26-08-2021

HARD GELATIN CAPSULE

FORMULATION & MANUFACTURING

Dr. GSN Koteswara Rao (Eswar)

M.Pharm, PhD, MBA
Vice Principal and Professor
K L College of Pharmacy
K L University

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TYPES OF CAPSULES
 Hard capsules;
 Soft capsules (softgels);
 Modified-release capsules:
 Delayed-release capsules (gastroresistant / enteric
capsules)
 Sustained-release capsules (extended /prolonged
release capsules).
 Special capsules

Type of capsules depend on plasticizer content ,

technological principle and special feature

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Dr. GSN Koteswara Rao, KLU 1

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STAGES OF CAPSULES PRODUCTION

HARD GELATIN CAPSULES SOFT GELATIN CAPSULES
PREPARATION PREPARATION
1. Preparing of gelatin 1. Preparing of gelatin
solution. solution.
2. Preparing of gelatin 2. Preparing and
shells. filling of soft-gelatin
3. Hard-gelatin capsules.
capsule filling.
4. Packing and 3. Packing and
labeling. labeling.

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Types of maTerials for filling inTo HgC

Dry solids
• Powders
• Pellets
• Granules
• Tablets
Semi solids
• Thermo softening mixtures
• Thixotropic mixtures
• Pastes
Liquids
• Non aqueous liquids
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Diluents:
 To improve bulk & to provide cohesiveness which is essential
demanded by some capsule filling machines.
 Hydrophilic diluents are responsible for capsules formulated
with hydrophobic drugs.
 Moisture content of diluents may influence cohesiveness,
fluidity, lubricity & dissolution rate of drug.
 Amount of diluents required is determined based on amount
of API, proportion of other components & selected capsule
size.

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 Bentonite, Calcium Carbonate, Mannitol, Magnesium

Carbonate, Magnesium Oxide.

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Disintegrants:
 Used to rupture plugs, compacts present in capsule & to
distribute capsule contents in stomach.
 Eg:- Pre gelatinized starch, cross carmellose, sodium starch
glycolate.
Surfactants:
 To overcome wetting problem of hydrophobic drug in
biological fluids, surfactants (SLS & sodium docusate) at 0.1-
0.5% levels are used.
 Used to minimize water proof effect of hydrophobic
lubricants.

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Water:
 To prepare dipping solution, hot demineralized water is used
& portion of water is retained as residual moisture content in
finished capsule.
 Amount of water retained is influenced by composition of
shell & conditions employed during processing & storage.

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Plasticizers:
 To reduce brittleness of shell & to provide flexibility to film.
 Glycerol, sorbitol, propylene glycol, sucrose, acacia

 Usually employed at 20 – 40%

 To enhance effect of plasticizer (2 – 6%)

 Glycine, mannitol, acetamide, formamide, lactamide.

 Gelatin capsules produced with 5% PEG 4000 showed

improved physical characteristics over standard capsules &
they are relatively less brittle.

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Preservatives:
 Natural component gelatin & water may encourage growth of
microbial organisms.

 Demand for preservative is very less as entire procedure is

controlled by a process adhered to GMP requirements.

 Eg:- Parabens

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Lubricants/ glidants:
 For improvement of flow characteristics.

 Applied to pins prior to its immersion in dipping solution.

 It facilitates ease of removal of finished capsule from pins, to

reduce tendency of adhering to pins & to prevent formation of
defect capsules.
 Concentration :- 2 % or less.

 Eg:- Mineral oils, Magnesium stearate, glycol esters,

silicones.

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Colorants & opaquing agents:

 Opacifiers (titanium dioxide)  employed to provide slight
stability to contents & to reduce concentration of colourants.
 Used to achieve good elegance, to identify capsule & to
improve patient compliance.
 Capsule colour may be selected based on disease to be cured
with that capsules .
 Water soluble dyes & water insoluble pigments can be used
to impart required intensity of colour to capsule.

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Dr. GSN Koteswara Rao, KLU 6

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Colorants

Water
soluble Pigments
dyes

Titanium
Synthetic Natural Iron oxides
dioxide

azo Non-azo Black Red

Quinoline
erythrosine Yellow
yello

Indigo
carmine

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 Hard capsules have shells consisting of two

prefabricated cylindrical sections that fit together.
 One end of each section is rounded and closed, and
the other is open. The contents of hard capsules are
usually in solid form (powder or pills or granules).

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INDUSTRIAL-SCALE FILLING
 The machines for the industrial-scale filling of
hard gelatin capsules come in great variety of
shapes and sizes.
 Various types of filling techniques are:
 Extemporaneous filling
 Manual filling
 Semi-automatic filling
 Automatic filling
 Auger filling
 Direct dosing
 By dosator
 By dosing disc and tamping finger

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EXTEMPORANEOUS FILLING
 It is in-situ filling of capsules and not in use,
now-a-days.

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HAND FILLING
 Hand-operated capsule filling machine or Feton capsule
filling machine
 Consist of a couple of plates and are capable of
producing about 200 to 2000 capsules/hr.

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A hand operated gelatin capsule

filling machine consists of the
following parts:

1. A bed with 200-300 holes

2. A capsule loading tray
3. A powder filling tray
4. A pin plate having 200 or 300
pins corresponding to the
number of holes in the bed and
cap holding tray.
5. A lever handle
6. A Cam handle
7. A plate fitted with rubber top

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https://youtu.be/FLXmiUmcQog

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Dr. GSN Koteswara Rao, KLU 10

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SEMI-AUTOMATIC FILLING
The process of working includes:

 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 8 hour
shift

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RECTIFICATION
 The empty capsules are oriented so that all point
the same direction i.e. body end downwards

 In general, capsule pass one at a time through a

channel just wide enough to provide grip at cap
end

 The capsules will always be aligned body end

downwards, regardless of which end entered the
channel first with the help of specially designated
blades

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SEPARATION OF CAPS FROM BODY

 The rectified capsules are delivered body end first
into the upper portion of split bushings or split
filling rings

 A vacuum applied from below pulls the body

down into the lower portion of the split bushing

 The diameter of the bush is too large to allow

them to follow body

 The split bushings are separated to expose the

bodies for filling

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FILLING
 Auger fill principle: Because the auger
mounted in the hopper rotates at a constant rate,
the rate of delivery of the powder to the capsules
tend to be constant
 Flat blade auger

 Screw auger

E.g. Capsugel type 8 filling machine

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Auger-Filling equipment

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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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 Piston tamp principle:

 In this, pistons or tamping pins lightly compress

the individual doses of the powders into plugs
(also called as slugs) and eject the plugs into
empty capsule bodies
 DOSATOR PRINCIPLE

 DOSING DISC PRINCIPLE

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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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DOSING DISC PRINCIPLE: a solid brass ‘stop’ plate

is sliding down the dosing disc to close off the hole.
Five sets of pistons compress the powder into cavities
to form plugs

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Dosing –disc machines

Dosing Disk

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SEMIAUTOMATIC CAPSULE-FILLING MACHINE.

(A) “SANDWICH'' OF CAP AND BODY RINGS POSITIONED UNDER RECTIFIER TO RECEIVE EMPTY
CAPSULES. VACUUM IS PULLED FROM BENEATH THE RINGS TO SEPARATE CAPS FROM BODIES.
(B) BODY RING IS POSITIONED UNDER FOOT OF POWDER HOPPER FOR FILLING.
(C) AFTER FILLING THE BODIES, THE CAP AND BODY RINGS ARE REJOINED AND POSITIONED IN
FRONT OF PINS. THESE PINS PUSH THE BODIES TO ENGAGE THE CAPS.
(D) THE PLATE IS SWUNG ASIDE AND THE PINS ARE USED TO EJECT THE CLOSED CAPSULES

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OSAKA MODEL R-180

SEMI AUTOMATIC CAPSULE
FILLING MACHINE

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AUTOMATIC FILLING
Equipments used are:
 Hofliger-Karg machine:
 Formation of compacts in a die plate using tam ping pins to
form a compact.

 Zanasi or Martelli encapsulator:

 Forms slugs in a dosator which is a hollow tube with a
plunger to eject capsule plug.

 Eli-Lilly and Co
 Farmatic
 Parke-Davis

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HOFLIGER KARG AUTOMATIC ZANASI AUTOMATIC

CAPSULE FILLING MACHINE CAPSULE FILLING MACHINE

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MECHANICALLY INTERLOCKING CAPS AND BODIES

Interlocking rings or bumps molded into the cap

and body side-walls
 ➨Posilok (Shionogi)

 ➨Snap-Fit and Coni-snap (Capsugel)

 ➨Lox-it (Pharmaphil)

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CLEANING AND POLISHING CAPSULES

Small amount of powder may adhere to the
outside of capsules after filling. It can be cleaned
and further polished by any available technique:
 Salt Polishing: Using sodium chloride

 Cloth Dusting: Capsule are rubbed with cloth.

 Brushing: Capsule are passed under soft

rotating brush.
 Pan Polishing: Acela-cota pan is used to dust
and polish.

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CAPSULE AUTO MATIC

POLISHING CAPSULE
MACHINE ARRANGEMNT

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Capsule sorT / polisH equipmenT

Rotosort
Vericap 1200
PM 60
Erweka KEA dedusting & polishing machine
Rotoweigh
Scidenader

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STORAGE, PACKAGING AND STABILITY

 Finished capsules normally contain an
equilibrium moisture content of 13-16%.
 < 12% MC, the capsule shells become brittle

 >18% make them too soft

 To maintain a relative humidity of 40-60%, when

handling and storing capsules.
 QUALI-V, developed by Shionogi Qualicaps, is
the first HPMC capsule developed for eventual
use in pharmaceutical products.

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NJP-3000,3500 SERIES AUTOMATIC

CAPSULE FILLING MACHINE
 It comply with volume-produce.
 This machine adopts full sealed
filling and turret parts and easy to
clean,
 Upper and lower die assemblies
move in one-way, imported double-
lip sealing ring made of
polyurethane and have high
performance,
 Die assemble cleaning work station
combine blowing and breathing to
ensure no powder in die hole during
high speed running.

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Dr. GSN Koteswara Rao, KLU 20

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PROBLEMS IN PRODUCTION
Extremely soluble drug.
Hygroscopic medicament.
Materials reactive to gelatin.
Large & crystal shaped powder.
Ingredients having different properties.
Low melting point of Ingredients.
Low density & high dose drug.
Liquid materials can not be used.
Encapsulation problems.
Problems during stability test.
Limited capacity of the machine

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Dr. GSN Koteswara Rao, KLU 21