Removal of caps,
Filling of the bodies,
Replacement of caps, and
Ejection of filled capsules
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24. (lubricant)
Ingredient A Ingredient B Ingredient C Ingredient D
Ingredient E
Packaging
Figure 4.7: Filling of Capsule by Automated Method
Milling/sieving
Empty
capsule
Powder
blend
Blending
Capsule check-
weighing
system
Finished
capsules
Capsule
cleaner/
de-
duster
Capsule
inspection
screen
Rejects
Capsule filler
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25. Special Techniques of Formulation of Hard
Gelatin Capsules
 Imprinting on capsule s provides info rmation about the
company and enables product identification.
 Special purpose capsules are given a special treatment to
decrease the ir solubility. This may cause delayed absorption of
the active ingredient , facilitating enteric properties.
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26. Manufacturing Defects
 Deliquescent or Hygroscopic Powde rs: A gelatin capsule
contains water which is extracted or taken up by a hygroscopic
drug. This renders the capsule brittle, which leads to its cracking.
 Addition of an absorbent (like magnesium carbonate, heavy or
light magnesium oxide ) overcomes this dif ficulty, provided the
capsules are packed in tightly closed glass capsule vials
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27. Eutectic Mixtures: Certain substances when mixed
together tend to liquefy or form a pasty mass due to the
formation of a mixture having a melting point lower than
the room temperature.
Addition of Inert Powders : When quantity of the drug to
be filled in capsules is very small, an inert substance or a
diluent is added to increase th e powder bulk, thus,
facilitating easy filling of capsules.
Use of Two Capsules : Some manufacturers separate
incompatible ingredients of the formulation by placing one
of the ingredients in smaller capsule, and then placing this
smaller capsule in a largercapsule containing the other
ingredients of the formulation
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28. *Filling of Granular Powder : Powders lacking adhesiveness and
most of the granular powders are difficult to fill in the capsules by
punch method. This is because they are not compressible and flow out
of the capsule as soon as they are lifted from the powder pile into which
they are punched. To overcome this difficulty
the non-adhesive powders should be moistened with alcohol and
the granular powders should be reduced to powder before filling into
capsules.
*Improper Flow of the Powder Mixture during the Filling
Operation: Addition of suitable quantities of glidants or lubricants is
helpful in improving the flow properties of the powder mixture.
*Segregation and Homogeneity: Generally, semi -automatic or
automatic machines performing capsule filling operation may face this
error. The segregation and inhomogeneity of the particles may occur as
a result of vibrations generated by these heavy-duty machines.
Utilisation of powder having
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29. Manufacturing Defects
 Incompatibility: This defect may occur as a result of incompatibility among formulation
ingredients, formulation components, and the capsule shell. A thorough understanding of physical
and chemical properties of each ingredient is needed to prevent such defects. The excipients
generally used in the fillingof hard gelatin capsules are:
 Diluents: Lactose, corn starch, and microcrystalline cellulose are the diluents used to
increase the powder bulk and thus to facilitate its easy and accurate handling during filling
operations.
 Disintegrants: Corn starch, microcrystalline cellulose, sodium starch glycolate, and
croscarmellose are the disintegrants used for breaking down the powder bulk exposed to a
liquid medium.
 Glidants: Colloidal silicon and talc are the glidants used to improve the powder flow by
reducing the inter-particle attraction and preventing agglomeration.
 Lubricants: Magnesium and other metallic stearates are the lubricants used to minimise the
contact between powder particles and components of the filling machine.
 Surfactants: Sodium lauryl sulphate is employed into the powder mixture to reduce the surface
tension and promote powder wetting with the discharge medium containing greater quantities of
hydrophobic constituents
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30. In-Process and Final Product Quality
Control Tests
1) Appearance, 2) Size and shape,
3) Unique identification markings, 4) Assay,
5) Content of active ingredients, 6) Content uniformity test,
7) Uniformity of mass, 8) Mass variation test,
9) Disintegration test, 10) Dissolution test, and
11) Moisture permeation test.
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