Chapter 3

Capsules

PRESENTED BY:
HARI KESH MEENA
LECTURER OF PHARMACEUTICS 1

G.D.MEMORIAL COLLEGE OF PHARMACY,JODHPUR

 Introduction - The definition of
capsules
Capsula “Latin word”: small box (fixed volume!)
From a pharmaceutical stand point:
Capsules are solid dosage forms in which
medicinal agents and/or inert substances are
enclosed within a small shell of gelatin.
Gelatin capsule shells may be hard or soft
depending on their composition.
Administration route of capsules
orally (whole or mixed with food or drink after
opening capsules)
2
 Introduction - The definition of
capsules
Capsules are solid dosage forms in which the drug
substance is enclosed in either a hard or soft soluble
container or shell of a suitable form of gelatin.
Steps in capsule production
1. Mixing of ingredient
2. Granulation and lubrication
3. Making of capsules
4. Filling of capsules
5. Uniformity testing
6. Packing and labeling
3
Introduction – Advantages of
capsules for oral administration
1. conveniently carried
2. readily identified
3. easily taken
4. prescribing flexibility
5. Efficiently and productively manufactured
6. Packaged and shipped at lower cost and with less
breakage
7. More stable and have a longer shelf-life
8. Empty hard gelatin capsules are often used in the
extemporaneous compounding of prescriptions.
9. Tablets and capsules are sometimes used as the
source of a medicinal agent when it is not otherwise
available.
4
 Introduction - Dosage forms that
must be left intact
Dosage forms that must be left intact include:
 enteric coated tablets: designed to pass through the
stomach for drug release and absorption in intestine
 extended/controlled release dosage forms: designed to
provide prolonged release of the medicament
 sublingual or buccal tablets: formulated to dissolve
under the tongue or in the mouth
If a patient is unable to swallow an intact solid
dosage form, an alternative product may be
employed, such as chewable tablet, instant
dissolving tablet, oral liquid, suppository or
injection. 5
 Types of capsules

Gelatin capsule shells may be hard or soft

depending on their composition.
 Hard gelatin capsules

 Soft gelatin capsules

Hard gelatin capsules: “two-piece” capsules

(body and cap).
Soft gelatin capsules: “one-piece” capsules.

6
 Hard gelatin capsules
The application of hard gelatin capsules
 used to manufacture most medicated agents
 employed in clinical trials, to compare the
effect of an investigational drugs with those of
another drug product or placebo
 used in the extemporaneous compounding

The empty capsule shells consist of

gelatin, sugar, water, colorants (various dyes),
and opaquants (titanium dioxide).
They can be clear, colorless and essentially
tasteless or they may be coloured with dyes 7
Gelatin: Nature
 Gelatin is a mixture of water soluble
proteins (Mw ranges from 20-250 kDa).
 Prepared by the hydrolysis of collagen
(protein of the connective tissues), followed
by purification, concentration and drying.
 Main sources of collagen: Animal bones
and skin.
 It is available in the form of a fine powder, a
coarse powder, shreds, flakes or sheets.
 Average molecular weight of gelatin varies
between 20,000 and 2,00,000.
8
Types of gelatin

According to the hydrolysis processing:

Two popular grade of gelatin:
Pharmagel – A and Pharmagel – B
Type A: produced by acid hydrolysis, IEP ≈
4.7 and pH 4.8 to 5.2
Type B: produced by basic (alkaline)
hydrolysis, IEP ≈ 9.0 and pH 6.5 to 9.5
A mixture of the two types or only one can be
used according to the required properties.
9
 Gelatin: Important properties
The main quality control item of gelatin
 Bloom strength (a measure of gel rigidity)

 Viscosity degradation

 Moisture content

 transparency

 ash value

 pH value

 Iron: Its concentration depends on the iron

content of the water used in its
manufacture. ≤15ppm for gelatin used in
soft gelatin capsules. 10
Gelatin as a capsule shell:
WHY?

 Non toxic
 FDA approved in food stuff!!!
(risk of disease transmission).
 Soluble in biological fluids at
body temperature.
 Good film-producing material.

 Displays thixotropic properties.

11
Hard gelatin capsules
 Capsule shell:
Gelatin Opecifier
Water Preservative
Colourants Wetting agents
 Materials to be filled (formulation):
Active ingredients Diluents (filler)
Glidants lubricants
Wetting agents Disintegrants
12
 Capsules shell: Water content
Normally, hard gelatin capsules contain between
13 to 16% of moisture.
 High % of water: softening and deformation,
microbial contamination.
 Low % of water: brittle, breakdown upon use.

 12-16 %: acts as a plasticizer.

 Very critical during manufacturing and storage.

The solubility property of gelatin:

Insoluble in cold water, soften through the absorption of
up to ten times its weight of water;
soluble in hot water and in warm gastric fluid.
Gelatin, being a protein, is digested by proteolytic 13
enzymes.
Capsule shell: Colourants
 Mainly synthetic.
 Water-soluble or water-insoluble.

 Azo- or non-azo dyes.

 Usually, a mixture is used.

 Examples: erythrosine,
indigocarmine.

14
 The manufacture of hard
gelatin capsule shells
The shell consists of two parts, the capsule body and the
capsule cap.
 The body is longer and slightly smaller in diameter than
the cap.
 Shape is mainly oblong.

The process of capsule shell production with the peg/pin

method:
dipping → drying → stripping → trimming → joining
a) The thickness of the gelatin walls must be strictly controlled.
b) The caps are slightly larger in diameter than the bodies.

15
Manufacture of Hard Gelatin Capsules
1. Shell composition :
Gelatin :
 Prepared by the hydrolysis of collagen.
 Gelatin in its chemical and physical properties,
depending upon the source of the collagen and
extraction.
 There are two basic types of gelatin:
Type – A and Type – B.
 The two types can be differentiated by their
isoelectric points (7.0 – 9.0 for type A and 4.8 – 5.0
for type B) and by their viscosity and film forming
16
characteristics.
Manufacture of Hard Gelatin Capsules
 Combination of pork skin and bone gelatin are often
used to optimize shell characteristics.
 The physicochemical properties of gelatin of most
interest to shell manufactures are the bloom strength
and viscosity.
Colorants :
 Various soluble synthetic dyes (“coal tar dyes”) and
insoluble pigments are used.
 Not only play a role in identifying the product, but also
may play a role in improving patient compliance.
E.g., white, analgesia; lavender, hallucinogenic effects;
17
orange or yellow, stimulants and antidepressants.
 Manufacture of Hard Gelatin
Capsules
Opaquing agents :
 Titanium dioxide may be included to render the
shell opaque.
 Opaque capsules may be employed to provide
protection against light or to conceal the contents.

Preservatives :
 When preservatives are employed, parabens are
often selected.
18
2) Shell manufacture :

19
I. Dipping :
 Pairs of the stainless steel pins are dipped into the dipping
solution to simultaneously form the caps and bodies.
 The pins are at ambient temperature; whereas the dipping
solution is maintained at a temperature of about 50 0C in a
heated, jacketed dipping pan.
 The length of time to cast the film has been reported to be
about 12 sec.
II. Rotation :
 After dipping, pins are elevated and rotated 2-1/2 times
until they are facing upward.
 This rotation helps to distribute the gelatin over the pins
uniformly and to avoid the formation of a bead at the
capsule ends. 20
III.Drying :
 The racks of gelatin coated pins then pass into a
series of four drying oven.
 Drying is mainly done by dehumidification.
 A temperature elevation of only a less degrees is
permissible to prevent film melting.
 Under drying will leave the films too sticky for
subsequent operation.
IV. Stripping :
 A series of bronze jaws strip the cap and body
portions of the capsules from the pins.
21
V. Trimming :
 The stripped cap and body portions are
delivered to collects in which they are firmly
held.
 As the collects rotate, knives are brought
against the shells to trim them to the required
length.
VI. Joining :
 The cap and body portions are aligned
concentrically in channels and the two portions
are slowly pushed together.
22
 The manufacture of hard
gelatin capsule shells
Some improvements to hard gelatin capsule shells
 capsule-making pegs (body-making or cap-making pegs):

general rounded shape pegs → tapered pegs

 tapered rims, indentations and locking grooves:

straight-walled capsule shell → tapered rim capsule shell with

indentations and locking grooves
a) The tapered rims avoid splitting;
b) The indentations prevent premature opening;
c) The grooves lock the two capsule parts together after the
capsule has been filled.
 extension capsule cap (CONI-SNAP SUPRO)

increase the security of the contents and the integrity of the

capsule
23
The manufacture of hard
gelatin capsule shells
Tamper-evident sealing and imprinting
 Tamper-evident sealing : through various capsule
sealing techniques
 Imprinting
which signals will be imprinted on finished capsules?
a) names and monograms of the manufacturer
b) the assigned national drug code (NDC) number
c) other markings making the product identifiable and
distinguishable from other products

24
 Capsule sizes
 How to select capsule size?
1) the amount of fill material to be encapsulated
2) the density and compressibility of the fill
3) The final determination largely may be the result of trial.
 The sizes of empty capsules
There are different sizes: from OOO (biggest) to 5 (smallest),
different filling capacity (60 mg to 1 g) depending on the
density.
For human use: 000(the largest), 00, 0, 1, 2, 3, 4, 5 (the
smallest)
For veterinary use: Larger capsules are available. 25
Capsule size and body fill
volumes
S.No. Capsule Size Body Volume Body Weight
(ml) (gm)
1. 000 1.30 1.00
2. 00 0.95 0.65
3. 0 0.68 0.50
4. 1 0.50 0.32
5. 2 0.37 0.25
6. 3 0.30 0.20
7. 4 0.21 0.15
8. 5 0.13 0.10

For veterinary use larger capsules No., 10, 11 and 12 approx

capacities of 30, 15 and 7.5 gms. are also marketed. 26
 Preparation of filled hard
gelatin capsules
 The general steps of preparation
1) developing and preparing the formulation and
selecting the size of capsule.
2) filling the capsule shells.
3) capsule sealing (optional).
4) cleansing and polishing the filled capsules.
The selection of capsule size
 For a commercial product: during the product
development stage
 In the extemporaneous compounding of prescriptions
27
 Developing the formulation and
selection of capsule size
The goal of developing a capsule formulation is to prepare
a capsule with
How to get to the goal?
1) pharmaceutical processing
2) pharmaceutical excipient
The pharmaceutical processing in the preparation of filled
hard gelatin capsules
1) blending: → uniform powder mix, uniform drug
distribution
2) comminution/milling: 50~100 microns, suitable for a
drug of low dose (10mg or greater)
3) micronization: 10~20 microns, suitable for drugs of 28
lower dose
 Developing the formulation and
selection of capsule size
The pharmaceutical excipient in the preparation of
filled hard gelatin capsules
1) Diluents/filler: to produce the proper capsule
fill volume; to provide cohesion to the powders,
e.g. lactose, microcrystalline cellulose and
starch
2) Disintegrants/disintegration agents: to assist
the break-up and distribution of the capsule
contents
e.g. pregelatinized starch, crosscarmellose ,
and sodium starch glycolate (SSG) 29
Developing the formulation and
selection of capsule size
The pharmaceutical excipient in the preparation
of filled hard gelatin capsules (continued)
3) Lubricant or Glidant: to enhance the flow properties
of the powder mix
e.g. fumed silicon dioxide, magnesium stearate,
calcium stearate, stearic acid, or talc
#: magnesium stearate, water-proofing
characteristics, retard penetration of the GI fluids,
delay drug dissolution and absorption
4) Wetting agents: to facilitate wetting of the dry powder
e.g. surfactants, as sodium lauryl sulfate

30
 Developing the formulation and
selection of capsule size
The form of filling material in capsules:
1) powder or granulate
2) pellet mixture
3) paste or wetted mass: the mixture of liquid and an inert
powder
4) capsule
5) tablet
6) liquids: fixed or volatile oils (locking or sealed gelatin
capsules)
7) eutectic mixtures: mixed with a diluent or absorbent to
separate the interacting agents and to absorb any
liquefied material
31
 Developing the formulation and
selection of capsule size
Examples of filled hard gelatin capsules
1) Tetracycline capsules
Active ingredient: Tetracycline hydrochloride, 250 mg
Filler: Lactose
Lubricant/Glidant: Magnesium stearate
Capsule colorants: omitted
Capsule opaquant: Titanium dioxide

32
 Filling hard capsule shells
For filling the hard gelatin capsule shell, there are four
methods
1. The “punch” method
2. The pouring method
3. Hand-operated capsule filling machines
4. Machines for industrial use
1. The “punch” method
suitable for filling a small number of capsules in the
pharmacy
1) placing the powder on paper
2) forming the powder mix into a cake
3) punching the empty capsule body into the powder cake
1) non potent drugs: The first filled capsules should be
weighed. The other capsules should be weighed
periodically.
2) potent drugs: Each capsules should be weighed. 33
 Filling hard capsule shells
2. The pouring method
suitable for filling a small number of capsules in the
pharmacy
suitable for granular material
3. Hand-operated capsule filling machines
Hand operated and electrically operated machines are in
practice for filling the capsules but for small and quick
dispensing hand operated machines are quite
economical.
These machine are very simple to operate, can be easily
dismantled and reassembled.

34
A hand operated hard gelatin capsule filling
machine consists of the following parts.
 A bed with 200 or 300 holes.
 A capsule loading tray.

 A powder tray.

 A pin plate having 200 or 300 pins

corresponding to the number of holes in the
bed and capsule loading tray.
 A lever.

 A handle.

 A plate fitted with rubber top.

All the parts of the machine are made up of

35
stainless steel.
Filling hard capsule shells
Hand-operated capsule filling machines
consist of a couple of plates

36
 Filling hard capsule shells

4. Machines for industrial use

The process of working:
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
165,000 capsules per hour

37
SCF-10
 Filling of hard gelatin capsules
Equipment used in capsule filling operations
involves one often of two types of filling systems.
Zanasi or Martelli encapsulator:
 Forms slugs in a dosatar which is a hollow tube
with a plunger to eject capsule plug.
Hofliger-Karg machine:
 Formation of compacts in a die plate using
tamping pins to form a compact.

38
 ZANASI AUTOMATIC HOFLIGER KARG AUTOMATIC
CAPSULE FILLING MACHINE CAPSULE FILLING MACHINE
39
In this both system, the scale-up process
involve bulk density, powder flow,
compressibility, and lubricant distribution.

Overly lubricated granules are responsible for

delaying capsule disintegration and dissolution.

40
 OSAKA MODEL R-180
SEMI AUTOMATIC CAPSULE
FILLING MACHINE
41
 Difficulties in filling the capsules
 Deliquescent and hygroscopic powders: a
gelatin capsule contains water which is extracted
or taken up by a hygroscopic drug and renders the
capsule very brittle which leads to cracking of the
capsule.
 The addition of absorbent like magnesium
carbonate or light magnesium oxide overcomes
this difficulty provided the capsules are packed in
tightly closed glass capsule vials.
 Eutectic mixtures: certain substances when
mixed together tend to liquefy or form a pasty
mass due to the formation of a mixture which has
a lower melting point than room temperature. 42
 Difficulties in filling the capsules
 The absorbents used are magnesium oxide and
kaolin.
 Another method in dealing with such type
difficulty is that the substances are mixed
together so as to form a eutectic mixtures, then
absorbent like MgCO3 or Kaolin is used
 Addition of inert powders: when the quantity of
the drug to be filled in capsules is very small and
it is not possible to fill this much small amount in
capsules then inert substances or a diluents is
added so as to increase the bulk of the powder
which can be easily filled in capsules.
43
Difficulties in filling the capsules
 Filling of granular powders: some powders
which lack adhesiveness and most granular
powders are difficult to fill in the capsule by
punch method because they are not
compressible and flow out of the capsule as
soon as they are lifted from the pile of the
powder in to which they are punched.
 To overcome this difficulty the non adhesive
powder should be moistened with alcohol
and the granular powders should be reduced
to powder before filling in to capsules.
44
Difficulties in filling the capsules
 Use of two capsules: some of the manufactures
separate the incompatible ingredients of the
formulation by placing one of the ingredients in
smaller capsule and then placing this smaller
capsule in a larger capsule containing the other
ingredients of the formulation.
 Liquids: oil and liquids which will not dissolve
gelatin may be filled into hard gelatin capsules.
 When the quantity of the liquid to be
incorporated is small, it is first mixed with an
inert absorbent which is then added to another
ingredient, mixed thoroughly and filled in to
45
capsule.
 Capsule sealing
Sealing of the caps on to bodies is possible by
moistening the upper part of the body and
slipping the cap on make the capsules tamper-
evident
1) sealing with a colored band of gelatin
2) heat welding
3) Thermally bonding at 40-45℃ with the help of
a melting-point-lowering liquid wetting agent
4) extemporaneously, by lightly coating the
inner surface of the cap with a warm gelatin
solution
46
Cleaning and polishing capsules
Small amount of powder may adhere to the
outside of capsules after filling.
1) On a small scale, cleaning with a clean gauze
or cloth.
2) On a large scale, cleaning vacuum
The following steps are involved in the
finishing process:
1. salt polishing
2. cloth dusting
3. brushing
4. inspection 47
Soft gelatin capsules
The definition of soft gelatin capsules
Manufactured in one piece in which the drug is in a
liquid form inside the soft shell
Soft gelatin capsules are made of gelatin, glycerin (or a
polyhydric alcohol such as Sorbitol) and water etc. to
hermetically seal and encapsulate liquids, suspensions,
pasty materials, dry powders and even preformed
granules, pellets, tablets. They may be manufactured to be
oblong, oval or round in shape.
The advantages of soft gelatin capsules
1) pharmaceutically elegant
48
2) easily swallowed by the patient
Soft gelatin capsules

49
 Differs from HGC in:
1. Bloom strength: less than HGC
2. Amt of water and humidity.
3. Hydrophilicity.

50
 Soft gelatin capsules
The pharmaceutical applications of soft gelatin
capsules are
1) as an oral dosage form for human or veterinary
use
2) as a suppository dosage form for rectal use or for
vaginal use
3) as a specialty package in tube form, for human
and veterinary single dose application of topical,
ophthalmic, and otic (ear) preparations, and rectal
ointments.
4) in the cosmetic industry, may be used for breath
fresher's, perfumes, bath oils & skin creams. 51
 Soft gelatin capsules
The components of soft gelatin capsules
1) gelatin
2) glycerin or polyhydric alcohol
3) water/moisture
4) preservative
5) colorant
6) markings
7) opaquants
8) Flavors may be added and up to 5% sucrose may
be included for its sweetness and to produce a
chewable shell.
52
 Manufacture of Soft Gelatin
Capsules
I. Composition of the shell:
 Similar to hard gelatin shells, 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 soft shell.
 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%. 53
Soft Gelatin Capsules

54
II. Formulation :
 Formulation for soft gelatin capsules involves
liquid, rather than powder technology.
 Materials are generally formulated to produce
the 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.
 The pH of the liquid can be between 2.5 and 7.5.
 Emulsion can not be filled because water will be
released that will affect the shell. 55
 The types of vehicles used in soft gelatin capsules
fall in to two main groups:
1. Water immiscible, volatile or more likely more volatile
liquids such as vegetable oils, mineral oils, medium-
chain triglycerides and acetylated glycerides.
2. Water miscible, nonvolatile liquids such as low
molecular weight PEG have come in to use more
recently because of their ability to mix with water
readily and accelerate dissolution of dissolved or
suspended drugs.
 All liquids used for filling must flow by gravity at
a temperature of 350c or less.
 The sealing temperature of gelatin films is 37-400C.
56
 Preparation of soft gelatin capsules
III Manufacture process :
A. Plate process :
The process involved
 Placing the upper half of a plasticized gelatin sheet
over a die plate containing numerous die pockets,
 Application of vacuum to draw the sheet in to the die
pockets,
 Filling the pockets with liquor or paste,
 Folding the lower half of gelatin sheet back over the
filled pockets, and
 Inserting the “ sandwich” under a die press where
the capsules are formed and cut out. 57
Preparation of soft gelatin
capsules
The plate process (using a set of molds)
The plates contain die pockets.
1) placing a warm sheet of gelatin on the bottom plate
2) pouring the liquid-containing medications
3) placing the second sheet of gelatin
4) putting the top plate of the mold into place
5) pressing the mold to form, fill, and seal the capsules
simultaneously
6) removing and washing the capsule
Today, this equipment can no longer be purchased.

58
B. Rotary die press:
 In this process, the die cavities are machined in to
the outer surface of the two rollers.
 The die pockets on the left hand roller form the left
side of the capsule and the die pockets on the right
hand roller form the right side of the capsule.
 Two plasticized gelatin ribbons are continuously
and simultaneously fed with the liquid or paste fill
between the rollers of the rotary die mechanism.
 As the die rolls rotate, the convergence of the
matching die pockets seals and cuts out the filled
capsules.
59
Preparation of soft gelatin capsules
The rotary die process (1933, R. P. Scherer)
more efficient and productive

1) Liquid gelatin is formed into two ribbons

2) The two ribbons are brought together
3) Metered fill material is injected between the
ribbons
4) These pockets of fill-containing gelatin are
sealed

60
Rotary die press

61
62
Rotary die soft capsule
machine The dies for production of soft
capsule
63
C. Accogel process:
 In general, this is another rotary process involving
 A measuring roll,
 A die roll, and
 A 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.
64
 Preparation of soft gelatin
capsules
The Accogel
machine (1949,
Cyanamid company)
This equipment is
unique in that it is
the only equipment
that accurately fills
powdered dry
solids.

65
66
D. Bubble method:
 The Globex Mark II capsulator produces truly
seamless, one-piece soft gelatin capsules by a
“bubble method”.

67
68
 A concentric tube dispenser simultaneously
discharges the molten gelatin from the outer
annulus and the liquid content from the tube.
 By means of a pulsating pump mechanism, the
liquids are discharged from the concentric tube
orifice into a chilled-oil column as droplets that
consists of a liquid medicament core within a
molten gelatin envelop.
 The droplets assume a spherical shape under
surface tension forces and the gelatin congeals on
cooling.
 The finished capsules must be degreased and
69
dried.
Preparation of soft gelatin capsules
E. The reciprocating die process
(1949, Norton company)
is similar to the rotary process in that ribbons of
gelatin are formed and used to encapsulate the fill,
but it differs in the actual encapsulating process.
1) A set of vertical dies continually open and close to
form rows of pockets in the gelatin ribbons.
2) These pockets are filled with the medication and
are sealed, shaped, and cut out of the film.
3) The capsules fall into refrigerated tanks which
prevent the capsules from adhering to one another.

70
IV. Soft/Liquid-filled hard gelatin capsules:
 Important reason: the standard for liquid filled
capsules was inability to prevent leakage from hard
gelatin capsules.
 As banding and of self-locking hard gelatin
capsules, together with the development of high-
resting state viscosity fills, has now made
liquid/semisolid-filled hard gelatin capsules.
 As with soft gelatin capsules, any materials filled
into hard capsules must not dissolve, alter or
otherwise adversely affect the integrity of the shell.
 Generally, the fill material must be pumpable. 71
 Three formulation strategies based on having a high
resting viscosity after filling have been described.
1. Thixotropic formulations,

2. Thermal-setting formulations,

3. Mixed thermal-Thixotropic systems.

 The more lipophilic contents, the slower the release

rate.
 Thus, by selecting excipients with varying HLB
balance, varying release rate may be achieved. 72
 The nature of soft gelatin
capsule shell
1) The gelatin is Pharmacopoeial grade with
additional specifications required by the capsule
manufacturer.
a) Bloom strength(measure of rigidity) :Load in gms
required to push a stand plunger 4mm into the gel.
 The gelatin used in HGC is of higher bloom strength
(200-250 gm) than that used for SGC(150gm)
b) viscosity:
Generally, 25 to 45 millipoise is acceptable.
c) iron: ≤15ppm
73
 The nature of soft gelatin
capsule shell
2) Plasticizers
glycerin or Sorbitol or combinations of these
The ratio by weight of dry plasticizer to dry gelatin
determines the “hardness” of the gelatin shell.
0.4/1 hard
0.6/1 medium
0.8/1 soft
The ratio by weight of water to dry gelatin can vary from
0.7-1.3 to 1.0.
3) The color of the gelatin shell

74
 Formulation of soft gel
 Gelatine: Alkali processed(Type B) 40% of gel
mass.
We can also use Type A acid gelatin.
Plasticizer:20-30% of gel mass,its amount depends
on:
1-Hardness 2- dissolution and Disintegrant.
3- Stability. 4-Compatabile with all.5- appearance.
Water:30-40% of gel mass, ensure proper
processing, excess water is removed by drying.
In dry soft gels water 5-8% w/w, thus good
stability.
Colourants and opacifier: as HGC
75
Properties of soft gelatin shells

 O2 permeability: 2-Residual H2O

 Good barrier against content:
O2 diffusion.
(little in SGC)
 O2 permeability
About 7% in shell while
decrease With %
H2O content in the fill in
relative humidity.
equilibrium with atm.
 (add glycerol for max.
Protection 30-40%) 76
The gelatin
shell.

The SGC
formed
outlet.

77
 The fill material of soft gelatin
capsules
1) liquids
a) water-immiscible volatile and nonvolatile liquids
b) water-miscible, nonvolatile liquids
c) water-miscible and relatively nonvolatile liquids
e.g. propylene glycol, isopropyl alcohol
d) Liquids that can easily migrate through the capsule
shell cannot be encapsulated into soft gelatin capsules
2) solids (solutions, suspensions, pasty mass, dry
powders, granules, pellets, or small tablets.)

78
Disadvantages of SGC
1. Special manufacturing equipment.
2. Limited choice of excipients.
3. Any change in water % affect hardness.
4. Hygroscopic & volatile compounds cause
hardening.
5. Acid & Alkalis cause hydrolysis & leakage.
6. Not for product Extract But,
Product Extract + carrier oil + beeswax + lecithin
=encapsulation)
7. Fish oil has bad odour & taste, thus includes
Conc. Of flavor.
79
 Comparison between HGC & SGC
HGC SGC

Shell prepared by Prepared in one step.

machine(company) and
filled by the other.
13-16% moisture. 30-40% during manufacture but
finally 7%.

Not used with water labile Used with water labile

substances. substances.
Bloom strength 200-250gm Bloom strength 150 gm.

Not with O2 sensitive API With O2 sensitive API

80
Compendial requirements for
capsules
1. Added subtances:Harmless-effective...
2. Containers:Tight,closed,light resistant.
3. Disintegrant test
4. Dissolution test.
5. Content uniformity( 9 of 10 85-115%,none out
of 75-125%)
6. Content labelling requirements.
7. Stability test.
8. Moisture permeation test.
9. Inspecting,counting,packaging&storing
capsules.
81
Compendial requirements for
capsules
Substances added to official preparations,
including capsules, to enhance their stability,
usefulness, or elegance, or to facilitate their
manufacture may be used only if they
1) are harmless in the quantities used
2) do not exceed the minimum amounts required to
provide their intended effect
3) do not impair the product’s bioavailability,
therapeutic efficacy or safety
4) do not interfere with requisite compendial assays
and tests
82
 The container and preservation
condition described in USP
containers
1) light resistant container:
2) well-closed container:
3) tight container:
4) Hermetic seal Container :
Preservation conditions
1) Freezer: -25 ~ -10 ℃; 2) Cold: <8 ℃; 3) Cool: 8 ~ 15 ℃;
4) Room Temperature: The temperature prevailing in a working
area.
5) Controlled Room Temperature: 20 ~ 25 ℃;
6) Warm: 30 ~ 40 ℃;
7) Excessive Heat: >40 ℃;
8) Protection from Freezing: (breakage of the container, loss of
strength or potency, destructive alteration of its
characteristics) 83
 Compendial requirements for
capsules
Disintegration test for capsules
The disintegration tests for hard and soft gelatin
capsules follows the same procedures and uses
the same apparatus as for uncoated tablets.
1) Method
The capsules are placed in the basket-rack assembly,
which is repeatedly immersed 30 times per minute into a
thermostatically controlled fluid at 37 ℃ and observed
over the time described in the individual monograph.
2) 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.
84
Compendial requirements for
capsules
Dissolution test for capsules
1) The apparatus, dissolution media and test is the
same as that for uncoated and plain coated tablets.
If the capsule shell interfere with the analysis, the
content of specified number of capsules can be
removed and the empty capsule shells dissolved in
the dissolution medium before proceeding with the
sampling and chemical analysis.
2) Generally, when a dissolution test is applied to an
existing capsule product, the disintegration test is
unnecessary.

85
 Compendial requirements for
capsules
Weight variation and content uniformity show the uniformity of dosage
units.
 Weight variation
Wcapsule – Wemptied shell = Wcontent 10 capsules
labeled amount or average amount, ±10%
1) For hard capsules
#1: Wcapsule should match Wemptied shell.
2) For soft capsules
#1: evaporating the washing solvent over 30 mins
#2: avoid uptake or loss of moisture
 Content uniformity
The amount of active ingredient should be within the range of 85% to
115% of the label amount for 9 of 10 capsules, with no unit outside
the range of 70% to 125% of label amount.
86
 Compendial requirements for
capsules
Other requirements:
1) content labeling: the quantity of each active
ingredient in each dosage unit.
2) stability testing
method: long-term stability testing, accelerated
stability test
aim: storage condition, shelf life
3) moisture permeation test: the USP requires
determination of the moisture permeation
characteristics of single- unit and unit dose-
containers to ensure their suitability for packaging
87
capsules.
Inspecting, counting, packaging,
and storing capsules
1) Inspecting
visual or electronic inspection → uniform
in appearance
2) Counting
a) counting tray;
b) counting and filling machines
3) Packaging
unit dose and strip packaging (sanitary,
identifiable, safe)
4) Storing
in tightly capped container in a cool, dry
place
88
 CAPSULE AUTO MATIC
POLISHING CAPSULE
MACHINE ARRANGEMNT
89
The Gel Mass (Capsule shell)

 The gel is prepared in a

300-litre stainless
steel vessel.

HOW?

90
 The Gel Mass (Capsule shell)
Gelatine powder
 mixed with water and glycerine that is then
 heated and stirred under vacuum.

The molten gelatin mass is then decanted into 200-

kg mobile vessels where colours and flavours can
be added using a turbine mixer that ensures
consistency of the gelatin mass.

 This mass is kept at a constant temperature until it

is needed for the next stage of the process
91
 The Medicine (Capsule fill)
 The medicine preparation area has a standard range
of mixers, homogenizers and milling equipment for
the preparation of the fills. The product being
prepared dictates what equipment has to be utilized.
 For simple oils the material is decanted into a 200
kg mobile vessel, positioned on a floor scale,
blanketed with Nitrogen, if required, and then sealed
ready for the next stage of the process.
 Blends of oils follow a similar process but a
Silverson mixer is used to ensure a uniform mix is
achieved.

92
 Encapsulation
 The gel and fill mobile vessels are then taken to the
encapsulation bays where each encapsulation machine
is segregated in individual bays.
 The molten gel is pumped to the machine and two thin
ribbons of gel are formed, one either side of the
machine.
 These ribbons then pass over a series of rollers and
over a set of dies that determine the size and shape of
the capsules.
 The fill is fed from its container to a positive
displacement pump, which accurately doses the fill and
injects it between the two gelatin ribbons prior to them
sealing together through the application of heat and
pressure.
 The resultant capsule is incredibly flexible due to the
water added to the gel mass and this excess has to be
removed
93
 Capsules fall from the machine and pass along a
conveyor into tumble dryers. These remove some
30% of the excess moisture, but the capsules are
still not dry enough for packing.
 Dry air is forced over the capsules to remove any
remaining free moisture from the capsules and
complete the drying process.
 Once dried, the capsules are removed from the
drying room to an inspection area. Here they
undergo visual inspection, which ensures the
quality of the product. The capsules are tipped
into intermediate containers and transferred to
the packing room. The capsules are
94
mechanically graded to ensure size uniformity.
Inspection

95
To Summarize!

96
97
98
 References
1. The theory and practice of industrial pharmacy.
Leon Lachman, Herbert A. Lieberman, Joseph L.
Kanig. Third edition. Varghese publishing house.
Page no. 681-703.
2. Pharmaceutical dosage forms: Tablets. Volume 3.
second edition. Leon Lachman, Herbert A.
Lieberman, Joseph B. Schwartz. Page no. 303-365.
3. Pharmaceutical process scale –up edited by Michael
Levin.
4. Modern pharmaceutics. Edited by Gilbert S.
Banker & Christopher T. Rhodes. 4th edition.
5. www.google.com 99
100