Hard gelatin capsules are solid dosage forms where medicinal agents are enclosed within a gelatin shell. The shell consists of two cylindrical sections (cap and body) that fit together. Empty shells are supplied to be filled later. During filling, the body is filled with drug and then closed with the cap. Soft gelatin capsules contain liquid or semi-solid fills and have a seam where the two gelatin halves are joined. They are manufactured through plate coating, rotary die, or globex processes. Filling machines orient, open, fill, seal, and eject capsules in an automated process.

1. Non-Sterile
Manufaturing of
CAPSULES
Prepared by: Dr. Kandekar Ujjwala Y.
JSPM’s Rajarshree Shahu College of Pharmacy and
Research, Tathwade, Pune

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 Hard gelatin capsules also known as hard-shell gelatin capsules or two-piece
capsules are solid dosage forms in which one or more medicinal agents and/or inert
materials are enclosed within a small shell.
 A hard gelatin capsule shell consists of two prefabricated, cylindrical sections (a cap
and a body) each of which has one rounded, closed-end and one open end. The body
has a slightly lower diameter than the cap and fits inside the cap.
 Hard gelatin capsule shells are fabricated and supplied empty to the pharmaceutical
industry by shell suppliers and are then filled in a separate operation. During the
capsule filling unit operation, the body is filled with the drug substances and the
shell is closed by bringing the body and the cap together.

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Components of hard gelatin capsules
Hard gelatin capsule shell is composed largely of gelatin. Other than gelatin, it may
contain:
• Plasticizer
• Colorants
• Opacifying agents
• Preservatives
These enable capsule formation or improve their performance.
• Hard gelatin capsules also contain 12–16% water, but the water content can vary,
depending on the storage conditions.

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Capsule sizes and shapes
Empty hard gelatin capsule shells come in a variety of sizes ranging from an arbitrary
numbering of 000 to 5 with 000 being the largest size and 5 being the smallest.
The size of hard gelatin capsule selected for use is determined by requirements of the
formulation, including the dose of the active ingredient and the density and
compaction characteristics of the drug and other components.
The first step to estimating the optimal capsule size for a given product is to
determine the density of the formulation using tapped density for powders and bulk
density for pellets, minitablets, and granules.
The appropriate capsule size may then be calculated using the measured density of
the formulation, the target fill weight, and capsule volume.
The fill weight for liquids is calculated by multiplying the specific gravity of the liquid
by the capsule body volume multiplied by 0.9.
To accommodate special needs, some intermediate sizes (‘elongated sizes’) are
produced. These capsule sizes typically have an extra 10% of fill volume compared to
the standard sizes e.g. elongated size 00 capsules (00el), elongated size 0 capsules
(0el) etc.

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Manufacture of empty hard gelatin capsules
Hard gelatin capsules are manufactured using a dip-coating method and the various
stages involved are as follows:
Step 1: Preparation of the gelatin solution (dipping solution)
Step 2: Dip-coating the gelatin solution on to metal pins (moulds)
Step 3: Rotation of the Dip-coated pins
Step 4: Drying of the gelatin-coated pins
Step 5: Stripping and trimming
Step 6: Joining of the trimmed capsule shell
Step 7: Printing

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Step 1: Preparation of the gelatin solution (dipping solution):
A concentrated solution of gelatin is prepared by dissolving the gelatin in demineralized
water which has been heated to 60–70°C in jacketed pressure vessels.
This solution contains 30 – 40% w/w of gelatin and is highly viscous, which causes bubbles
as a result of air entrapment. The presence of these bubbles in the final solution would yield
capsules of inconsistent weight and would also become problematic during capsule filling
and upon storage. To remove the air bubbles, a vacuum is applied to the solution.
colourants and pigments are added to attain the desired final capsule appearance. At this
stage, other processing aids may be added, such as sodium lauryl sulfate, to reduce surface
tension. The solution viscosity is measured and adjusted as needed with hot demineralized
water to achieve the target specification.
After physical, chemical, and microbiological testing, the gelatin is released for capsule
production.

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Step 2: Dip-coating the gelatin solution on to metal pins (moulds)
Capsule shells are manufactured under strict climatic conditions by dipping pairs
(body and cap) of standardized steel pins arranged in rows on metal bars into an
aqueous gelatin solution (25 – 30% w/w) maintained at about 50 ° C in a jacketed
heating pan. Because the moulds are below the gelling temperature, the gelatin begins
to form a thin gelatin layer or film on the moulds.
The rows of pins are arranged so that caps are formed on one side of the machine
while bodies are simultaneously formed on the opposite side of the machine.

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Step 3: Rotation of the dip-coated pins
The bar containing the pins is removed and rotated several times to evenly distribute
the solution around the pins, correct gelatin distribution being critical to uniform and
precise capsule wall thickness and dome strength.
Step 4: Drying of the gelatin-coated pins
Once the gelatin is evenly distributed on the mould, a blast of cool air is used to set the
gelatin on the mould. At this point, the gelatin is dried, and the pins are then passed
through several drying stages to achieve the target moisture content.
Step 5: Stripping and trimming
After the gelatin is dried, the capsule is stripped off the mould and trimmed to the
proper length.

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Step 6: Joining of the trimmed capsule shell
Once trimmed, the two halves (the cap and body) are joined to the pre-closed position
using a pre lock mechanism. At this point, printing is done if needed before packing in
cartons for shipping.
Step 7: Printing
After formation, the capsule shells can be printed to improve identification. Printing
can be achieved using one or two colours, containing information such as product
name or code number, manufacturer’s name or logo and dosage details.

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Filling of hard gelatin capsules
o The filling of hard gelatin capsules is an established technology, with equipment available
ranging from that for very small-scale manual filling (e.g., Feton capsule filling machine),
through intermediate-scale semi-automatic filling to large-scale fully automatic filling. Hard
gelatin capsules can also be hand-filled one at a time, as done in a compounding pharmacy.
o The basic steps in filling hard gelatin capsules include:
o Rectification of capsules (placing empty gelatin capsules on the removable plate with bodies
facing downward).
o Separation of caps from bodies.
o Dosing of fill material (The body is filled with the formulation manually using a plastic spatula,
and the excess powder is removed).
o Replacement of caps/ closing capsule shells
o Ejection of filled capsules

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Hand operated hard gelatin capsule filling machines:
The empty capsules are filled into the loading tray which is then placed over the bed. By
opening the handle, the bodies of the capsules are locked and caps separated in the loading
tray itself which is then removed by operating the lever.
The weighed amount of the drug to be filled in the capsules is placed in powder tray already
kept in position over the bed. Spread the powder with the help of a powder spreader so as to
fill the bodies of the capsules uniformly.
Collect excess of the powder on the platform of the powder tray.
Lower the pin plate and move it downward so as to press the powder in the bodies.
Remove the powder tray and place the caps holding tray in position. Press the caps with the
help of plate with rubber top and operate the lever to unlock the cap and body of the capsules.
Remove the loading tray and collect the filled capsules in a tray.

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Process of filling capsules involves:
o Rectification where the machine automatically orients the capsules
o Opening the capsules
o Filling capsules
o Sealing/covering capsules
o Ejecting fully-filled capsules

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Auger Filling Machine:
Powder or granules are contained in mass
flow hoppers with rotating augers • Powder
is fed continuously out of the hopper outlet
due to the rotation of the auger. • Amount of
powder fed into the body depends on the
time capsule body spends underneath the
hopper outlet and auger speed - slower
rotation increases the fill weight.

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Vibratory fill principle:
In the powder, a perforated resin plate is positioned and connected to a vibrator.
• The powder blend tends to be fluidized by the vibration of plate and assists the
powder to flow into the bodies through the holes in resin plate.

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The Working Principle of Tamping Pin (Dosing Disc)
Dosing disc
 Dosing disc rotates continuously in a circular manner depending on the preset speed.
 tamping plate (“stop” plate) closes the holes on the dosing plate.
 As the dosing disc rotates below the powder bed, the filler material flows into each hole. The
pins, which are in the tamping stations compress the powder to a controlled depth.
 As the filler material flows into the first hole in the disc, tamping pin 1 compresses it to a
predetermined depth.
 After this first step, the hole moves to the next stage where the powder again flows into the hole
and tamping pin 2 compresses it to a predetermined depth.

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DOSING DISC PRINCIPLE:
A solid ‘stop’ brass plate is sliding down the dosing disc to close off the hole.
Five sets of pistons compress the powder into cavities to form plugs
DOSATOR PRINCIPLE:
 It consists of cylindrical dosing tube fitted with movable piston.
 The position of the piston is preset to a particular height to define a volume.
 Powder enters the open end of dosator and is slightly compressed against the
piston into a plug

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Stage 1
Force the dosator into the powder bed. This forces the powder to fill the cavity at the tip of dosator.
Normally the size of the cavity will depend on the level of the dosator plunger (section in color red). Remember,
the arrows indicate how the dosator components move.
Stage 2
The powder fills the cavity and the plunger compacts it within the dosator. This locks the powder in the dosator
cavity.
Stage 3
The dosator retracts from the powder bed carrying with it the powder in the cavity.
Stage 4
At this point, the tip of the filled dosator should be free from excess powder. A process referred to as “doctoring”.
That is, cutting off the excess powder that hangs at the tip of dosator.
Stage 5
Dosator can now eject the powder in the capsules.

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CAPSULE SEALING
1. sealing the joint between the 2 capsule parts
2. Sealing them with colored band of gelatin (Kapseals).
3. Through a heat welding process that fuses the capsule cap to the body through the
double wall
thickness at their juncture - distinctive ring around the capsule where heat welded
Example: Weld’s gelatin seal
Liquid wetting agent that lowers the melting point in the contact areas of the
capsule’s cap and the body using low temperatures (40-450C)
5. Lightly coating the inner surface of the cap with a warm gelatin solution
immediately prior to placement on the filled capsule body.

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CAPSULE FILLING MACHINES
• Eli Lilly and company, Indianapolis, IN
• Farmatic SNC, Bologna, Italy
• Hofliger and Karg, Waiblingen, Germany
• Macofar SAS, Bologna, Italy
• mG2 S.p.A., Bologna, Italy
• Osaka, Osaka, Japan
• Parke-Davis and company, detroit, MI
• Perry Industries, Green Bay,WI
• Zanasi Nigris,S.p.A., Bologna, Italy

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Difficulties in filling capsules
1. Deliquescent or Hygroscopic powders – a gelatin capsule contain 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 an adsorbent like magnesium carbonate, heavy magnesium oxide or light
magnesium oxide overcomes this difficulty provided the capsules are packed in tightly closed glass
capsule vials.
2. Eutectic mixtures – certain substances when mixed together tend to liquefy and form a pasty mass
due to the formation of a mixture which has a lower melting point than room temperature. For filling
these types of substances each troublesome ingredient is mixed with an absorbent separately then
mixed together and filled in capsules.
The absorbents used are magnesium oxide and kaolin.
Another method in dealing with such type of difficulty is that the substances are mixed together so
as to form a eutectic mixture, then an absorbent like magnesium carbonate or kaolin is added.

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3. Use of two capsules –
some of the manufacturers 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.
4. Filling of granular powder – some powders which lack adhesiveness and most
granular powders are difficult to fill in the capsules by punch method because they are
not compressible and flow out of the capsule as soon as they are lifted from the pile of
powder into which they are punched.
To overcome this difficulty the non-adhesive powders should be moistened with
alcohol and the granular powders should be reduced to powder before filling into
capsules.

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SOFT GELATIN CAPSULES
Also referred to as as Soft Elastic Capsule.
Are prepared from shells of gelatin plasticized by the addition of glycerin,
sorbitol or polyol.
The shell may contain preservatives to prevent from fungi.
A soft gelatin capsule has a seam at the point of closure of the 2 halves, and the
contents can be liquid, paste or powder.

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Methods For commercial Manufacture of Soft
Gelatin Capsule
1. Plate-Process.
A warm sheet of prepared gelatin is laid over the lower plate and the liquid is poured on it.
A second sheet of gelatin is carefully put in place and this is followed by the top plate of the
mould.
The set is placed under the press where pressure is applied to form the capsule which are
washed off
with a volatile solvent to remove any trace of oil from exterior.

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Rotary Die Method
Liquid gelatin flowing from an overhead tank is formed into two
continuous ribbons by the rotary die machine and brought together
between twin rotating dies.
At the same time, metered fill material is injected between the ribbons
precisely at the moment that the dies form pockets of the gelatin ribbons.
These pockets of fill-containing gelatin are sealed by pressure and heat
and then severed from the ribbon.
The capsule is washed with organic solvent and pre-dried.
Advantages:
- capsules can have all kinds of shapes and sizes
- different colors for both sides
wide variety of fills
• Disadvantages:
- high amount of shell waste material
- longer drying time compared to Globex Method

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Globex Method
• Filling is pumped through the inner capillary of a concentric double
capillary
• Shell forming solution is pumped through the outer capillary of the
concentric double capillary
• The soft capsules are then immersed in a cooling bath of about 4oc
(usually liquid paraffin).
• Cooling bath ensures immediate sol-gel transformation, hence
formation of flexible yet firm robust outer film.
Soft capsules are collected, washed with organic solvent to remove
residues of cooling liquid, and gently dried at a relative humidity of
20% in infrared tunnels.
• Advantage:
production of seamless capsules which are tamper-evident and free of
contamination or entrapped air.

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Reference
1. Allen L. V and Ansel H. C. (2014). Ansel’s Pharmaceutical Dosage Forms and Drug
Delivery Systems. Philadelphia: Lippincott Williams and Wilkins.
2. Kottke, M. and Rudnic, E. (2002). Tablet Dosage Forms. In G. Banker and C. Rhodes
(Eds), Modern Pharmaceutics (pp. 437-511). New York: Marcel Dekker, Inc.
3. Lachman, L., Lieberman, H. A., and Kanig, J. L. (1986 ), The Theory and Practice of
Industrial Pharmacy, 3rd ed. , Philadelphia: Lea & Febiger.
4. Sakr, A. A and Alanazi, F. K (2012). Oral Solid Dosage Form. In L.A Felton
(Eds.), Remington Essentials of Pharmaceutics (pp. 581-610). London:
Pharmaceutical Press.
5. Aulton, M. and Taylor, K. (2013). Aulton’s Pharmaceutics: The Design and
Manufacture of Medicines, (4th ed.). Edinburgh: Churchill Livingstone.

37. Thank You
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