 Zulcaif Ahmad


"Capsules are solid dosage forms in which
one or more medicaments are enclosed
in a water soluble bio degradable shell
made up of gelatin"
Hard- shelled capsules

Soft-shelled capsules
 “Hard-shelled capsules,
which are typically made
using gelatin and contain
dry, powdered
ingredients”

These are made in two halves:

 Lower-diameter "body" that
is filled
 Then sealed using a higher-
diameter "cap".
Soft-shelled capsules,
primarily used for oils
and for active
ingredients that are
dissolved or
suspended in oil.
Capsules Are Made From Aqueous Solutions Of
Gelling Agents Like:

Animal protein, mainly gelatin

Plant polysaccharides or their derivatives like
carrageenans and modified forms of starch and cellulose.
Other ingredients can be added to the gelling agent
solution like:
plasticizers such as glycerin or sorbitol to
decrease the capsule's hardness,
coloring agents,
preservatives,
disintegrants,
Lubricant
surface treatment
1. Gelatin
2. Certified dyes
3. Sugar
4. Water - 12 to 16 % but may vary depending on the
storage condition
5. Sulfur dioxide (0.15%) - prevent decomposition
during manufacture
6 Opaquants /Opacifying agent - titanium dioxide
 Gelatin or gelatine (from Latin: gelatus
meaning "stiff", "frozen") is a translucent,
colourless, brittle (when dry), flavourless
foodstuff, derived from collagen obtained from
various animal by-products.
 It is commonly used as a gelling agent in food,
pharmaceuticals, photography, and cosmetic
manufacturing.
 Gelatin is an irreversibly hydrolyzed form of
collagen
TYPE A
Derived from acid treated precursor that exhibits an
iso electric point at pH-9. It is manufactured mainly
from animal bones
TYPE B
Derived from alkali treated precursor that exhibits an
iso electric point at pH-4.7. It is manufactured
mainly from pork skin
 HARD GELATIN CAPSULES

• Also referred to as “DFC” Dry Filled Capsule.

CAPSULE SIZES:
•For human use, empty capsules ranging in size from 000 (the largest) to
5
•(the smallest) are commercially available.
•Generally encapsulates between 65mg to 1g of powdered material.

•For veterinary use: No's 10, 11and 12 having capacities of 30, 15 and
7.5 g, respectively
 Ease of use due to the fact that it is smooth,
slippery and easy to swallow.
 Suitable for substances having bitter taste and
unpleasant odor.
 As produced in large quantities it is economic,
attractive and available in wide range of
colors.
 Minimum excipients required.
 Little pressure required to compact the
material.
 Unit dosage form.
 Easy to store and transport.
 Not suitable for highly soluble substances
like potassium chloride, potassium
bromide, ammonium chloride, etc
 Not suitable for highly efflorescent or
deliquescent materials.
 Special conditions are required for
storage.
MANUFACTURING OF HARD GELATIN CAPSULES

Steps involved in making empty gelatin capsules

with peg/pin method…

1.Dipping
2.Spinning
3.Drying
4.Stripping
5.Trimming and Joining
6.Polishing

The process of capsule shell production with the pin method:

• Dipping→ Drying → Stripping→ Trimming→ Joining →
Polishing
• DIPPING :
Pairs of the stainless steel pins are dipped into the dipping solution to
simultaneously form the caps and bodies.
The dippin solution is maintained at a temperature of about 50 degree
centigrade in a heated ,jacketed dipping pan.

• SPINNING:
The pins are rotated to distribute the gelatin over the pins unifomly and to
avoid the formation of a bead at the capsule ends.

• DRYING :
The gelatin is dried by a blast of cool air to form a hard shells.
The pins are moved through a series of air drying kilns to remove water

• STRIPPING :
A series of bronze jaws strip the cap and body portions of the capsules
from the pins.
 TRIMMING AND JOINING

• The stripped cap and body portions are trimmed to the

required length by stationary knives.
• After trimming to the right length, the cap and body
portion are joined and ejected from the machine.

POLISHING
Pan Polishing : Acela-cota pan is used to dust and polish.

Cloth Dusting : Capsule are rubbed with cloth.

Brushing : Capsule are feed under soft rotating brush.

• During production the thickness of the capsule wall is controlled by the viscosity
of the gelatin solution, speed and time of dipping.
• Empty capsules should not be subjected to temperature above 38 ºC
(might destroy the capsule shells such that they can not be handled in the
Filling equipments)
• Empty capsules should maintain moisture Content between 12% and 15%.
Below 10% they become brittle
Above 16% they might increase in size (causing problems inthe filling
equipment) or they might become soft.
 CAPSULE FILLING MACHINE
It is the mechanical device that fills the powders
(active ingredients and the mixtures of active
ingredients with combinations of different
excipients) into hard or soft gelatin capsules.

Capsule filling machines are used commonly in

industrial and pharmaceutical purpose. Millions
of capsules can be filled by using different
varieties of capsule filling machines which are
provided by different manufacturers.
 Hard capsule FILLING

1) Bench scale filling.(for small scale filling)

- Manual filling machine
eg: feton capsule filling machine
2) Industrial scale-filling.
Comes in varying shapes and sizes
- semi automatic machine
- fully automatic machine
• At present about 9 manufacturing companies supplies the
capsule filling machines with different models . The following
famous companies which provides capsule filling machines are
 Eli Lilly and company indianapolis IN
 Farmatic SNC, Bologna, Italy
 Macofar SAS, Bologna, Italy
 Hofliger and Karg, Waiblingen, Germany
 mG2 S.P.A., Bologna, Italy
 Osaka, Osaka, Japan
 Parke-Davis and company, Detroit, MI
 Perry Industries, Green BayWI
 Zanasi Nigris, S.P.A., Bologna, Italy

The largest number of total machines are supplied by Lilly and

Parke-Davis. The method of operation and the description of
the machines are similar in these two companies.
The nine famous companies which provides capsule filling
machines of different models and types are as follows:

 Lilly capsule filling machine, Lilly ROTOFIL capsule filling machine.

 Farmatic Model 2000/15, 2000/30 and 2000/60 capsule filling machine.

 Hofliger and Karg model GKF-303, GKF-602, GKF-1500 and GKF-2500

capsule filling machine.

 Macofar:MT-12, MT-13/1 and MT-13/2 capsule filling machine.

 mG2:Model G36/4, G36/2, G36, G37N and G38 capsule filling machine.

 Osaka Model 180 capsule filling machine.

 Perry: Perry Model CF ACCOFIL capsule filling machine.

 Zanasi:Zanasi Model LZ-64 and AZ-20 capsule filling machine

What is the common working principle of all capsule
filling machines?
 Bench scale filling

Sealing plate with rubber top Pin plate with 200-300 holes

Bed – 200-300 holes

Cam handle
Powder tray

lever
loading tray
with 200-300 scraper
holes
 HAND OPERATED CAPSULE FILLING MACHINE

It consist of a bed having 200-300 hole, a loading tray having

200-300 holes, a powder tray, a pin plate having 200-300 pins,
a sealing plate having a rubber top, a lever, a cam handle.
The empty capsules are filled in the loading tray and it is
palced over the bed. The cam handle is operated to separate
the capsule caps from their bodies.

 The powder tray is placed in a proper position and filled with

an accurate quantity of powder with scraper. The excess of the
powder is collected on the platform of the powder tray. The pin
plate is lowered and the filled powder is pressed by moving the
pin downwards.
After pressing the pin plate is raised and the remaining powder is filled into
the bodies of the capsules. The powdered tray is removed after its
complete filling. The cap holding tray is again placed in position. The plate
with the rubber top is lowered and the lever is operated to lock the caps
and bodies. The loading tray is then removed and filled capsules are
collected.

With a 200 hole machine, about 5000 capsules can be filled in one hour,
whereas in a machine having 300 holes, about 7500 capsules can be
filled in one hour.
• JAANSUN CAPSULE FILLING MACHINE
There are 3 stations in
this semi-automatic
capsule filling
machine
 orientation of
capsule
 powder filling
 capsule closing.
The functions of first station include :
1. capsule feeding
2. Aligning
3. insertion into bores of holding ring
4. vacuum is used for separating capsule cap
and body in first station.
5. After orientation of capsule, capsule cap
can stay in upper holding ring and capsule
body can stay in lower holding ring.
 THE SECOND STATION:POWDER FILLING

Separate the holding ring,put the lower (body) holding

ring on the rotary table, pull the powder hopper over the lower
(body) holding ring, then auger inside powder hopper starts to run
and fill powder into the capsule body.
While Iower holding ring turns one circle, push powder hopper
to its original psition.
 THE THIRD STATION:CAPSULE CLOSING

Put upper holding ring and lower holding ring

together, then position intact holding ring in
front of peg ring .closing plate is pivoted to a
position approximately 180 degrees
Pneumatic pressure is applied to peg ring
which finally push capsules inside the bores
of holding ring the finished capsules will be
collected into the container.
Lilly/Parke-Davis
Storage hopper

Rectifying unit

Two piece filling ring

Powder hopper

Peg ring

Closing plate

Collecting chamber
• SEMI AUTOMATIC MACHINE
 AUTOMATIC CAPSULE FILLING MACHINE

• Automatic Capsule Filling Machine has been designed

and developed to fill hard gelatin capsules with
powder or pellets. It is an extremely durable and
reliable machine that fills dosages to the highest
accuracy. It can be applicable to the widest range of
capsules at all sizes and guarantee the integrity of all
capsules.
Fully automatic
 The housing and surface are covered with stainless
steel 304. All contact parts of medical powders are
made from a corrosion resistant stainless steel 316.
 Parts are made by CNC computer machine. All parts
are standardized and easy to substitute.
 Capable of filling 6 capsules at a time with operation
from 10 stations. Accurate operation for orientation,
opening, filling, joining and ejecting of the capsules
 Compulsory spiral feeding in the powder hopper to
ensure powder feeding and filling.
 Dual capsule-opening design to ensure all capsules
are opened.
 Electrical impact protection device to prevent any
further damage. The machine will stop automatically
in the event of collision.
 Safety Sensing System to shut the machine down
automatically in the event of problems when no
capsules, no powder, door is opened, and abnormal
load for the machine are detected.
 Automatic vacuum removal of the air in the
dosing tube to give more accurate weight of the
filled capsules.
. Exclusive dosing tube system, temperature of the
powder will not rise during the filling process.
 Adjustable compression piston in dosing trube to
adjust the powder volume without change parts.
 FARMATIC SNC

Farmatic offers three models of filling equipments

Model capacity

2000/15 40000 capsules

per hour
2000/30 80000 capsules
per hour
2000/60 160000
capsules per
hour

Farmatic Model 2000/60

Capsule filling machine
 Hofliger and Karg

H & K line consists basically of

four machine models.

GKF-303
GKF-602
GKF-1500
GKF-2500

HOFLIGER KARG AUTOMATIC

CAPSULE FILLING MACHINE
 Empty capsule storage hopper

Rectifier

Bulk powder storage hopper

Capsule body transport segment

Closing station

Filled capsules ejection station

H & K model GKF-602

 Macofar

• Macofar line of equipments consists of three models.

• Low to medium capacity machines

MODEL CAPACITY
MT-12 35,000 capsules per hour
MT-13/1 5,000 capsules per hour
MT-13/2 10,000 capsules per hour
 mG2
• Five models of continuous motion filling machines are
offered by mG2.

MODEL CAPACITY

• G36/4 150 capsules per minute

• G36/2 300
• G36 600
• G37N 1600
• G38 1000
 OSAKA
High capacity, continuous motion machine.

The only model available is

R-180 : 70000 to165000 capsules per hour

Can be modified to 400000 capsules per hour.

 OSAKA MODEL R-180
SEMI AUTOMATIC CAPSULE
FILLING MACHINE
 ZANASI

• Nine different units in four model lines

• LZ-64 : 4000 capsules per hour
• AZ-20 : 9000 TO 20000 capsules per hour
• BZ series
• BZ-40 : 30000/hr
• BZ-72 : 60000/hr
• BZ-110 : 110000/hr
• BZ-150 : 150000/hr
• Z-5000 series
• Z-5000-R1 : 70000/hr
• Z-5000-R2 : 110000/hr
• Z-5000-R3 : 150000/hr
 ZANASI AUTOMATIC
CAPSULE FILLING MACHINE
 MANUAL FILLING METHOD(PUNCH
METHOD)

 HAND OPERATED METHOD

 AUTOMATIC OPERATED FILLING

MACHINES
 Used for filling a small number of capsules in the
pharmacy, at the prescription counter.
 The ingredients are triturated to fine & uniform powder.
 The powder is placed on a powder paper or ointment slab
and smoothed with a spatula to a height approximately
half the length of the capsule body
The base of the capsule is held vertically and the open end is

repeatedly pushed or "punched" into the powder until the capsule is

filled;
The cap is then replaced to close the capsule. Each filled capsule is

weighed using an empty capsule as a counterweight.

Powder is added or removed until the correct weight has been

placed in the capsule.

The filled capsule is tapped so that no air spaces are visible within

the contents
 Pharmacists that prepare capsules on a regular or extensive basis

may use hand-operated capsule machines.

 These machines are available in capacities of 24, 96, 100, and 144

capsules.

 machine is the tray used to hold the fill over the empty

capsules, the spreader and roller used to distribute the fill

material in the tray and permit it to enter the capsules uniformly,

and the packer used to compact the fill in the capsules

 Machines developed for industrial use can
automatically remove the caps from empty capsules,
fill the capsules, replace the caps, and clean the
outside of the capsules at a rate of up to 1,65,000
capsules and greater per hour.
 TAMPER-EVIDENT CAPSULES are made sealing the joint
between the two capsule parts.

 DISTINCTIVE LOOKING CAPSULES can be made by

sealing capsules with a colored band of gelatin, which
cant be restored without expert sealing.

 HEA T WELDING PROCESS can also be used, that fuses

capsules cap through the double wall thickness at
junction

 LIQUID WETTING AGENT that lowers the M.P in contact

areas of capsule cap & body & then thermally bonds
the two parts using low temperatures
A recent innovation in capsule
shell design, where the two
halves of the capsule shells are
enable to be positively joined
through locking grooves in the
shell walls.
The two grooves fit into each
other and ensure reliable closing
of the filled capsule.
Opening of such capsule is
difficult with increasing security
of the contents of the capsule
 On small scale capsules may be cleaned
individually or in small numbers by rubbing
them with a clean guaze or cloth.
 On large scale many CAPSULE FILLING
MACHINES with a cleaning vacuum that
removes any extraneous material from the
capsule as they exit the equipment.
 (ACCELACOTA APPARATU..S)
 Hard gelatin capsules are stored in a tightly
closed glass or plastic containers, protected
from dust and extremes of humidity and
temperature.
 Mini Ideal Maximum
mum
Relative humidity 40% 50% 60%

Temperature 15 0c 20oc 25oc

These capsules contain 12 - 16% water but water
content vary according to the storage conditions.
Capsules become brittle in low humidity but are
flaccid and lose their shape if stored in high
humidity.
They do not protect hygroscopic materials from
atmospheric water vapor as moisture can diffuse
through the gelatin wall. When storage temperature
condition is high the quality of the hard gelatin
capsules are affected
 Simpler manufacturing process.
 Fewer production steps
 Less manufacturing equipments.
 Reduces stability problems with sensitive
drugs.
 Granules, powders, liquids, semi-solid
formulations and mini tablets can easily be
filled alone or in combination.
 Reduces stability problems with sensitive
drugs.
 Printing options, axially or radially, provide
greater possibilities in branding protection
 <<<SOFT
GELATIN
CAPSULES>>>>>
“ Soft gelatin capsules are one piece ,
hermetically sealed , and are made up
of gelatin in which glycerin or polyhydric
alcohol (sorbitol) are added , containing
liquid , suspension or semisolid enclosed
in matrix.”
 They may be oblong,

oval, or round.

 They Vary in sizes

 They may be single

colored or two

toned
 Drug present in these capsules may be suspension,
solution or emulsion

 Ingredients that are solid at room temperature can

also be encapsulated in softgels if they are at least
semisolids below 45degree.

 The softgels can be coated with enteric resistant or

delayed release coating material.
 The capsule shell is basically composed of Gelatin, a
plasticizer & water it may
contain additional ingredients such as preservative,
coloring & opacifying agents, flavorings, sugars, acids &
medicaments to achieve desired effects

1. Capsule shell WATER:

NOT MORE THAN 45% w/w the ratio by
weight of water to dry gelatin can vary from 0.7
to1.3(water) to 1.0(dry gelatin) depending on the
viscosity of the gelatin being used.

2. PLASTICIZER:
Used to make the soft gel shell elastic & pliable.
Ratio used is between 0.3 to 1.8 for soft to hard shell on
dry basis. E.g. glycerin , sorbitol
3.COLOUR:
Used in shell has to be darker than colour of
encapsulating material colours may be natural or
synthetic.

4.OPACIFIER:
Usually titanium dioxide, may be added to produce
an opaque shell ,when the fill formulation is a
suspension or to prevent photo degradation of light
sensitive fill ingredients. Concentration of opacifier
may be up to 0.5%

5.Chelating Agents:
Iron is always present in raw gelatin, & should not
contain iron more than 15 ppm.
Additionally chelating agent may be used for
preventing the reaction of iron with
materials or colours.
A typical gel mass formula for making soft
gelatin capsules would be:

 Gelatine 35-45%
 Plasticizer 15-25%
 Water ~40%
 Dye / Pigment as needed
 Opacifier as needed
 Other (flavor, sugar,) as needed

(((1 part gelatin, 1 part water, 0.4-0.6 part

plasticizer)))
 >The gel is prepared in a 300-litre stainless
steel vessel
 >Gelatin powder is mixed with water and
glycerine. Heating. Stirring. The molten
gelatin mass is formed
 >It is decanted into 200-kg mobile vessels
 >Turbine mixing where colours and flavours
can be added. It ensures consistency of
gelatin mass
 >This mass is kept at a constant
temperature until it is needed for the next
stage of the process
 Content may be liquid, or a combination of
miscible liquids
 Solution of a solid(s) in a liquid(s) or
Suspension of a solid(s) in a liquid.
 It can be a liquid like a volatile oil
composition E.g. Vegetable oils like arachis
oil or aromatic or aliphatic hydrocarbons,
ethers, esters, or alcohols.
 Solids that are not Sufficiently soluble in
liquids or in combination of liquids are
capsulated as Suspension. Suspending
agents used are Lecithin, Soyabean oil,
yellow wax
 Types of softgels
 Orally administered: Solutions or
suspensions that release contents in
stomach.

 Chewable softgels: Highly flavored shell

is chewed to release drug liquid fill
matrix.

 suckable softgels: gelatin shell to be

sucked & liquid matrix or just air inside
capsule

 Meltable softgels: meltable softgels are

used for pessaries or suppositories.
1.plate process:
 It involves pressing 2 sheets of wet gelatin together
b/w 2 molds.

 Each die mold contained pockets into which gelatin

sheet was pressed & into which medication was filled.

 Pressure b/w 2 plates enable each capsule to cut out

from mold & capsules were subsequently dried.

*Robert P scherer in 1933 invented this
method
*the material to be encapsulated flows by
gravity
<<Principle>>
“Involves the formation of a heat seal b/w
two gelatin ribbons, simultaneous with
dosing of fill liquid into each capsule”
Before encapsulation, two processes
are carried out:
1. Gell mass (providing softgel shell)
2. Fill matrix (for softgel contents)

GELL MASS
prepared by dissolving gelatin in water at
approx, 80 degrees under vacuum and addition
of plasticizers ( glycerol)
* once gelatin is fully dissolved then other
components are added (colorants, flavourants,
preservatives)
 molten gel is pumped to machine and two thin ribbons of gelatin formed.
*thickness of each gel ribbon is controlled in range of 0.5-1.5mm*

Ribbons pass over rollers and are fed between

two rotating die cylinders that determine the size and shape of capsules,
forming two halves of capsule

ribbons converge next to a fill injector

Here appropriate volume of fill

material is measured and dispensed by a pump

die assembly rotates, filled capsule halves sealed together by

heat and pressure application and ejected
 drying in tumblers containing lint-
free towels and large volume of forced air

Capsules transferred To trays and placed in low-

humidity drying rooms, at room temp, to remove excess moisture

water content of the gelatin shell at start ---around 30%

water content of the gelatin shell when evaporation end -- 8 or 9%
The following should be monitored/controlled:
 Gelatin temperature
 Fill temperature
 Ribbon thickness
 Seal or seam width
 Fill quantity
 pressure ( b/w rotary dies, controls softgel
shape and final cut out from gel ribbon
Typical Parts Of Machine
1.Spreader Box
2.Cooling Drum
3. Oil Lubrication Roller
4. Gelatin Ribbon Guide Roller
5.Die Roll
6.Injection Wedge
7.Capsule Stripper
8.Conveyor
9.Medicine Filling Hopper
10.Medicine Filling Pump
Or Stern machine, uses a system of rotary dies but is
unique in that it is only machine that can
successfully fill dry powder into a soft gelatin
capsule.
 Measuring roll rotates directly over the die roll, and
the pockets in the 2 rolls are aligned each other.
 Measuring roll-powder or granular fill material
under vacuum.
 Die roll-plasticized sheet under vacuum Sealing roll-
second gelatin sheet applied to form other half of
capsule Pressure developed between die roll and
sealing roll seals and cuts out the capsules
1.Uniformity of dosage unit
2.uniformity of content
3.uniformity of mass
4.dissolution
5.Storae
6.labelling
1. gel ribbon thickness and uniformity
across the ribbon
2. seal thickness
3. weight of capsule fill and its variation
from capsule to capsule
4. weight of capsule shell and its variation
from capsule to capsule
5. moisture level of the capsule shell
before and after drying
1. Permeability and sealing
2. potency and impurity content
3. average weight and weight variation
4. uniformity of content
5. disintegration
6. dissolution
7. moisture content
8. microbial content
1. permeability and sealing:
capsules are tested for physical integrity, by
visual inspection like, absence of breakage or
open cap and body

2. POTENCY AND IMPURITY CONTENT:

All capsules are tested for drug contents, as
well as impurities and other substances must
meet pre-defined specifications for a batch
to be acceptable
 FOR HARD CAPSULES:
20 capsules are individually weighed Test

complies if individual capsule falls with in 90-

110% of average weight
 capsules are tested to ensure lack of
growth of bacteria and mold by
microbiologiocal testing.
 test is carried out by incubating the
capsule contents in growth medium and
counting colonies formed after pre-
defined period of time.
 Pharmaceutical Dosage Forms and Drug
Delivery, Second Edition By Ram I. Mahato
 http://www.pharmacopeia.cn/v29240/usp29
nf24s0_c711.html
 http://www.authorstream.com/Presentation/aSG
uest89715-887369-soft-gelatin-capsules/
 http://www.slideshare.net/Ramyapriya7/quality-
control-of-capsules