Capsule

1. 1
UNIT-III Capsules:
a. Hard gelatin capsules: Introduction, Production of hard gelatin
capsule shells, size of capsules, Filling, finishing and special techniques
of formulation of hard gelatin capsules, manufacturing defects. In
process and final product quality control tests for capsules.
b. Soft gelatin capsules: Nature of shell and capsule content, size of
capsules, importance of base adsorption and minim/gram factors,
production, in process and final product quality control tests. Packing,
storage and stability testing of soft gelatin capsules and their
applications. Pellets: Introduction, formulation requirements,
pelletization process, equipments for manufacture of pellets

2. CAPSULES
Introduction :
Capsules are unit solid dosage form in which the drug or mixture of drugs are enclosed in
either a hard or soft, soluble container or a water soluble shell which is made from gelatin.
The capsules are available both as hard gelatin capsule and soft gelatin capsule. In addition
there are enteric coated capsules, Sustained release capsules, rectal capsules and vaginal
capsules.

3. •Hard gelatin and soft gelatin capsules are routinely used.
•Capsules are also called as hard shell (hard gelatin) capsule and
soft-shell (soft gelatin) capsule.
•Any type of formulation may be dosed into hard capsules like
blends or granules, coated pellets etc.

4. 4
Advantages of capsules:
1. The drugs having unpleasant odour and taste can be masked by enclosing them in a
shell.
2. They are smooth & become very slippery when moist, hence easily swallowed.
3. They are economic.
4. They are easy to handle and carry.
5. Capsules release the medicament as and when desired in gastro-intestinal tract.
6. Capsules are less bulky and easy for transportation.
7. They are elegant.
8. Capsules are available in various sizes & shapes.
9. Micro-capsulation provides the sustained released dosage form.
10. Solid, liquid as well as semisolid medicaments are administered by using
capsules.

5. 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.
3. Alcoholic preparations are not given in the form of capsules.
5

6. 6
Differentiation between Hard Gelatin Capsules & Soft Gelatin Capsules
Hard gelatin capsules Soft gelatin capsules
1. The hard gelatin capsule shell
consists of two parts: Body & Cap
1. The soft gelatin capsule shell becomes
a single unit after sealing the two halves
of the capsules.
2. They are cylindrical in shape. 2. They are available in round, oval
and tube like shapes.
3. It is used to administer solid
medicaments.
3. It is used to administer semisolid &
liquid medicaments.
4. These are prepared from gelatin,
titanium dioxide, coloring agent
and plasticizer.
4. These are prepared from gelatin,
plasticizer (Glycerin or Sorbitol) and
a preservative.
5. Filling & sealing are two different steps. 5. Filling & sealing takes place at a time.
6. Hand operated, semiautomatic, automatic
capsule filling machine is used for filling.
6. Rotary die machine is used for filling &
sealing.

7. Hard Gelatin Capsule
• Also called as HGC.
• Before use, the two halves are separated, the capsule is filled with powder or normally pellets and
the other half of the capsule is pressed on.
Production/ Formulation of Hard Gelatin Capsule Shells
Gelatin is the most important constituent of capsule, but other components are also present
to impart desired characteristics such as---
1. Gelatin :
• Pork, beef/ calf skin and crushed/ dry bone is used prepare HGCs.
• There are two basic types of gelatin.
• Type A, manufactured from pork skin, is derived from acid treated precursor that exhibits an
iso-electric point at pH 9.0.
• Type B, manufactured mainly from animal bones, is derived from alkali treated precursor that
exhibits an iso-electric point at pH 4.7.
• It contains up to 15% glutamic acid as a preservative.
• Gelatin is a mixture of peptides and proteins produced by partial hydrolysis of collagen.
• It melts upon heating but solidifies once cooled and with water it forms a semi-solid colloid
gel.
7

8. 8

9. 2. Plasticizer:
• Additives that increase the plasticity or fluidity .
• Provides structural integrity to the gelatin so as to maintain its shape.
• The amount of plasticizers determines the rubbery texture of the capsule.
• Eg: Glycerin, sorbitol
3. Other components:
1. Water
2. Preservatives: Methyl paraben, propyl paraben
3. Colorants: FD & C, D and C colours (water soluble dye-erythrosine)
4. Opacifier: Titanium dioxide
5. Flavoring agent: Ethyl vanillin
6. Fumaric acid is added to avoid tanning of gelatin.
7. Enteric property to capsule shell: Methyl cellulose, polyvinyl alcohol and denatured
gelatin. 9

10. 10

11. 11

12. 12

13. 13

14. 14

15. 15
Size of Capsules: The approximate capacity of a capsule with respect to its
number is given in the following Table:
Capsule Number and its Approximate Capacity
Capsule
number
Approximate capacity
in mg
000 950
00 650
0 450
1 300
2 250
3 200
4 150
5 100

16. 16
Ordinary capsule (left), a Coni-Snap capsule (center) and a DBcaps capsule
(right). In Coni-Snap and DBcaps capsules, the tapered rim of the body is
designed to avoid telescoping, the grooves on cap and body lock together; the
presence of indentations prevents premature opening.
Cap
Body

17. 17
Filling of Capsules:
• Capsule filling is a complex process
•Product to be encapsulated to ensure mass uniformity.
•The choice of capsule size and fill weight is dictated by the unit dose
requirements and the formulation to be used.
•Once this is finalized, it is easy to define the most appropriate capsule size.

18. 18
Capsule filling methods:
1.Manual filling
2.Hand filling machine
3.Semi-automatic machine
4.Fully automatic capsule filling machine

19. 19
1.Manual filling
• Filling operation begins with trituration of the ingredients to fines.
• The powder is placed on a paper and mixed with spatula for uniform
distribution.
• These materials are filled in a capsule after appropriate weighing.
• The filled capsule is tapped so that no air spaces are visible within the contents.
• Powder is added or removed from capsule body until the correct weight has
been placed in the capsule.
• The cap is then placed on body to close the capsule.
• Each filled capsule is weighed using an empty capsule as a counterweight.
• Methods are classified punch method, volume fill method, tamping method
and wax filling method.

20. 20
Methods of filling the hard gelatin
capsules:
The capsules can be filled either
by hand or by a semi-automatic device
or by an automatic filling machine.
Hand operated Capsule filling
machine:
Construction: It consists of
1. A bed having 200-300 holes
2. A loading tray having 200-300 holes
3. A powder tray
4. A pin plate having 200-300 pins
5. A sealing plate having a rubber top
6. A lever
7. A cam handle

21. 21

22. 22
After pressing, the pin plate is raised and the remaining powder is filled into the bodies of
the capsules.
The powdered tray is removed after its complete filling.
The cap holding tray is again placed in position.
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 300 holes, about 7500 capsules can be filled in one hour.

23. 23
(2) Semi-automatic capsule filling machine:
• Machine consists of capsule orientation, powder filling and capsule closing
stations.
i. Capsule orientation: capsule feeding, capsule aligning and insertion of
capsule body into bores of holding ring.
• A vacuum is used for separating capsule cap and body.
• After orientation capsule cap can stay in upper holding ring and capsule
body can stay in lower holding ring.
ii. Powder filling: Powder is filed into the body.
• Upon separation of body and cap the lower (body) holding ring is kept on
the rotary table.
• The Capsules powder is poured from the hopper over the lower (body)
• Powder hopper starts to operate and fills powder into the capsule body.

24. 24
3. Capsule closing station:
•Both the upper holding ring and lower holding rings are put together with the position that
holding ring is in front of peg ring.
• The closing plate is pivoted to a position approximately at180°.
• The pneumatic pressure is applied to peg ring which pushes capsules inside the bores of
holding ring to remove filled and sealed capsules and the finished capsules are collected
into the container.

25. 25
3. Automatic capsule filling machine:
• Use to fill hard gelatin capsules with powder or pellets are extremely sturdy
and reliable to fill dosages to highest accuracy.
• facility to provide protection against the electrical impact to prevent any
damage.
• They stop automatically in the event of improper operation.
• They have dual capsule-opening design to ensure opening of all capsules.
• The spiral feeding arrangements in the hopper ensures proper powder feeding
and filled quantities.
• Generally, they are capable of filling 6 capsules at a time with operation from
10 stations.
• Machines include accurate operation for capsule orientation, opening, filling,
joining and ejection.

26. 26
• The parts of this equipment are standard and made by computer machine.
• They are easy to replace in the event of breakdown.
• The adjustable compression piston adjusts the powder volume.
• It has an dosing tube system and the temperature control.
• Automatic vacuum removes the air from the dosing tube to give accurate
weight of the filled capsules.
• The safety sensing system shuts the machine down automatically in the event
of problems.
• These 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 1,65,000 capsules and greater per
hour.

27. 27
Cleaning of capsules:
All capsules, whether they have been filled by hand or machine, will
require cleaning. Small quantities of capsules can be wiped individually with soft
cloth. But in case of large quantities, capsules are rotated or shaken with
crystalline sodium chloride. The capsules are then rolled on cloth covered
surfaces.
Sealing of capsules:
The capsules are then sealed, to ensure that the medicaments may not
come out of the capsule due to rough handling. This can be done by banding
them with molten gelatin, laid around the joint in a strip and dried. Capsules can
be sealed by spot welding, by means of a heated metal pin, pressed against the
cap and fusing it to the body.

28. Soft Gelatin Capsule
Formulation:
1. Plasticizers: Plasticizers are used in the range of 20-30% to make the softgel shell elastic
and pliable(easy to bend). The most commonly used plasticizer is glycerin but frequently
sorbitol and PEG 400 are also used in combination with glycerin.
2. Water: Water is essential component of the soft gel shell that play important role in
processing during gel preparation and softgel encapsulation. It usually accounts for 30-40%
of the wet gel formulation.
3. Colorants and/or Opacifier: Colorants can be either natural or synthetic, and are used for
product elegance and identification. Opacifier is added when the fill formulation is a
suspension or to prevent photodecomposition of light-sensitive fill matrix ingredients. For
example, titanium dioxide produces an opaque shell.
4. Preservatives: Preservatives are incorporated to preserve the drug medicament from the
microbes. Methyl paraben and propyl paraben used in 0.2% concentration.
5. Flavouring agents: Flavouring agents are used to mask the taste of formulation
components. The commonly used flavouring agents are ethyl vanillin and essential oils
whereas sweetening agents such as various sugars, especially sucrose is also used.
28

29. 29
These are used for administration of liquid medicaments. Soft gelatin capsules
are available in round, oval and tube like shapes. They ae 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 like oils, suspensions, food concentrates and
ophthalmic products.
Shapes of soft gelatin capsules

30. 30
Method of filling of soft gelatin capsules:
Soft gelatin capsules are generally filled mechanically. The manufacturing
of the capsule shell and the filling of the medicament take place simultaneously.
Nowadays, a rotary machine is used for this purpose.
Rotary die machine:

31. 31
Construction & Working:
In a rotary die machine, the soft gelatin capsules are prepared and then
filled immediately with the liquid medicaments. The machine consists of two
hoppers. Liquid gelatin mixture is placed in one hopper and the liquid
medicament in the other hopper. There are two rotating dies which rotate in
opposite directions. When fluid gelatin mixture enters into the machine from the
hopper, it produces two continuous ribbons. These ribbons come over the rotating
dies from opposite directions and enter in between the dies. Thus, half shell of the
capsule is formed. At this stage the measured quantity of the medicament is filled
into it with the stroke of a pump. With the subsequent movement of the dies, the
other half of the capsule is formed. The two halves of the capsules are sealed
together by the heat and pressure of the rotating dies. The capsules formed are
washed thoroughly and dried. These rotary machines are capable of producing
between 25000 and 30000 capsules in an hour.

32. Quality Control Tests for Capsule
1. Size and shape:
In this test capsules are tested for uniformity of size and shape and compared
with the standard.
2. Unique identification markings:
Capsule surfaces may bear symbols or other unique identification markings,
for example, white cap, red body, imprinted with "Rx" on cap, etc., for better
identification. Inspect the capsule for this and if defective capsules are found, reject
such capsules.
3. Moisture permeation:
The degree and rate of moisture penetration are determined by packing the
capsule together with a colour revealing desiccant pellet, exposing the packaged
unit to known relative humidity over a specified time, observing the desiccant pellet
for colour change. Any change in colour indicates absorption of moisture. By
measuring pretest weight and protest weight of pellet the amount of moisture
permeated is calculated. 32

33. 33
4. Content uniformity test:
According to BP the content of the active ingredient in each of 10
capsules is taken at random using the method given in the monograph or by any
other suitable analytical method of equivalent accuracy and precision.
5. Uniformity of mass:
The intact 20 capsules are weighed. Individual capsule is opened without
losing any part of its shell and the contents are completely removed. The weight
of the contents is the difference between the initial weight and the weight of
shell.
6. Disintegration test:
To test for disintegration time, one capsule is placed in each tube of
disintegration test apparatus. Capsules comply with the test, if disintegrate, and
all particles pass through the 10 mesh screen within the time specified. For hard
capsule 30 minutes & for soft capsule 60 minutes.

34. 34
7. Dissolution test:
The USP or BP dissolution test apparatus (Basket type) is used to
determine amount of drug released. A single capsule is placed in the apparatus,
and the apparatus is operated at the specified rate. Within the specified time
interval, or at each of the times stated, a specimen sample is withdrawn and
analyzed using a suitable assay method as directed in the individual monograph.
The capsule will passes the dissolution test if the amount of drug in the solution
dissolved is not less than 70% of stated amount given in the monograph.
8. Uniformity of weight test / weight variation test:
For uniformity of weight test 20 capsules are selected randomly. If 20
capsules are not available at least 10 capsules are used for the test. Average
weight of capsule is calculated by weighing all the 20 capsules. Depending upon
the average weight of capsules, I.P. given percentage deviation in the weight of
capsules. The capsule should comply to the uniformity of weight test as per I. P.

35. 35
SR. NO.
AVERAGE WEIGHT OF
CAPSULES
%
DEVIATION
1 Less than 300mg 10%
2 300mg or more 7.5%
The capsule will passes the weight variation test when not more than two
capsule should fall outside the limit when 20 capsules are taken and one capsule
should fall outside the limit when 10 capsules are taken for test.