Capsules

Prepared by
Mrs. T. A. mandhare
Asst. prof. NIP, Nasrapur, Pune
1
Navsahyadri Pharmacy, Pune

 Introduction
 Definition
 Types of capsules-
 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.
 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
2Navsahyadri Pharmacy, Pune

 Capsule is derived from a Latin word
“capsula” means small container
 solid dosage forms in which drug is enclosed
within a hard or soft soluble shell.
 The casing of capsule is made up of gelatin.
 First capsule from gelatin was one piece
capsule by mothes and dublanc in France in
1834.
Navsahyadri Pharmacy, Pune 3

 Capsules are solid dosage form that contains
one or more medicinal or inert substances
contained in a shell most properly made of
gelatin.

 The drugs having unpleasant odour and taste can be
administered by enclosing them in a tasteless shell.
 They are smooth, become very slippery when moist and can
be easily swallowed.
 They are economical.
 They are easy to handle and carry.
 Capsules are made from gelatin and hence they are
therapeutically inert.
 They are attractive in appearance.
 Better bioavailability than tablets and faster onset of action
than tablets.
 The shells are physiologically inert and easily and quickly
digested in the gastrointestinal tract.
 The shells can be opacified (with titanium dioxide) or colored,
to give protection from light

 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.
 The concentrated preparations which need
previous dilution are unsuitable for capsules
because it may lead to irritation in stomach if
administered as such.

 There are two types :
Hard Gelatin capsules Soft Gelatin capsules
Eg. Omiprazol, Rabeprazol,
Amoxicillin, Ampicillin etc.
Eg. Folvite, calcitriol,
cutipreg, code liver
oil 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.

contain 12 - 16 % moisture
typically filled with dry solids
powders
granules
pellets
tablets
also contain colorant
preservatives
Cap
Body

SIZE VOLUME (cm3)
000 1.37
00 0.95
0 0.68
1 0.50
2 0.37
3 0.30
4 0.21
5 0.13

 1. The use of capsules avoid many unit operations that
associated with the manufacture of tablet.
 2. Beneficial for unpleasant taste and odour and attractive in
appearance.
 3. Easy to swallow with water.
 4. Possibility of filling different system; granules, pellets,
powders, tablets and liquid.
 5. The shells are physiologically inert and easily and quickly
digested in the GIT.
 6. Better bioavailability than tablets.
 7. They are economical.
 8. Easily to handle and carry.
 9. If used titanium dioxide or colour it provides protection from
light.
 10. Gives versatility to prepare any dose required for a variety of
administration routes.
 11. Alternation of drug release is possible.

 1. Easily tampered.
 2. Highly water soluble materials as iodides, bromides
and chloridesshould not be dispensed in capsules.
 3. Efflorescent materials softens the capsule and
deliquescent materials make it brittle due to effect of
humidity – stability problems.
 4. Homogeneity of fill weight.
 5. More expensive than tablets.

 Manufacture of HGC – Production of Gelatin
 • Why using gelatin?
 - The ability of a solution of a gel to solidify just above the
ambient temperature enabling the mold pin to solidify rapidly.
 - Nontoxic and used in food.
 - Readily soluble in biological fluid at body temperature.
 - Produce strong flexible film.
 - Homogeneous in structure giving good mechanical strength.
 - Make a sol at 50 ˚C.
 • Types of gelatin?
 - Type A : Produced by acid hydrolysis of bones, skin and
connective tissues of pork ( bovine).
 - Type B : Produced by alkaline hydrolysis of bone, skin and
connective tissues of animals.

 Bloom test:
 Bloom or gel strength the measure of the cohesive strength of cross
linking that occurs between gelatin molecules and it is proportional to the
molecular weight of gelatin.
 It is determined by measuring the weight in grams needed by specified
plastic plunger (0.5 inch diameter) to depress the surface of the gel at
specified temperature to a distance of 4 mm without breaking. The result
is expressed in bloom (grade) usually between 30 – 300. using 6.67%
gelatin solution kept for 17 hours at 10 ˚C prior to be tested.
 The higher the bloom value the higher the melting and gelling points and
the shorter the gelling time.
 Range of 150 – 280 is considered suitable for capsules manufacturing.

 • Viscosity :
 Determined on 6.67% concentration of gelatin in
water at 60 ˚C in a capillary pipette.
 Viscosity range 30 – 60 millipose is considered
suitable.
 As the viscosity lowered the capsule thickness
will decrease.
 • Microbiological tests:
 - Total microbial count
 a- total aerobic bacteria.
 b- molds
 c- preservative
 • generally used preservative are propyl paraben,
methyl paraben,sodium metabisulfite.

 Should exhibit water (moisture)content 12 – 15% w/w.
- Water act as plasticizer to ensure the mechanical properties of
capsule.
- If lower moisture content(<10%) , it will become brittle and
suffer dimensional changes may cause handling problems,
Moisture content(>16%), may cause problems in filling and
losses mechanical strength
- At excessive moisture levels, the capsule absorb moisture and
may soften and become tacky.
- Water soluble at 37 ˚C and insoluble below 30 ˚C and absorb
water.
 Should be stored in a sealed container at room temperature
at controlled humidity of 30% - 45%.

 Homogeneity: The particle size distribution of various
components should be similar to ensure homogeneous
mixing and to minimize segregation.
 The particle size distribution of the powder is preferable to
be monomodal of low polydispersity to ensure predictable
and reproducible flow during the filling process. Multimodal
and polydispersity of powder mix tend to segregate with
problems in homogeneity of the mix.
 Irregular particle shape e.g needle shape, will result in flow
problems and hence problems in the filling process and the
product.

 Angle of repose:
 - The angle that the powder makes with the horizontal plane.
 - If the angle of repose exceeds 50˚ the flow properties is
poor.
 - Angle of repose 25 ˚ is suitable.
 - Higher angle of repose requires the use of glidant.
 Torque rheometry:
 - stress is applied to the powder and the rate of shear is
determined to cause deformation. The powder of high
cohesion requires high shear strength to initiate and maintain
flow.
 Tap density: ----Hausner ratio
 - The density of the powder before shaking to the density
after shaking. 1.2 is acceptable but if exceed 1.6 it will be
unsuitable for capsule filling.

SOLID SEMISOLID LIQUIDS
Powders paste Oily liquids
Granules Thermo softening
Thyrotropic mixtures
Non-aqueous
solutions
Pellets
Tablets
Capsules

 Auger Fill principle:
 empty capsules – rectifying unit
 Rectifier descends the capsules such that caps are turned up and
bodies down.
 From rectifying unit these are placed one by one in filling ring
kept on rotating mode.
 The lower ring is rotated with a suitable speed and the hopper
containing powdered drug is held over this ring.
 The auger drives the drug into bodies.
 Vibratory Fill Principle:
 The feed is placed in the feed hopper and the capsule bodies are
passed under it.
 A perforated resin plate is placed in the feed hopper. Due the
vibrations of the resin plate, the powder flows freely through the
pores into bodies.
 - Osaka machines follows this principle.

 A- Dependent Method ( dosing system)
- bodies of capsules are separated and placed in the slots that are
located in the revolving turntable.
- Caps are housed above in the same turntable.
- The bodies is rotated under the hopper containing the powder.
- The powder falls into the capsules body cavities.
- The flow of the powder through the hopper and the homogeneity
of the powder are maintained by the circular movement of an
auger.
- then the caps and bodies brought together to form the finished
product.
- The weight of the powder is dependent on the length of time that
the hopper spends above the bodies which is dependent on the
speed of turntable.
- Capsules are then ejected out of machine.

 B- Independent Method ( dosing system)
- This method involves a physical transfer of a plug of powder
from the powder mix bed into the capsule body.
- A tube containing a spring-loading-piston, is depressed into
the powder bed enabling a pre-adjusted volume of powder
( plug) into the tube.
- The tube containing the powder is then elevated out of the
powder bed, rotated and located above the capsules body.
- The piston depressed and push the powder into the capsule
body.
- Then the caps and bodies came together and joined then
ejected.

 Various Filling Machine Available
 Eli-lily and Co
 Farmatic
 Hofliger and Karg
 Zanasi
 Parke-Davis.
These machine differ in their design and output

•Finished capsules from all filling equipment
require some sort of dusting or polishing
operation before the remaining operations.
• Following are the methods most commonly
used, based on desired output, formulation,
required final appearance, and so on.
 Pan polishing: Acela-cota pan is used to dust
and polish.
 Cloth dusting
 Brushing

 Sorting
•Unfilled capsules
• Filled unfitted capsule
• Loose caps
Commercial capsule sort/polish equipment are available-
Rotasort, Erweka KEA, PM60
 Sealing or locking
- Application of moisture and slipping
- Coloured band of gelatin
- Interlocking rings
- Heat spot welding by a heated needle

 Banding – Placing gelatin color bands at the meeting point of
caps and the bodies.
 Moistening – Moistening the inner surface of caps with
lukewarm gelatin solution.
 Spot Welding – Spot welding the joints which leaves a ring like
appearance at the point of sealing
Imprinting:
Imprinting is convenient method by which company and or
product identification information can be placed on each
capsule.

 Whether capsules are produced on a small scale or large scale
all of them are required to pass through certain tests i.e.,
quality control tests to test the quality of the finished product.
 The control procedures must ensure that finished, filled
capsules meet the appropriate current regulatory tests like
 Weight variation
 Content uniformity
 Disintegration test
 Dissolution test

 weigh 20 capsules individually and determine the avg weight
 The individual wts should be with in limit of 90-110% of avg wt
 If not all of capsules fall with in the limits, Weigh 20 capsules individually
 Remove the net content of each capsule with the aid of a small brush, these
are averaged
 Weigh the empty shells individually
 Determine the avg net content from the sum of individual net wt
 Then determine the difference b/w each individual net content and avg net
content
 LIMITS-
 Not more then 2 of the differences are greater then 10% of the avg net content
 No case is the difference greater then 25% wt range

 If more then 2 ,but not more then 6 capsules deviate from the
avg b/w 10-25%
 Determine the net contents of an additional 40 capsules
 Determine the avg content of entire 60 capsules
 Determine the 60 deviations from the new avg
 LIMITS-
 If the difference does not exceed 10% of the avg net content in
more than 6 of 60 capsules.
 No case does the difference exceed 25%
 Rotoweigh, Vericap 1200- capsule weighing machines
- operates at 73000 capsules per hour

 30 capsules are selected, of which 10 capsules are taken and
subjected to assay
 9 of 10 capsules should be in the range of +_15% (85-115%)
 And 10th capsule is not outside 75-125%.
 If more than 1, but less than 3, of the first 10 capsules fall
outside the85-115% limits, the remaining 20 are assayed.
 Limits:
 If all 30 capsules are within 75-125% of specified potency
range, and not less than 27 of the 30 are within 85-115%.

 The disintegration test determines the whether capsules disintegrated
with a prescribed time when placed in a liquid medium under the
prescribed integral conditions .
 METHOD-
 According to B.P and which applies to both hard and soft capsules
 1.introduce one capsule in each tube and suspend the apparatus in
 a beaker containing 60ml water at 370 C,
 – if hard capsules float on surface of water, the disc may be added.
 2.Operate the apparatus for 30 min, remove the assembly from the
liquid.
 3.the capsule pass the test if
 • No residue remains on the screen of the apparatus or,
 • If the residue remains, it consists of fragments shells ,
 • If a soft mass with no palpable core ,
 • If the disc is used any residue is remaining on its lower surface
should only consists of fragments of shells.

 The dissolution test is carried out using the dissolution
apparatus official in both the U.S.P and I.P.
 The capsule is placed in a basket , and the basket is
immersed in the dissolution medium and caused to rotate
at a specified speed.
 The dissolution medium is held in a covered 1000ml glass
vessel and maintained at 37 ℃ ±0.5 ℃ by means of a
constant temperature suitable water bath.
 The stirrer speed and type of dissolution medium are
specified in the individual monograph.

RESULT -
 Six capsules are tested and are accepted if each of them
is not less than monograph specified i.e., p +5%
 If it fails then additional six capsules are tested the result
is accepted if the avg. of 12 capsules is greater than or
equal to p and none of them is less than p-15%.
 If the capsule still fails the test the additional 12 capsules
are tested and are accepted if the avg. of 24 is greater
than to p, if not more than two less than p-15% and none
of them is less than p-25%

 HPMC Capsules
 QUALI-V, developed by Shionogi Qualicaps, is the first HPMC
capsule developed for eventual use in pharmaceutical
products
 Starch capsules
 Crosslinked Dextran capsules

Capsule shell manufacturing
 https://youtu.be/NVqN-Dinh48 -
 https://www.youtube.com/watch?v=FLXmiU
mcQog- manual capsule filling
 https://www.youtube.com/watch?v=AfDTMyF
eJZI- semiautomatic filling
 https://www.youtube.com/watch?v=6w72Fyr
CP7g- automatic capsule filling

 Soft gelatin capsules, also known as softgels or soft elastic capsules, are
hermetically sealed one-piece capsules containing a liquid, suspension or a
semisolid fill without a bubble of air or gas.
 Soft gelatin capsules are capsules in which the mechanical properties of
gelatin have been manipulated by addition of a plasticizer ( glycerol,
polyhydric alcohols as sorbitol) resulting in more flexible capsule.
 Soft gelatin capsules SGC may have a various shapes and sizes.

 The shape of soft gelatin capsule are round, oval,
oblong, tube.
 Maximum capsule size and shape convenient for
oral human use is:
 20 minim oblong
 16 minim oval
 9 minim round

1.Patient compliance: easy to sallow, no taste, tamper proof, unit dose
delivery.
2.Versatile: filled as semisolid, liquid, gel or paste. Various colors, shapes,
sizes.
3.Improved bioavailability: immediate or delayed by delivering drug in
solution.
4.Improve stability: drug is protected by lipophilic vehicle and capsule
shell.
5.Liquid flow in filling is more precise than powder flow. No dust.
Homogeneity.
6.Can be enteric coated for delayed release.
7.Popular for pharmaceutical and nutritional products.
8. Specialized dosage forms can be made
Eg. Chewable, extended release, opthalmic preparations, vaginal or rectal
suppositories.

• Requires special manufacturing equipment.
• Stability issues for water soluble drugs.
•Possibility of interactions between liquid and gelatin shell.
• Limited choices for excipients.
• Highly moisture sensitive efflorescent material can not be
incorporated, they may cause softening or leaching.
• Deliquescent material can not be incorporated, they may cause
hardening or brittle capsules.

•Gelatin type B – alkali processed, constitutes 40% of melt gel.
• Plasticizer
• Water
•Other additives which may be added as colorants,
opacifier, preservativ, flavouring agents,sugars. acids and medicaments
to achieve desired effects.
• IMPORTANT SPECIFICATIONS OF GELATIN-
Blooms strength:150-250gm,viscosity, iron content

•Incorporated to provide flexibility and elasticity to the shell.
• 20 -30 % of the wet gel formulation.
•The compatibility with the fill formulation determine the plasticizer.
•The mechanical properties of the capsule determine the concentration.
• Above 30% result in too flexible capsules and below 20% will result in too brittle capsules.
•Glycerol, Sorbitol, propylene glycol or mixtures are frequently used.
 PLASTICIZER AND GELATIN RATIO
 The plasticizers used with gelatin in soft capsule
 manufacture are relatively few. Glycerin USP, Sorbitol USP, Pharmaceutical Grade Sorbitol Special,
and combinations of these are the most prevalent. The ratio by weight of dry plasticizer to dry gelatin
determines the "hardness" of the gelatin shell, In soft gelatin capsule the amount of plasticizers
(glycerin) 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

•Water accounts for 30 – 40% of the wet gel to facilitate proper
processing during gel preparation.
•Excess water is removed by controlled drying.
•Water content in the finished capsule should be 5 – 8%, to keep
the physical stability .
•Improper storage conditions may make the capsules too soft or
too hard and embrittled.

• Colors-colour used in shell has to be darker than encapsulating material, may be
natural or synthetic.
• Insoluble pigments, soluble pigments with or without opacifier can be used.
• Opacifier- Titanium dioxide is generally used for suspension or to guard against
light.
• Preservative- Methy paraben, propyl paraben, sodium sulfite may be used as
preservative.
• Chelating agents-iron is always present in raw gelatin & should not be more than
15 ppm.
• Chelating agents may be added to prevent the reaction of iron with material or
colour.

 A) Bloom or gel strength: It is a measure of
cohesive strength of cross-linkage that occurs
between molecules and is proportional to the
molecular weight of gelatin.
 Bloom is determined by measuring the weight in
grams required to move a plastic plunger of 0.5
inches in diameter, 4mm to depress the surface
of 6.67 % gelatin gel that has held at 10°C for
17-18hrs without breaking.
 The unit of bloom is grams and it is between
150-250g.

 In general, with all other factors being equal, the higher the
Bloom strength of the gelatin used, the more physically stable
is the resulting capsule shell.
 The cost of gelatin is directly proportional to its Bloom or gel
strength and thus is an important factor in the cost of soft
capsules.
 Consequently, the higher Bloom gelatins are only used when
necessary to improve the physical stability of a product or for
large capsules (over 50 minims), which require greater
structural strength during manufacture.

 B) Viscosity: Is determined on a 6.67%
concentration of gelatin in water at 60°C , is a
measure of the molecular chain length and
determines the manufacturing characteristics of
the gelatin film.
 Low viscosity (25-32 millipoise) with high Bloom (180-
250g) gelatin used for capsulation of hygroscopic vehicles
or solids and standard gelatin formulas can be
modified so as to require up to 50% less water for
satisfactory operation on the capsulation
machine.
 These modified formulas afford less opportunity
for the hygroscopic fill materials to attract water
from the shell and thereby improve the ingredient
and physical stability of the product Navsahyadri Pharmacy, Pune 68

 C) Iron content:
 Is always present in the raw gelatin,
and its concentration usually depends
on the iron content of the large
quantities of water used in its
manufacture.
 Gelatins used in the manufacture of
soft gelatin capsules should not
contain more than I5 ppm of this
element, because of its effect on
Food, Drug, and Cosmetic (FD&C)
certified dyes and its possible color
reactions with organic compounds.

•The liquid-phase fill matrix is selected according to the following
criteria:
1. Capacity to dissolve the drug.
2. Rate of dispersion in the GIT after softgel shell rupture.
3. Capacity to retain the drug in solution in the GIT fluid.
4. Compatibility with the gelatin shell.
5. Ability to optimize the rate, extend and consistency of drug
absorption.

❖ The content of soft gelatin capsule is a liquid, or a combination of miscible
liquids, a solution of solid in a liquid or suspension of solid in liquid.
❖ Liquids are both water-miscible and volatile can not be included as a major
constituent of capsule content since Liquids they can migrate into the hydrophilic
gelatin shell and volatilize from its surface. Water, ethyl alcohol, and, of course,
emulsions fall into this category.
❖ Gelatin plasticizers such as glycerin and propylene glycol can not be major
constituents of the capsule content, owing to their softening effect on the gelatin
shell, which thereby makes the capsule more susceptible to effects of heat and
humidity.

 As a minor constituents (up to 5% of cap. contents) water and alcohol can be
used as cosolvent.
 Up to 10% glycerin/ PG can be used as cosolvent.
 Also, preparations for encapsulation should have a pH between 2.5 and 7.5,
since preparations that are more acidic can cause hydrolysis and leakage of the
gelatin shell. And preparations that are more alkaline can tan the gelatin and
thus affect solubility of the shell.
 The capsulation of water immiscible liquids (vegetable oils and mineral oils)
is the simplest form of soft gelatin capsulation and usually requires little or no
formulation.
➢ All liquids, solutions, and suspensions for capsulation should be homogeneous
and air-free and preferably should flow by gravity at room temperature, since
the sealing temperature of the gelatin films is usually may range of 37 to 40 ͦC.

 Except for Accogel process (which is primarily concerned with the
capsulation of dry powders) , solids are filled into soft capsules in the form of
either solution or suspension.
 The preparation of a solution of a solid medicament should be the first goal;
usually the solution is easily capsulated and exhibit better uniformity, stability
and biopharmaceutical properties than suspension.
 For oral products, the medicament should have sufficient solubility in the
solvent system so that the necessary dose is contained in a maximum fill volume
of 16 to 20 minims (1 to 1.25 ml).
 Solids are not soluble in the solvent system are capsulated as suspension.
 The choice of suspension medium are directed toward producing the smallest
size capsule .
 In the formulation of suspensions for soft gelatin encapsulation, certain basic
information must be developed to determine the minimum capsule size.
 Laboratory tool for this purpose is: BASE ADSORPTION

 Base adsorption (of solids to be suspended): is expressed as number of
grams of liquid base (insert liquid or vehicle) or minimum quantity of base
required to produce a capsulatable mixture when mixed with one gram of
solid(s).
➢ The base adsorption of solid is influenced by :
❖ The solid particle size and shape
❖ Its physical state ( fibrous, amorphous or crystalline)
❖ Its density, moisture content, oleophilic or hydrophilic nature.
 In the determination of base adsorption, the solid(s) must be completely wetted
by the liquid base. For glycol and nonionic type base, the addition of a wetting
agent is seldom required, but for vegetable bases, complete wetting of the solid s
is not achieved without an additive. Soy lecithin, at a concentration 2to3% by
weight of the oil, serves excellent for this purpose

 The base adsorption is used to determine the “
minim per gram “ factor (M/g) of the solids .
 The minim per gram factor is (the volume in minims
that is occupied by one gram of the solid plus the
weight of liquid base(BA) required to make a
capsulatable mixture).
 Or volume of mixture in minim required for solid drug
to produce a mixture which can be capsulated.
 Example of liquid base is vegtable oil, PEG 400,
Polysorbate 80, Glyceryl monooleate.

 The minim per gram factor is calculated by dividing the
weight of base plus the gram of solid(BA+S) by the weight of
mixture(W) per cubic centimeter or 16.23 minims (V).
 The lower the base adsorption of the solid and the higher
the density of the mixture, the smaller the capsule will be.

 You are going to prepare SGC (2 gram mixture)of drug X (1gm)
by using vegetable oil (liquid base)BA (0.75 gm) and Mg value is
25 then the SGC volume will be
(0.75+1)*v
25= ---------------------------
2
V= 28.57 minims
16.23 minims=1ml
So 28.57 = 1.57 ml
 So SGC of drug X will have capsule content of about 1.57 ml

 Is manufactured by following methods:
 Plate process
 Rotary die process
 Reciprocating die (developed process for rotary
die)
 Accogel machine (unique equipment that
accurately fills powdered dry solids into S.G.C.)
 Seamless process (Bubble Method)

 Gelatin sheet is placed 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.

 The material to be encapsulated flows by gravity.
Two plasticized gelatin ribbons are continuously and
simultaneously fed with the liquid or paste fill
between the rollers of the rotary die mechanism
where the capsule are simultaneously filled, shaped,
hermetically sealed and cut from the gelatin ribbon.
 The sealing of the capsule is achieved by mechanical
pressure on the die rolls and the heating(37-40°C) of
the ribbons by the wedge.

•The two roller dies have cavities.
• Gelatin ribbons come from two sides made by means of the cooling drum.
• The fill come from the pump above the rollers.
• The injection wedge inject the required amount of fill when the cavities of
the two die rolls come together.
• By means of pressure and controlled temperature ( 37 -40 ˚C ) the two sides
of ribbons welded together forming the capsule in the shape of die
cavities.
• By means of conveyor the capsules transferred to the drying chamber.
• Drying conditions is 20 – 30% RH at 21 – 24 ˚C.

 Reciprocating die Process - (Norton Capsule Machine)
 This continuous soft gelatin capsule processing technology
was developed by Norton Company in 1949.
 This process is similar to rotary process in that ribbons of
gelatin are formed and used to encapsulate the fill, but it
differs in the actual encapsulating process.
 The gelatin ribbons are fed between a set of vertical dies that
continually open and close to form rows of pockets in the
gelatin ribbons. These pockets are filled with the medication
and are sealed, shaped, and cut out of the film as they progress
through the machinery. As the capsules are cut from the
ribbons, they fall into a cooled solvent bath that prevents the
capsules from adhering to one another.
Reciprocating die Process

 Although the rotary die process and reciprocating die process
were capable of producing soft gelatin capsules containing oily
liquids and pastes, Lederle Laboratories in 1949 developed
accogel process, a continuous process that produces soft gelatin
capsules containing powders and granules.
 The process involves a measuring roll that holds the fill
formulation in its cavities under the vacuum and rotates directly
above the elasticized sheet of the gelatin ribbon. The ribbon is
drawn into the capsule cavities of the capsule die roll by vacuum.
The measuring rolls empty the fill material into the capsule-
shaped gelatin cavities on the die roll. The die roll then
 converges with the rotating sealing roll covered with another
sheet of elasticized gelatin. The convergence of two rotary rolls
creates pressure to seal and cut the formed capsules

 The seamless technique produces one-piece soft gelatin
capsules without the use of dies. The process is often
referred to as a bubble method that creates seamless,
spherical soft gelatin capsules called pearl.
 In this process, a molten gelatin stream ﬂows though the
outer nozzle of a concentric tube at a constant rate, and the
medicated liquid formulation is dispensed through the inner
orifice by means of a precision metering pump. The
emerging stream is broken up into an intermittent but steady
ﬂow of uniform-sized by a pulsating mechanism, leading to
the formation of droplets enveloped in molten gelatin. The
formed capsules are quickly removed from the nozzle,
slowly congealed, and automatically ejected from the
system.

-Visual inspection
- Appearance : shape, colour, size ,
-thickness of the shell-measured under microscope
- Moisture content test – toluene distillation method
• Weight variation
• Disintegration test.
• Dissolution test.
• Content uniformity test
 Finally physical control processing and packing may be accomplished by the
following in line continuous operations
 1.A capsule diameter sorter allows to pass to the next unit of any capsule with in ±
0.020 inch of theoretical diameter of the particular capsule being tested. overfills,
underfills, and “foreign” capsules are discarded.
 2.A capsule colour -the capsules are fed to it automatic from the diameter sorter by
a pneumatic conveyer. In this unit, any capsule whose colour does not conform to
the reference colour standard for that particular product is discarded others passes
the test.

 Unprotected soft gelatin capsules rapidly reach
equilibrium with the atmospheric conditions under
which they are stored.
 This inherent characteristic warrants a brief discussion
of the effects of temp and humidity on the products.
 General statements relative to the effects of temp and
humidity on soft gelatin capsules must be confined to a
control capsule that contains mineral oil with a gelatin
shell having a dry glycerin to dry gelatin ratio of 0.5-1
and water to dry gelatin ratio of 1-1 and which is dried
to equilibrium with 20-30% RH and 21-24℃.

 The physical stability of soft gelatin capsules is associated
primarily with the pick up or loss of water by the capsule
shell .
 If these are prevented by proper packaging ,the above
controlled capsule should have satisfactory physical
stability at temp ranging from just above freezing to as high
as 60℃
 As the humidity increases the moisture content pickup of
capsules increases .
 ex- at 30%RH at room temp shows that gelatin retain about
12%(48 mg) of water and glycerin 7%(14 mg)of water.
 at 60%RH the moisture content should be 17.4%. High
humidity (>60%RH at 21-24℃ )produce more lasting
effects on the capsule shell.

 Since as moisture is absorbed ,the capsules become
softer, tackier, and bloated.
 The capsule manufacturer routinely conducts accelerated
stability tests on new product as an integral part of the
production development program.
 The successful results are obtained by conducing at test
conditions like
 1.80%RH at room temp in an open container
 2.40 ℃ in open container
 3.40 ℃ in closed container (glass bottle with tight screw
cap)

 chemists conducting the physical stability test in their own lab
should keep two important points in mind
 1. Prior to testing ,the capsule should be equilibrated to known
atm conditions, preferably 20-30%RH at 21-24 ℃.
 2. Evaluation of the results of the previously described heat
test should be made only after the capsules have returned to
equilibrium to room temp

 Allen L. and Ansel H. (2014). Ansel’s Pharmaceutical
Dosage Forms and Drug Delivery Systems.
Philadelphia: Lipincott Williams and Wilkins.
 Aulton, M. and Taylor, K. (2013). Aulton’s
Pharmaceutics: The Design and Manufacture of
Medicines, (4th ed.). Edinburgh: Churchill Livingstone.
 Lachman/Lieberman’s, The Theory and practice of
Industrial Pharmacy, (4th ed.).

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