Project Work

06/01/2022

TITLE: PRODUCTION OF TABLETS AND CAPSULES

This project report was submitted for in partial

fulfillment of requirements for the Degree of
Bachelors of Pharmaceutical Technology (B.
Pharm)
2018-2022

By

Sudip Dandapat
University Roll No: 24201918021
College Roll No. 18113
Registration No. 182420210092 of 2018-2022

Under supervision of
Dr./Prof: - Mr. Souparna Paria
Faculty of B. Pharm
Bengal College of Pharmaceutical Sciences &
Research
Bidhannagar, Durgapur, West Bengal 713212

[1]
Introduction
In the world of pharmacy, administration through
the oral route is one of the most important parts out there.
Where the Parenteral route of administration (Mostly
Injections) are better for emergencies Nevertheless, All the
drugs used to produce systemic effects, 90% of them are
administered by the oral route. In the present state, the two
most important candidates of oral drug administration are
Tablets and capsules. So, what are the Tablets? A tablet is an
oral dosage form to define a solid dosage unit form consisting
of a mixture of active and auxiliary substances, usually in
powder form, pressed or powdered from a powder into a
solid dose. And on the other hand, Capsules are a form of a
solid dosage form in which a drug or drug mixture is enclosed
in a Gelatin Shell or any other suitable substance to create a
variety of shapes. The machinery involved with Tablet and
Capsule production is improving year by year, but still, the
main generalized idea remains the same.

In the coming pages, I am going to explain the production of

Tablets and the Production of Capsules in two parts. Which
are
1. The Production of Tablets
2. The Production of Capsules

[2]
 1. The production of Tablets
o Types of tablets
Before getting into production we have to know the types of
tablets that are presently consumer-available right now.

i. Compressed Tablets
These tablets are formed of Compression of powdered
crystalline, or granular active materials (API) alone or with a
combination of certain excipients as required, such as
binders, disintegrants, sustained-release polymers,
lubricants, diluents, flavors, and colorants. Based on these
excipients the compressed Tablets are further divided into: -
a. Sugar-coated tablets (SCT)
b. Film-coated tablets (FCT)
c. Enteric-coated tablets (ECT)
d. Multi compressed tablets (MCT), involve more than
one compression cycle.
d.1 Layered tablets
d.2 Press coated tablets
e. Sustained-release tablets
f. Tablets for solution
g. Effervescent tablets
h. Compressed suppositories or inserts
i. Buccal and sublingual tablets

ii. Molded tablets or tablet triturates (TT)

Tablet triturates are usually made out of moist material using
a mold which gives it the typical shape of a tablet and the cut
[3]
 section of the cylinder. These are made to be quickly and
completely soluble, so suitable water-soluble lubricant is a
constraint most of the time while production of such tablets.

iii. Dispensing Tablets (DT)

Such tablets provide a convenient quality of potent drug that
can be transformed into powders and liquids readily without
any hassle. These tablets generate the need of weighing
small quantities. They are not dispensed as a dosage form
but these provide convenience for extemporaneous
compounding.

iv. Hypodermic Tablets (HT)

These are soft and readily soluble tablets. These are mostly
new in terms of formulation methods and are not yet vastly
used.

o Tablet Processing
All over the world, Pharmaceutical Products are processed
using Direct compression, Wet granulation, or dry
granulation methods. Which method to be used in the actual
production is decided by the ingredients’ individual
characteristics like flow property, compressibility, etc. The
right choice of method requires a thorough investigation of
each
Active
Ingredient
Mixing and
Drying Compression Coating Pakaging
Granulation

Excipients
Fig.1. Various Unit Operation Sequences in Tablet Manufacturing
[4]
ingredient to be used in the formula for a comprehensive
approach for interactions and stability.

i. Direct Compression
In this method, we directly compress the powdered materials
into tablets without modifying the physical nature of the
materials. This method is generally done for crystalline
materials having good physical properties. By good physical
property, I mean materials having good flow property,
compressibility, etc. It is a time-saving and low-cost-
consuming operation.

ii. Wet Granulation

In tablet preparation, this is the most widely used method. In
this method, some kind of binder is used according to the
purpose it is used and the kind of API to be formulated with
to achieve adhesion between the power molecules. The
binder is added by diluting with a suitable solvent before
adding to the blended powders, to form wet granulation
which in turn are dried suitably to expel the solvent forming
dried granules. The responsible candidate for granules
formation is the surface tension forces and capillary pressure.
It only becomes advantageous when all the requirements for
the tablet formation though it is a multistage operation and
time-consuming.

iii. Dry granulation

The dry granulation process is used to form granules without
using a liquid solution. This type of process is more

[5]
preferable for the production of moister and heat-sensitive
products. Moisture-less granules formation requires
compacting and densifying the powders. Dry granulation can
be done on a tablet press using slugging tooling. On a large-
scale roller, a compactor is also known as a chilsonator. The
compacted mass is called slugs and the process is known as
slugging. Then the slugs are milled to produce a granular
form of tablet materials, with have better flow properties
than the original powder mixture. The main advantage of dry
granulation is it requires less equipment and eliminates the
addition of moisture and the application of heat, as found in
the wet massing and drying steps of the wet granulation
method. The manufacturing of oral dosage forms such as a
tablet is a multi-stage complex process where starting
materials change their physical characteristics multiple times
before reaching their final dosage form. If we look at the
Traditional way, tablets have been made by granulation
process, which imparts two primary required characteristics
to formulate: compactibility and fluidity. In both wet and dry
granulation (slugging and roll compaction) are used.
Regardless of whether tablets are made by direct
compression or granulation, the first step being milling and
mixing is the same; later on, steps may differ. There are
numerous unit processes are involved in making tablets,
including particle size reduction and sizing, blending,
granulation, drying, compaction, and (frequently) coating.
There are various factors associated with these processes can
seriously affect content uniformity, bioavailability, or
stability.
[6]
Wet granulation Dry granulation Direct
compression
1. Milling and mixing 1. Milling and 1. Milling and
of drugs and mixing of drugs mixing of drugs
excipients and excipients and excipients
2. Preparation of 2. Compression 2. Compression
binder solution into slugs or roll of tablet
compaction
3. Wet massing by 3. Milling and
addition of binder screening of slugs
solution or and compacted
granulation solvent powder
4. Screening of wet 4. Mixing with
mass lubricant and
disintegrants
5. Drying of the wet 5. Compression of
granules tablet
6. Screening of dry
granules
7. Blending with
lubricant and
disintegrants to
produce “running
powder”
8. Compression of
the tablet.
Table.1. Typical Unit Operation involved In Wet Granulation, Dry Granulation and Direct
Compression

Now the granulation techniques are all warped up, I can

discuss some important procedures in detail next.
[7]
 o Dispensing (weighing and measuring)
In any pharmaceutical manufacturing process dispensing is
the first step. It is one of the most critical steps in
pharmaceutical manufacturing; during this step, the weight
of each ingredient in the mixture is determined according to
dose. This procedure may be done purely manual by hand
scooping from primary containers and weighing each
ingredient by hand on a weight scale, by manual weighing
with material lifting assistance like Vacuum transfer and Bag
lifter, Manual of assisted filling of a loss-in-weight dispensing
system, automated dispensaries with mechanical devices
such as vacuum loading system and screw feed system.
Issues like weighing accuracy, dust controlling system, during
manual handling, lot control of each ingredient, material’s
movement in and out of dispensary should be monitored
during dispensing.

o Sizing
In this important step the size reduction milling, crushing,
grinding, pulverization is done, in compressed tablet
manufacturing the mixing or blending of several solid
ingredients of all solid ingredients in an easier, and more
uniform way is must be achieved, so that all the ingredients
get to the same size. This provides a uniform dose. In the
case of lubricant mixing, the granules' fine particle size is
essential for proper function.

Some advantages of size reduction are –

[8]
 a. Helps to increase the surface area, which can enhance
the active ingredient’s dissolution rate and hence
bioavailability.
b. The tablet-to-tablet content uniformity gets Improved as
the particle number increases per unit weight.
c. Controlling particle size distribution will also promote
better flow of mixture in dry granulation tablet machine.
d. Better Flow properties of raw materials.
e. Enhanced dye or API dispersion in tablet excipients.
f. Uniform sized particles in the wet granulation method
promote uniform drying.

There are some disadvantages as well.

a. There immerges a chance of possible change in the
polymorphic form of the API, rendering it less or inactive or
unstable.
b. Decreased bulk density of API or Excipients, may cause
flow problems and segregation in the mix.
c. The surface area expansion from size reduction may
promote air adsorption which may inhibit the wettability of
the drug to the extreme limit so that it becomes the limiting
factor in dissolution rate.

Different types of machines may be used in the dry sizing or

milling process depending on if gentle screening is needed or
particle missing is needed. The equipment range includes
Fluid energy mill, Colloidal mill, Ball mill, Hammer mill,
Cutting mill, Roller mill, Conical mill, etc.

[9]
 o Powder Blending
Unlike a liquid, where we can easily
achieve the perfect homogeneity,
the powder mixing to that level of
perfection is practically unattainable.
Which makes it a more difficult unit
operation. In practice, problems also
arise because of the inherent
Fig.2. ’V’ blender
cohesiveness and resistance to
movement between each particle. The
process gets more complicated further
ahead in many systems. The presence
of substantial segregation influences
the powder mix. It arises because of
the difference in size, shape, and
density of the component particles.
Every mixing process has its optimum Fig.3. Tumble Blender
mixing time and so Prolonged mixing may
result in undesired product behavior. That’s why optimum
mixing time and mixing speed are evaluated. Prior
compression blending step is normally achieved in a simple
tumble blender. The blender may be fixed, into which the
powders are charged, blended, and discharged. To use a bin-
blender which blends in now getting common to use. Special
monitoring is needed in special cases like lubricant mixing.
Various types of blenders include “V” blender, Container
blender, Oblicone blender, Agitated powder blender,
Tumbling blender etc. But nowadays to get more efficient in
manufacturing through wet granulation the blenders are
[10]
mixing the processing steps like mixing, granulation, and or
drying. This kind of granulation method is known as “Mixer
granulator” or “High Shear mixing machine”.

o Granulation
Following particle size reduction and blending, the
formulation might be need to be granulated to be made
homogeneous.

o Drying
To keep the moisture low, to prevent product deterioration
and to ensure free-flowing properties, drying step is used.
Some commonly used dryers are- Bed dryer, Vacuum tray
dryer, Microwave dryer, Spray dryer, freeze dryer, Turbo -
Tray dryer, Pan dryer, etc.

o Tablet compression
After the granule formation (wet granulation) or mixing of
the ingredients (direct compression) or sized slugs (Dry
granulation), the particles are compressed to get the final
product. It is done by either a single punch machine (e.g.
Stamping press) or by a multi-station machine (e.g. rotatory
press). Tablet compressor is a high-speed compression
device. It can press tablet ingredients with extreme precision.
These machines are capable to produce tablets in various
shapes but most of the time they are round or oval. Also, it
can press the manufacturer or product name into the tablet.
Each of the tablets is made by pressing the granules inside a
mold or die, made up of strong metal substances (usually
[11]
steel). The die is disc-shaped with a hole cut through its
middle. The powder is pressed in the middle of the die by
two strong steel punches that fit into the die top.

The punches and dies are fixed to a turner. As the turner

spins (mechanically mostly or by hand in small scale) the
punches are driven together by two fixed cams – upper and
lower cam. On the upper cam edge sits the punch head. On
the lower cam edge, the bottom of the lower punch sits. The
two cams' shapes determine the sequence of movements of
the two punches. This process gets repeated each time the
turner spins.

Pressure on the tablet press is controlled and monitored to

make tablet perfect. Being high-speed machinery, they are
needed to be lubricated, and to do so they are fitted with a
recycling lubricating system for consistent lubricant supply.

Auxiliary Equipments for tablet compression:

i. Granulation Feeding Device: Sometimes the die table
speed gets so high that the time of die under feed
frame becomes too short. Results Inadequate or
inconsistent gravity filling of die with granules, which
leads to weight variation in tablets and ununiformity.
These kinds of things can also be seen with poorly
flowing granules. To eliminate these problems,
mechanized feeder can employ force granules into die
cavity so the content ununiformity gets reduced by
many folds.
[12]
 ii. Tablet weight monitoring devices: When modern
press generates High rate of tablet output, A high
speed weight monitoring system becomes a
requirement. Which can monitor electronically and
accurately. Thomas Tablet Sentinel and
Pharmakontroll and Killan control system-MC are
examples of systems that can come handy in these
kinds of situations. These systems monitor the force at
each compression station by starin gage technology.
iii. Tablet De-duster: To remove
extra powders on the surface
of the tablets coming out of
press the de-duster is used.
iv. Fette machine: This device
cools down the compression
components before Fig.4. Tablet De-duster

compression so that the

compression ingredients can be compressed easily.
This kind of method is only practical when any
compression material becomes heat-sensitive or has a
relatively lower melting point. e.g. Waxes.
o Packaging
Packaging is important because the manufacturers need to
package their products (medicines) before they can be sent
out for distribution. How the packaging will happen depends
on the formulation of the medicine. “Blister packs” are the
most common form of
the packaging used for a
wide variety of tablets.
[13]

Fig.5. Blister packs

Its advantages include safe and easy usage and the customer
option availability to see the contents without opening. Many
companies have standard sizes of blister packers to avoid
machinery changing between products, and it becomes also
cost-effective. For an easy detachment of tablets sometimes
the pack is perforated. That causes the removal of the expiry
date to avoid such a problem occurring, the expiry date and
the name of the product are printed on each part of the
package.

Blister packs are made in a way so that the pack remains flat
as it travels through the packaging procedure, minimum-till it
is inserted into a carton. Such a set of requirements becomes
a critical challenge for the designers. For better stiffness,
extra ribs are added to the blister pack.

o Tablet defects
i. Mottling: When colour of the tablet gets Unequally
distributed and dark and light areas stands out on the
surface of the tablet where it should be uniform, it is
called mottling.
ii. Capping: In high speed tablet compression machine
high degree of compression setting causes tablet to
separate its main surface into individual surface. To
eliminate such problem, defective punches and dies
are suggested not to be used. High temperature can
also promote capping.
iii. Lamination: It is the biggest problem among all tablet
defects. For using of low-level binding agent or
[14]
 improper granulation method Air gets entrapped into
the tablet layers. It gets visible just after the
compression or while keeping in storage. Direct
compression doesn’t face such problems usually.
iv. Picking: The tablet ingredients can get stuck on the
tablet punch surface due to its adherence property.
To avoid such problem Wet granules are suggested
not to be pressed and colloidal silica is added as a
polishing agent as a compression ingredient.
v. Sticking: This kind of problem is seen with substances
having low melting-point, moisture also promotes this
defect, this leads to inconsistent tablets weight and
produces rough and chipping of tablet surfaces. It
leaves material of both punches. Proper drying is the
cure for this kind of problem.
vi. Weight Variation: The causes includes Improper
granule blending, lack of sufficient lubricant,
Ununiform mixing or abnormal mixing of excipients
and wrong glidant selection. To get away with these
kinds of problem size distribution uniformity and
smaller granular size control becomes necessary.
vii. Hardness Variation: Granules weight variation is the
culprit here. Anti-turning devices are used to solve
this problem.
viii. Soft Tablets: Use of ingredient that remove the waxy
nature of tablets are used to resolve this kind of
problem.

2. Production of Capsules
[15]
 o Types of Capsules
There are various types of capsules are stated in google
scholarly articles. But I’m going to simplify the all types in this
project. Capsules in modern days categorized in two types
1. Gelatin Capsules
2. Non-Gelatin Capsules
After that they are further divided in various types as showed
in the Fig.6.
Capsules

Gelatin Non-Gelatin
Capsules Capsules

Soft-Gelatin Hard-Gelatin HPMC Starch

PVA Capsules
capsules capsules Capsules Capsules

o Explanation of all types of capsules:

i. Soft-Gelatin Capsules: It was
Fig.6. Classification of Tablets
developed in 19th century to
mask unpleasant odor and taste of drug substances.
These kinds of capsules have various kind of applications
in health and nutrition products, pharmaceutical

[16]
 products, cosmetic application and even in recreational
products like creation of paintballs. Soft gelatin capsules
give some preferable applications such as high content
uniformity of low dose drugs, reduced operator and
environmental contamination with cytotoxic or highly
potent compounds. Also, soft-gelatin capsules are easy
to swallow. Some of the most interesting advances are
made in recent years are developing liquid and semi-
solid formulations in a soft gelatin capsule to get better
stability on particular bio-performance issues, better
bioavailability and lesser plasma variation by improving
solubility and absorption-enhancement technique.
ii. Hard Gelatin-Capsules: Most of the pharmaceutical
capsule products are hard gelatin capsules. These are
made out of two shells: one is capsule body and the
shorter one is called the cap. The normal Hard gelatin
capsule shells are made from mixtures of gelatin, sugar,
and water. These gelatins are clear colorless and most
importantly tasteless.
iii. HPMC Capsules: Hydroxypropyl Methyl cellulose Is
a water soluble nonionic cellulosic polymer that is used
to form non-gelatin capsules with assured better patient
compliance. So technically the shell substance
formulated like so that the substance acts like a gelatin
substance.
iv. PVA Capsules: Following the description stated in
International Patient application WO 9 755 3723
polyvinyl alcohol (PVA) and optionally use of some
supporting materials all being film-forming polymers
[17]
 lacks a vital part like gelling properties that are
important for soft capsule production to be used in
rotatory die process. Hence the establishment provides
for the use of pre-made nearly water free plastic roll
films which may be given to a fed of rotatory die
encapsulation unit for soft capsule production.
v. Starch Capsules: It is formulated by using normal
plasticizers such as sorbitol, glycerol, etc. and water is
used to form a molten mass, later on the water can be
extruded to set within less than 20 seconds resulting
production of mechanically strong, elastic film. To
produce such capsules the fusion process is used. This
process is comparable to the soft gelatin capsules.

o Manufacturing of Capsules
Looking at the types of capsules we can safely assume that
the manufacturing process are made around the soft gelatin
and hard gelatin capsule production moto. Other types of
capsules are formulated as so that the capsules can be made
in same industrial machineries which are used in
manufacturing in hard and soft gelatin capsules. The standard
procedure of those two processes are described underneath.
i. Hard gelatin-capsule formulation: In the case of Hard-
Gelatin capsules the capsules are fabricated and
supplied empty to the pharmaceutical manufacturers
and then filled in a separate operation. Manufacturing
gelatin capsules involves a sequential process that
requires strict quality control. Hard Gelatin capsules are

[18]
 made by the dip-coating method and the various stages
are as follows:
Stage 1: Preparation of the gelatin solution A.K.A dipping
solution:
The dipping solution actually is a gelatin and demineralized
water mixture prepared by heating it to 60-70℃ in jacketed
pressure vessels. This solution contains 30 to 40% of gelatin
and it makes it highly viscus. Air entrapment is a problem in
this stage which effects the yield of capsules, inconsistent
yield of capsule weight. To remove such problem vacuum is
applied to the solution; the time duration of this process
depends of batch size.

Fig.7. Hard gelatin capsule manufacturing

Following the above steps, coloring agents are added to
attain desired final capsule appearance. At this stage some
other processing aids may be added. E.g. sodium lauryl

[19]
sulfate as surface tension reducer. The viscosity is measured
and controlled by addition of demineralized water if needed.
Stage 2: Dip-coating the gelatin solution on to metal pins
(molds)
Capsule shells are made in strict climatic condition by dipping
pairs of standardized steel pins arranged in metal bar rows,
dipping into the water-gelatin solution 25-30% w/w at 50℃
in a jacked heating pan. The molds consisting lower
temperature the gelatin begins to form a thin film on the
molds.
The pin rows are arranged so that the bodies and caps are
formed side by side simultaneously on the opposite side of
the machine.

Stage 3: Rotation of the dip-coated pins

Following the dipping process of the gelatin solution is stuck
on to the surface of the pins. The bar with the pins are then
removed and rotated several times to evenly distribute the
solution on the pin, correct gelatin distribution is a vital
aspect of drug release so the thickness and strength should
be uniform.
Stage 4: Drying of the gelatin-coated pins
After satisfactory amount of rotations are done to achieve
the even distribution of the solution the pin head are dried
with a dry cool wind on pin heads.
Stage 5: Stripping and trimming
[20]
After the drying process the extra un even opening of the
capsule body or caps are stripped using a bronze jaw to attain
proper length of the body or caps.
Stage 6: Joining of the trimmed capsule shell
After the trimming the trimmed extras are recycled and the
two halves are joined together to the pre-closed position
using a pre-lock mechanism. Next step is printing if needed
before packing or shipping.
Stage 7: Printing
After the capsule shells
are formed the rotatory
printer can print branding
or identification
characteristics on the
capsule in a very fast way.
Printing reduces the
product confusion to the
consumers and handlers Fig.8. Rotatory capsule Printer
both.
Filling of the hard gelatin capsules
The filling of hard-capsules is an established technology, the
equipments can range from small scale manual filling
(example: Feton capsule filling machine) through
intermediate-scale semi-automatic to large scale fully
automatic machines. The Hard capsules also can be hand
filled just like it happened in the old days of compounding
pharmacy. The main difference of the various filling
[21]
procedures is based on the way the filling material is weight
during the filling. Some basic steps in filling hard gelatin
capsules are described here.
– Capsules are rectified (empty gelatin capsules are placed
on the removable plate with downward facing bodies)
– Caps are then separated from the bodies.
– Dose is then filled in the body using a spatula in manual
process or automatically using weighting hold and
individual dose distributer.
– Then the replacement of caps or the replacement of
capsule shells are used to close the capsules.
– Then the filled capsules are ejected.
Filling of semisolid or liquid formulation into hard gelatin
capsules are quite different. As drug discovery continues to
produce lesser soluble molecules in water, there is a growing
need to construct techniques which can improve drug
solubility. One such method is the use of liquid-based
formulations containing lipids, solvents, or surfactants,
usually in combination, to improve the solubility of the drug
as well bioavailability. The final construction may be
completed by using piston pumps in solid gelatin capsules as
a room temperature liquid, or as a molten semisolid.
Liquid filling or semi-solid composition depends on the
viscoelastic properties of composition and the need to
complete certain features at filling temperatures. As a
general rule, the construction should have a viscosity
between 50 and no 1000 Centipoise (cP) (although more is

[22]
done high viscosity may be suitable for production) and
should not exceed 70 °C.
Lipophilic Vegetable oils e.g., Castor oil, Peanut oil,
excipients Olive Oil, Fractionated coconut oil, Sesame oil,
Corn oil, Hydrogenated vegetable oil, soybean
oil
Esters e.g., Glycol Stearate, Glycerol Stearate,
Ethyl oleate, Isopropyl myristate.
Fatty Acids e.g., Stearic acid, Palmitic acid,
Laurie acid, Oleic acid
Fatty Alcohols e.g., Stearyl-alcohol, Cetyl-
alcohol.
Hydrophilic PEG 3000-6000 MW
excipients
Amphiphili PEG esters (e.g., Gelucir 44/14;50/30 Labrafil),
c excipients Poloxamers, Lecithin
Abbreviations: PEG = Polyethylene glycol; MW = Molecular weight
Table.2. Liquid Excipients Compatible with Hard Gelatin capsule Shells

Locking and sealing of hard gelatin capsules: Hand filled

capsules are locked and sealed to prevent the detachment of
caps from the bodies during packaging, storing, or
transporting. The locking and sealing prevent capsule content
exudation. Different manufacturers adopt different locking
and sealing methods which includes.
– Banding method
– Spot welding method
– Moistening method
– Spot welding method
[23]
– Thermal welding method
– Using coni-snap capsules
ii. Soft Gelatin capsule formulation: Many problems that
comes with tableting, including poor compaction and
lack f content uniformity or irregular weight uniformity
can be reduced to zero when a drug is made as a soft
gelatin capsule. Also, highly susceptible to oxidation
agents can attain its stability through gelatin
capsulation.
Vehicles used in soft gelatin capsules: These are prepared
to contain many kinds of liquids, pastes, and dry fills. So,
encapsulable gelatin capsules include the following kinds
of liquids:
– Non-volatile and water immiscible volatile liquids like
vegetable and aromatic oils, chlorinated hydrocarbons,
aromatic and aliphatic hydrocarbons, esters, ethers,
alcohols, and organic acids.
– Non-volatile water-miscible liquids, like polyethylene
glycols and nonionic surface-active agents, e.g.
polysorbate 80.
– Water-miscible and relatively non-volatile substances
such as isopropyl alcohol and propylene glycol
depending on factors such as concentration used.
Manufacturing processes of soft-gelatin Capsules:
i. Plate process: This is the oldest process of
manufacturing soft gelatin capsules in pharma
commercial industry. In this process a plasticized gelatin
is placed over a die plate having a number of pockets or
[24]
 molds. By applying vacuum, the sheet is drawn into
these pockets and forms capsule walls. Then the capsule
wells are filled with filling agent or medication-liquid. A
second sheet of gelatin is placed on the filled capsule
and pressure is given to seal the molds. The final stage is
cutting the capsules separate. It is a method to be used
in small scale production of soft gelatin capsules.
Specialty of such capsule is it has one side flat.

ii. Rotary Die Process: In this manufacturing process the

problems like the ununiformity and lower standards of
accuracy is eliminated which plagued the Plate process.
Here, two Rotatory die made plasticized gelatin ribbons
are continuously fed with the liquid or semi solid or the
paste to be filled between the rollers of the rotary die
mechanism. The feed material is force injected between
the two ribbons. Which results swelling in the left- and
right-hand die pockets which govern the size and shape
of the soft-gels as they converge. In the process the die
pockets are hermetically seals and cuts out the filled
capsule in the same machinery.

iii. Reciprocating Die Process (Norton Capsule

Machine): This process was developed by Norton
Company in 1949. Having a similar process in the
ribbons part just like the rotatory process it differs in the
actual encapsulating process. Here the gelatin ribbons
are fed between a set of vertical molds which
continually opens and closes in the pocket rows in
[25]
 gelatin ribbons. These pockets are filled with the
medicinal component which is needed to be filled and
then they are sealed and cut in the same machinery
process. The Fresh cut capsules from the ribbons fall
into a cooled solvent bath which prevents the capsule
from adhering to each other.

iv.Accogel Process: This process is prepared by Laderle

laboratories in 1949 to encapsulate powders and
granules in soft gelatin capsules.
Its rotatory process involves a measuring roll, a die roll,
and a sealing roll. The measuring roll and the die roll
pockets are directly aligned with each other. The
granular filling material is kept in the pocket using the
measurement of roll under vacuum. A plasticized sheet
is sucked into the die pockets of the die rolls, As the
measuring roll & die roll rotate, the measured doses are
shifted to gelatin-lined pockets of the die roll. The
rotation continues and the filled die converges with the
rotating rolls that is incorporated with the sealing, there
second gelatin sheet is applied to form the other 50%
part of the capsule. The pressure between the die roll
and the sealing roll develops such forces that can cut
out the capsules.

v. Seamless process (Bubble Method): In this process no

dies are used. This process is also known as a bubble
method that creates neat, spherical soft gelatin capsules
called and they are termed ‘pearls’. In production the
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 molten gelatin stream flows through the outer outlet of
a concentric tube at a stable rate, and the filling or the
medicated liquid is filled through the inner orifice with
the help of a precision metering pump.
Quality control tests for capsules: Various things are
checked during the capsule formation’s qc department
during the encapsulation of the soft gelatin capsules like
the gel ribbon thickness, soft-gels seal thickness, Weight of
the capsule shell and its variation from capsule to capsule,
Moisture level of the capsule shell, and other related
parameters.
Finished product quality control tests are consisted of:
– Weight variation tests
– Uniformity of content
– Disintegration time test for capsules
– Dissolution test for capsules
– Moisture content
– Moisture permeation test
– Microbial content test
– Shelf-life test
– Stability testing of capsules
Packaging and storage of Hard Gelatin capsules: These kinds
of capsule’s moisture content remain around 13% to 16%. If
we lower that shells become brittle and may show cracks,
and if we store or keep them at higher moisture content
place then the gelatin structure may lose shape and
deformity may occur. Similarly, it is important to maintain

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relative humidity of 40% to 60%. Similar deformities can be
seen when we put them in inadequate conditions.
Packaging and storage of Soft Gelatin capsules: These kinds
of capsules are more dynamic than hard gelatin capsules.
because these capsules are soft due to plasticizers residual
moisture. Volatile components of the encapsulated drug can
evaporate into the atmosphere so precautions should be
taken to ensure capsules are not cracked open during storage
or transportation. empty capsule shells are stored in 15℃ to
25℃ with relative humidity between 35-65%. These
conditions the capsules to minimize moisture absorption
or loss. Also prevents the physical changes in dimensions
during the manufacturing procedure.

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