CAPSULE AND ITS TYPES. MANUFACTURING PROCESS. TESTS FOR CAPSULES

1. CAPSULE
IMRAN BAKSHI
3-7-2017

2. CAPSULES
INTRODUCTION
Capsules are solid dosageforms in which one or more medicinal/inert substances
are enclosed within a water soluble small shell or container generally prepared
from suitable form of gelatin.
Capsule is the most versatile of all dosageforms. In the manufacture of
pharmaceuticals, encapsulation refers to a range of dosageforms—techniques used
to enclose medicines—in a relatively stable shell known as a capsule, allowing
them to, for example, be taken orally or be used as suppositories. The two main
types of capsules are:
1. Hard gelatin capsules
2. Soft gelatin capsules
3. Modified-release capsules
Administration – Usually orally for both HGC & SGC. HGC are formulated at
least 10 times more than SGC.
Advantages of Capsules:
1. Better bioavailability expected than tablet because they release drugs rapidly
& is not compacted.
2. They are much more flexible to formulate compared to tablet – they are
easily compounded, there is no need to form a compactresistant to handling,
unique mix fills is possible, they have important roles in drug development &
clinical trial phases (as drug can be administered W/O any additives)
3. They provide good barriers to atmospheric 02.
4. They are elegant, hence more patient compliant.

3. 5. They are portable dosage form.
6. They provide a smooth, slippery, easily swallowed & tasteless shell for
drugs.
7. They can make any drug administrative as tasteless & odorless dosage form.
8. They can be economically produced in large quantities, & in wide range of
colors.
DisadvantagesofCapsules:
1. Capsules may be difficult to formulate with very bulky materials as size is
limited.
2. Capsules filling equipment is slower than tableting equipment.
3. They are more costly than tablet; however, this should be judged on a case-
by-case basis, tablet may be more expensive also.
4. There is concern over maintaining propershell moisture constant. Usually,
shell moisture content 13-15% W/W & should be stored (unprotected) at a relative
humidity of 45-65%. It is too dry; it will become brittle/easily fractured. If too
damp, they becomesoft and sticky. Also, highly hygroscopic
drugs/efflorescent/deliquescent material may be quite difficult to formulate, as they
may softer/make the shell brittle respectively.
5. Cross linking of gelatin may occurby reacting c the contents leading to
change in flexibility of the shell & its reduced solubility.
6. Highly soluble salts (KCl, KBr, NH4Cl) should not be administered in
capsules, as their rapid release cause gastric irritation due to localized high
concentration.
7. Suppliers of shell may be limited.
8. HGC (& also tablet) may get lodged in the esophagus & may have
consequential problems.

4. GELATIN
Gelatin is heterogeneous productderived by hydrolytic extraction of animal's
collagen.
The sources of gelatins including animal bones, hide portions and frozen pork skin.
TYPES OF GELATIN
TYPE A
Derived from acid treated precursorthat exhibits an iso electric point at pH-9. It is
manufactured mainly from pork skin.
TYPE B
Derived from alkali treated precursor that exhibits an iso electric point at pH-4.7. It
is manufactured mainly from animal bones.
IMPORTANT SPECIFICATIONS OF GELATIN
BLOOM STRENGTH
• Measure of firmness.
• It is defined as the weight in grams required to depress a standard plunger 4
mm deep into the surface of a 6.67% w/w gelatin solution under standard
conditions.
• Range for hard gelatin- 200-280g.
VISCOSITY
• Controls the thickness of the film.
• Measured on a standard 6.67% w/w solution at 60˚C in a capillary pipette
and is generally in the range of 30-60 mill poise.

5. PLASTICIZER
 The plasticizer are more common for soft gelatin capsules.
 The ratio of dry plasticizer to dry gelatin determines the hardness of the
gelatin shell.
 For hard gelatin capsules ratio of glycerin/dry gelatin is 0.4/1.
 The ratio of water to dry gelatin can vary from .7 to1.3 (water) to 1.0 (dry
gelatin).
 In most formulations it is approximately 1 to 1.
Iron content:
Iron is always presentin raw gelatin, and its concentration usually depends on the
iron content of the large quantities of water used in its manufacturing.
 Amount should not exceed 15ppm.
Hard gelatin capsules
Hard capsules have shells consisting of two cylindrical sections. The active
ingredient or ingredients, usually in solid form (powder or granules) are filled into
one of the sections which is then closed by slipping the other section over it.
Shell composition of hard gelatin capsules: The hard gelatin capsule consists of
two pieces in the form of cylinders closed at one end. The shorter piece is called
the cap. This cap fits over the open end of longer piece called body. contain 12 - 16
% moisture.
 typically filled with dry solids
 powders
 granules
 pellets

6.  tablets
Gelatin is the most important constituent of the dipping solutions, but other
components may also be present.
i. Colorants
ii. Opaquing agent
iii. Preservatives
iv. Water
Steps in HGC shell manufacture:
A. DIPPING: Pairs of SS pins dipped into a solution of gelatin to
simultaneously form cap & bodyof the capsules. Pins at ambient
temperature (22 degree 0C), lubricated c a patented mold release agent, is
dipped in dipping solution maintained at 50 degree 0C. Film casting time
is approx. 12S but increase c size capsules.
B. ROTATION: After dipping pins are withdrawn from dipping solution,
elevated & rotated 2.5 times until they face upward. The rotation
distributes gelatin uniformly over the whole pin surface giving uniform
thickness & prevents formulation of a lead at the tip. Then a blast of cool
air sets the film.
C. DRYING: The set gelatin film coated pins then pass thru a set of 4 drying
ovens. Drying is done by dehumidification (using large quantity of dry
air) & a few degree rise in temperature (excess temp would melt the
shells). Rapidly drying should be avoided to prevent case-handling. Over
drying would cause film-cracking/brittleness (due to shrinkage). Under
drying cause a too pliable.
D. STRIPPING:Pairs of bronze jaws (softer than SS) strip the cap & body
of capsules from the pins.
E. TRIMMING: The two parts are firmly held in a rotating collect & a knife
trims the shells to accurate size.
F. JOINING: The cap & bodyare aligned & joined concentrically in
channels by slowing pushing then together.

7. G. SORTING: Immediately prepared capsules have a moisture content of
15-18% W/W. The final adjustment to moisture content occurs during
sorting step. In the step the defective shells are sorted out & discarded.
H. PRINTING: In some cases, capsule shells may be printed before filling
due to faster handling & since loss. Printing is done on offset rotary
presses output rates as high as 0.75 million/hr. Printing is done either
axially or radially on the shells.
Finished capsules are pushed onto a conveyer belt which carries them out to a
container.
Capsule quality is monitored throughout the production process including size,
moisture content, single wall thickness, and colour.
Capsules are sorted and visually inspected.
Capsule size
For human use, empty capsules ranging in size from 000 the largestto 5 the
smallest. Generally, hard gelatin capsule are used to encapsulate between 65 mg to
1 gram. The standard shape of capsules is traditional, symmetrical and
bullet shape.
Capsules of the size No. 5 to No. 0 generally are not too difficult to swallow. Many
patients may have difficulty swallowing the No. 00 and No. 000 capsules. If this
occurs, the patient may be advised to place the capsule on the back of the tongue
before drinking a liquid, or to place the capsule in warm water for a few seconds
prior to taking to make it slide over mucous membranes easily. The pharmacist

8. may suggest an alternative dosage form, e.g. smaller capsules or a liquid or rectal
preparation.
Filling hard capsule shells
The process ofworking:
 Rectification
 Separating the caps from empty capsules
 Filling the bodies
 Scraping the excess powder
 Replacing the caps
 Sealing the capsules
 Cleaning the outside of the filled
capsules
 160,000 capsules per 8hour shift
FILLING OF HARD GELATIN CAPSULES
Various Filling Machine Available…
 Eli-lily and Co
 Farmatic
 Hofliger and Karg
 Zanasi
 Parke-Davis.

9. These machine differ in their design and output.
SOFT GELATIN CAPSULE
Definition: -
Soft Gelatin capsules are one piece, hermetically sealed, soft gelatin shells
containing a liquid, a suspension, or a semisolid.
Soft gelatin is mainly composed ofgelatin, plasticizers, preservative, coloring and
opacifying agents, flavoring agents and sugars.
APPLICATION OF SOFT GELATIN CAPSULE:
The pharmaceutical applications of softgelatin capsules are:
- as an oral dosage form
-as a suppositorydosage form
-as a specialty package in tube form, for human and veterinary use, single
doseapplication for topical, ophthalmic, and rectal ointments.
SHAPE OF CAPSULE
The shape of soft gelatin capsules are round, oval, oblong, tube.
MANUFACTURING SOFT GELATIN CAPSULES
1.Composition ofthe shell
-The basic component of soft gelatin shell is gelatin; however, the shell has been
plasticized.
-The ratio of dry plasticizer to dry gelatin determines the “hardness” of the shell
and can vary from 0.3-1.0 for very hard shell to 1.0-1.8 for very softshell
-Up to 5% sugar may be included to give a “chewable” quality to the shell
-The residual shell moisture content of finished capsules will be in the range of 6-
10%.

10. II. Plasticizerand Gelatin ratio
-In soft gelatin capsule the amount of plasticizers used is more
-In soft gelatin capsule the plasticizer and gelatin ratio is
0.8:1
-In hard gelatin capsule the plasticizer and gelatin ratio is
0.4:1
III. Formulation :
-Formulation for softgelatin capsules involves liquid, rather than powder
technology.
-Materials are generally formulated to producethe smallest possible capsule
consistent with maximum stability, therapeutic effectiveness and manufacture
efficiency.
-The liquids are limited to those that do not have an adverse effect on gelatin walls.
-Emulsion cannot be filled because water will be released that will affect the shell
-The pH of the liquid can be between 2.5 and 7.5.
MANUFACTURE OF SOFT GELATIN CAPSULES
Is manufactured by four methods
1.Plate process
2.Rotary die process
3.Reciprocating die
4.Accogel machine
Plate process
-Place the gelatin sheet over a die plate containing numerous die pockets.

11. -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.
Rotary die press
-In this machine the soft gelatin capsules are prepared & then filled immediately
with liquid medicaments it is having two hoppers & two rotating dies.
- Liquid mixture is placed in one hopper & the liquid medicament in other Hooper.
- The two rotating dies rotate in opposite directions when the fluid gelatin mixture
enters the machine from the hopper it produces two continuous ribbons.
-These half shell of the capsule is formed.
-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.
-The two halves' of the capsules are sealed together by the heat & pressure of the
rotating dies.
-As the die rolls rotate, the convergence of the matching die pockets seals and cuts
out the filled capsules

12. Quality control of capsules:
Whether capsules are produced on a small scale or large scale all of them are
required to pass not only the disintegration test, weight variation test and
percentage of medicament test but a visual inspection must be made as they roll off
the capsule machine onto a conveyor belt regarding uniformity in shape, size, color
and filling. As the capsules moves in front of the inspectors the visibly defective or
suspected of being less than the perfect are picked out. The hard and soft gelatin
capsules should be subjected to following tests for their standardization.
1. Shape and size
2. Color
3. Thickness of capsule shell
4. Leak test for semi-solid and liquid ingredients from softcapsules
5. Disintegration tests
6. Weight variation test

13. 7. Percentage of medicament test
In official books the following quality control tests are recommended for
capsules:
1) Disintegrationtest: Forperforming disintegration test on capsules the tablet
disintegration test apparatus is used but the guiding disc may not be used except
that the capsules float on top of the water. One capsule is placed in each tube
which is then suspended in the beakers to move up and down for 30 minutes,
unless otherwise stated in the monograph. The capsules pass the test if no residue
of drug or other than fragments of shell remains on No. 10 mesh screen of the
tubes.
2) Weight variation test: 20 capsules are taken at random and weighed. Their
average weight is calculated, then each capsule is weighed individually and their
weight noted. The capsule passes the test if the weight of individual capsule falls
within 90-110% of the average weight. If this requirement is not met, then the
weight of the contents for each individual capsule is determined and compared
with the average weight of the contents. The contents from the shells can be
removed just by emptying or with the help of small brush. From soft gelatin
capsules the contents are removed by squeezing the shells which has been carefully
cut. The remainder contents are removed by washing with a suitable solvent. After
drying the shells, they are weighed and the content weights of the individual
capsules are calculated. The requirements are met if (1) not more than 2 of the
differences are greater than 10 % of the average net content and (2) in no case the
difference is greater than 25 %.
3) Content uniformity test: This test is applicable to all capsules which are
meant for oral administration. Forthis test a sample of the contents is assayed as
described in individual monographs and the values calculated which must comply
with the prescribed standards.
4) Capsule stability: Unprotected soft capsules (i.e., capsules that can breathe)
rapidly reach equilibrium with the atmospheric conditions under which they are
stored. This inherent characteristic warrants a brief discussionof the effects of
temperature and humidity on these products, and points to the necessity of proper
storage and packaging conditions and to the necessity of choosing an appropriate

14. retail package. The variety of materials capsulated, which may have an effect on
the gelatin shell, together with the many gelatin formulations that can be used,
makes it imperative that physical standards are established for each product.
Effect of Temperature and Humidity on Capsule shell
Temperature and Humidity Effect on Capsule shell
-At 21-24°C, 60% Capsules become softer, tackier and bloated
-Greater than 24°C, Greater than 45% More rapid and pronounced effects –
unprotected capsules melt and fuse together.
Packaging and storage of capsules.
Capsules should be packed in a well-closed glass or plastic containers and stored in
a coolplace. These type of containers have advantage over cardboard boxes that
they are more convenient to handle and transport and protectthe capsules from
moisture and dust. To prevent the capsules from rattling a tuft of cottonis placed
over and under the capsules in the vials. In vials containing very hygroscopic
capsules a packet-containing desiccant like silica gel or anhydrous calcium
chloride may be placed to prevent the absorptionof excessive moisture by the
capsules. Now days capsules are strip packaged which provide sanitary handling of
medicines, ease in counting and identification.
Empty gelatin capsules should be stored at room temperature at constant humidity.
High humidity may cause softening of the capsules and low humidity may cause
drying and cracking of the capsules. Storage of capsules in glass containers will
provide protection not only from extreme humidity but also from dust.
Storage of filled capsules is dependent on the characteristics of the drugs they
contain. Semisolid filled hard gelatin capsules should be stored away from
excessive heat, which may cause a softening or melting of the contents.

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