CONTENTS:

INTRODUCTION

PLANT LAYOUT

EQUIPMENTS

VALIDATION

DOCUMENTATION

QUALITY CONTROL TEST

RECENT RESEARCHES

REFERENCES

TABLETS
I. INTRODUCTION
a) Definition: - These are solid dosage forms each containing a unit dose of one or more
medicaments.
b) Advantages: -

Unit dosage form with greatest dose precision & least content variability among all oral dosage
forms dosage form
Cost is lowest among all oral dosage forms.
Lightest & most compact of all oral dosage forms.
Easiest & cheapest to pack & ship among all oral dosage form.
Tamperproof.
May provide greatest ease of swallowing with least tendency for hang up above the stomach.
Better suited for large scale production
Possesses best combined prop. Of chemical, mechanical, & microbiological stability of all oral
dosage form.
c) Disadvantages: ( why we have to go for dosage form other than TABLET)
Some drugs can not be compressed into tablets.
Drug having amorphous nature & low density drug can not compressed into tablets.
Drugs with poor wetting slow dissolution properties, immediate to large dosages, optimum
absorption high in GIT or any combination of these features may be impossible to formulate & make
as tablet.
Bitter tasting drugs, drugs with an objectionable odor, drug sensitive to oxygen coating may be
required.
TYPES OF TABLETS:ORAL TABLETS FOR INGESTION

Compressed tablets

Multiple compressed tablets (Layer & Compression coated)

Repeat action tablets

Delayed action & enteric coated tablets.

Sugar & Chocolate coated tablets.

Film coated tablets

Chewable tablets.

Mucoadhesive tablets.
TABLETS USED IN ORAL CAVITY.

Buccal tablets.

Sublingual tablets.

Troches& lozenges.

Dental cones.

TABLETS ADMINISTERED BY OTHER ROUTES.

Implantation
Vaginal tablets.

TABLET USED TO PREPARE SOLUTIONS.

Effervescent tablets.
Hypodermic tablets
Tablet triturates
Dispensing tablets

VARIOUS EQUIPMENTS USED :Equipment for the manufacture of pills compressed tablets and hypodermic tablets.
For effective operation the tablet production department shall be divided into three district and
separate sections:
a. Granulating section.
b. Tableting section.
c. Coating section.
The following equipment is recommended in each of the three sections:
a. Granulating section
1. Disintegrator.
2. Sifting
3. Granulator.
4. Dryer
5. Mill( for reduction in particle size of granulating mass)
6. Blender
7. Powder Mixer.
8. Mass Mixer.
9. Granulator.
10. Ovens, thermostatically controlled or other suitable equipment.
b. Tableting section.
1. Tablets machine single punch or rotary
2. Pill machine.
3. Punch and dies storage cabinet.
4. Tablet counter.
5. Metal detector.
6. Tablet deduster
7. In-process testing equipment like hardness tester, accurate weighing balance and
disintegration test apparatus, friabilator, dissolution apparatus.
The tableting section shall be free from dust and floating particles. For this purpose it is
desirable that each tablet machine is connected to an exhaust system and isolated into cubicles.
c. Coating Section:
1. Jacketed kettle, steam gas or electrically heated for preparing solution.
2. Coating pan.
3. Polishing pan.

4. Heater and Exhaust system.

5. Air conditioning and Dehumidification Arrangement.
The Coating section shall be made dust free and suitable exhaust provided to remove excess powder
and the fumes resulting form solvent evaporation. An area of minimum thirty square meters for each
of the above three sections is recommended for basic installations.
The manufacturing of Hypodermic Tablets shall be conducted under aseptic conditions in a separate
air-conditioned room, the walls of which shall be smooth and washable. The granulation, tabletting
and packing shall be done in this room.
III. BUILDING & FACILITIES:
Designed according to GMP practices which ensures .

Prevention of cross contamination

Proper air handling systems.
Proper cleaning & sanitary facilities.
Proper Lighting
Proper Plumbing
Proper washing etc.

LAYOUT OF TABLET DEPARTMENT:

It is the organized properly planned
arrangements.

INTERDEPARTMENT and INTRADEPARTMENT

PROPER LAYOUT:
Increases productivity
Helps in proper utilization of
MAN ( Remembered 4 M)
MATERIAL
MONEY
MACHINES

AREA REQUIREMENT:
Tablets
Uncoated tablets

Basic installatio
( sq. mt)
30

Ancillary area requirement(

sq. mt)
10

Coated tablets

60

20

ENVIRONMENT REQUIREMENT:
Name of area
WARE HOUSE
WEIGHING AREA
TABLETTING AREA
CENTRAL CORRIDOR
Temperature 2550C
Humidity 55 10 % RH

Pressure maintained
10 PASCAL
20 PASCAL
15 PASCALS
30 PASCALS

Humidity should be lowered for specific products like Effervescent tablets & moisture sensitive
drugs.
Pressure within areas like mixing & tabletting area should remain on negative side than central
corridor so that any dust or powder material does not contaminate the central corridor or other
department.
All areas should be free from dust & floating particles, if possible air conditioned.
In coating section suitable exhaust systems to remove excess powder & fumes from solvent
evaporation.
There should be properly organized & working air handling system containing prefilters,
particulate matter air filters to supply purified air.
Temp control & Air control should be such that there should be comfortable working
environment. & no impact on characteristics of in process materials such as granulations, raw
materials.
All areas should be properly ventilated with the use of roof fan.
QUALITATIVE LAYOUT WITH CIRCULAR FLOW:

Circular layout
Materials are weighed into batch quantities in dispensing & then moved into the manufacturing
area. After completion of manufacturing the finished tablets are placed in quarantine & moved to
bulk stock upon release .when packaging run is scheduled tablets, packaging components, are
delivered from the bulk stock & approved storage area.

LAYOUT WITH CROSS OVER TRAFFIC:

Advantage- space conservation,

Disadvantage:-Crossover traffic pattern may lead to contamination & mixing.
LAYOUT WITH PARALLEL FLOW :-

Advantage :- Minimum contamination or mix up.

Disadvantage :- Additional space required.

Layout with different Floor system

(A)

High Rise Tower System Incorporating Warehouse,utilities,Administration

(B)

Three floor system using automatic guided vehicles to aid material flow

This is designed to maximize the use of pneumatic or vacuum transfer systems and is intended
to be a totally enclosed dedicated system.There would be an option within product to operate
the plant on the campaign basis.

(C)

Single floor with material flow aided by vacuum or pneumatic system

This is the LHOEST concept; the pneumatic transfer systems have been replaced by an
AGV/IBC mechanical handling system.

 The Lhoest concepts

In our opinion, one of the best ways to approach plant design is by implementing the concepts known
in the professional literature as Lhoest Concepts. These internationally recognized concepts have been
experienced, evaluated and improved since their inception. They are presently defined as the
synergistic implementation of nine basic individual concepts, combined in a way that optimizes
production conditions and maximizes flexibility, GMPs and cost efficiency.2,3
The Lhoest concepts have been the basis for dozens of pharmaceutical manufacturing plants currently
in use throughout the world. The first one was built in the 1980s in Spain and the most recent one, the
Kowa plant in Nagoya (Japan) has just been nominated among the five finalists of the international
competition for the 'Facility of the Year 2005' organized by the International Society for
Pharmaceutical Engineering.4,5
These pharmaceutical facilities have been approved by all authorities and have been successfully
implemented in Belgium, Croatia, France, Germany, Holland, Italy, Japan, Norway, Puerto Rico,
USA, Slovenia and Spain.
The Lhoest concepts focus on nine specific areas:
1. Room segregation. One of the main concepts is the full segregation between clean production
areas and technical areas (or optically clean areas), which means the relocation in technical
areas of all material and pieces of equipment that are not absolutely needed in the production
rooms (Figure 4). These include

The materials feeding the process machines and intermediate bulk products that are stored in
specially designed, tight stainless steel IBCs that are only handled in technical areas.

Sources and distributions of energies.

Pumps, gas cylinders, electrical motors, electrical boards, hydraulic drives and in general any
component or machine part not absolutely required in the production rooms.

The installation 'through the wall' of production equipment is always recommended.

2. Containment. The transfer of products to and from IBCs has to take place under fully contained
conditions. This not only renders the plants a lot cleaner but mainly avoids cross-contamination
and any exposure of operators to active dust at any time. A key element is the connection

system, usually called 'docking station', that may not allow the release of any trace of product at
any time (during phases of connection, disconnection, standby, or during cleaning and
inspection).6
The absence of any powder release applies to clean rooms as well as technical areas. Although a lot
of suppliers propose connecting stations, very few connecting stations comply with containment
according to Smepac rules.7 Connecting stations that do comply with Smepac have been tested
successfully in Japan.8
The rule of containment should be applied throughout the whole production process.
3. Gravity transfer of goods. The transfer of goods, powders, granules, finished tablets, capsules,
etc. by gravity is by far the simplest, safest and most economical one. For this purpose, the
production floor is located between two technical floors
The advantages resulting from the combination of the first three concepts are important from an
economic and GMP perspective, namely:

Significantly less ground space is needed because the plant is on three levels, sometimes five
or more.

Technical areas representing 6080% of the total building volume can be constructed at about
half the unit cost of clean areas (in a conventional plant, clean areas can, conversely,
represent 80% of the total plant volume).

The more compact construction allows shorter connections for all air and energy supplies.
Additionally, because these distributions are located in technical areas, their unit installation
cost is also reduced.

Highly improved GMPs result from smaller and significantly simpler production rooms
combined with full containment and elimination of IBCs and trucks from the clean areas.

4. Islands of automation. In this concept, every individual production machine is located in a

small clean room totally independent of the other islands. It possesses its independent air
handling system, its own supplies and is able to run on its own at the optimum speed, just as a
small independent production plant (Figures 67). The advantages are:

Maximized flexibility products can be transferred from one island to any other island in
the factory. Changes in manufacturing processes or in delivery requirements have no impact
on the plant Itself.

A machine breakdown has minimum influence the operation can be easily and rapidly
deviated to another island. Maintenance is able to operate without any disruption of
production.

New pieces of equipment can be installed in spare rooms without influencing the system

Every machine operates at its maximum speed.

Automation allows some machines to run day and night, unattended.

It must be emphasized that applying these first four concepts permits the design of OSF facilities
where different GMP classes of medicines (highly actives, antibiotics, etc.) are manufactured at the
same time. Such plants have been approved by FDA. Islands of automation operate best in
conjunction with the next five concepts.
5. Automation of material handling. The automated transportation of materials (powders,
granules, tablets, capsules, pellets) to and from islands of production is cost effective. The
automation approach must be adapted to the project and obviously manual transportation can
also be used in countries with low labour costs. All containers are standardized and equipped
with patented connection devices to guarantee total containment and automatic, dust-free transfer
under the most stringent conditions to agree with the new Smepac rules. Depending on the case,
the automated transportation is achieved by automated guided vehicles (AGVs, Figure 8),
monorails, shuttles or elvecars (Figure 9). The experience has shown that in elevated labour-cost
countries, this automation is always justified. The advantages provided by automated materials
handling are:

Experience shows that in a conventionnal plant, people use up to 40% of their time carrying
or moving material around the plant. This time is fully recovered with automated
transportation.

The system operates unattended, 24 hours-a-day and 7 days-a-week, with resulting increase in
plant capacity and efficiency.

The materials handling is entirely located inside technical areas: clean rooms and clean
corridors are no longer contaminated by the cumbersome handling of materials and can be
built significantly smaller.

6. Computer integration. With their impressive memory and their high level of repeatability,
Computerized systems are an enormous help in tasks like management of inventories, storage of
procedures, and specifications and assistance to manufacturing.
7. Warehouse integration. Considerable advantages result from the integration of the warehouse
in the bulk production facilities:

Exchanges of products between warehouse and production are implemented within seconds.

Intermediary staging areas are eliminated with corresponding savings in manpower, surface
area and paperwork.

The inventory of the warehouse is updated automatically and in real-time.

If the warehouse is constructed as the core of the production building, additional structure and
isolation savings are produced.

8. Cleaning-in-place of machines, containers and installations. This concept is well known. It is

applied whenever justified.
9. Segregation of circulations. Fully segregated circulations are provided for the categories of the
people and materials shown in Table 1 that are practically always present in any OSF plant. It is
an essential, under the Lhoest concepts, to ensure that no cross-contamination can possibly occur
through the circulation of different classes of people or materials. In other words, dedicated
changing rooms, provided for each category of personnel, lead through dedicated corridors,
directly to the rooms authorized to that particular category, and without any possible interference
from other classes. The same applies to materials. This objective is not easy to achieve, but the
best OSF plants in operation today are based on
(D) High rise tower using gravity to aid material flow

 This building has four upper floors and a ground floor designed to maximize the use of gravity
in feeding powders and product starting from dispensary to finishing in packaging area.

QUANTITATIVE LAYOUT: SUPPOSE A BATCH OF 1,00,000 TABLET IS TO BE PREPARED

EACH TAB WEIGHING 600mg THEN TOTAL POWDER MATERIAL TO BE TAKEN
WILL BE 60Kg.
EQUIPMENTS USED WILL BE OF FOLLOWING
CAPACITY:A. PLANETARY MIXER 100Kg
B. FLUIDISED BED DRYER 60Kg
C. FOR FINAL MIXING OCTAGONAL MIXER 500Kg.
D. RMG 60Kg
E. FBG 60Kg
F.COMPRESSION MACHINE 42 PRODUCES 1 LAKH TABLET IN 1 HOUR..
G. COATING 16 INCH PAN SIZE CAN COAT 50,000 TABS AT A TIME
H. PACKING-STRIP & BLISTER(single track) CAN PACK 3 LAC TAB. PER DAY
WIDTH USED IS 150nm..

Granulation:
Wet Granulation
Direct Compression
Dry Granulation
Slugging
Roll Compaction

Dry granulation
Dry granulation is used when
Effective dose of drug is too high for direct compression
Drug is sensitive to heat or moisture or both.

The most commonly used equipment for dry granulation is Roller compactor
Roller compactor:
It utilizes two rollers that revolve towards each other.
Powdered material is fed between the rollers by a screw conveyor system
After passing through the rollers , compacted mass resembles a thin wide ribbon that has fallen
apart into large segments.
Compaction force of roller compactor is controlled by 3 variables.
The hydraulic pressure exerted on compaction rolls.
The rotational speed of the compactor rolls.
Rotational speed of feed screws.
o IPQC is done to test compaction uniformity & machine capacity

Advantages of Roller compaction

Disadvantages of Roller compaction

b) WET GRANULATION: The ideal equipment for the preparation of granulation by wet granulation process would be one unit
which is capable of sequentially dry mixing, wet massing, agglomerating, drying& sizing of the
material being processed
PROCEDURE FOR WET GRANULATION

Wet granulation manufacturing steps:

1. Sifting
2. Granule formation
3. Drying
4. Milling
5. Blending
MIXING EQUIPMENTS:
Mixing process is done before and after granulation
Selection of the proper mixer for the process depends upon quality of material, material
bed etc.,
Various mixer used here are like
Ribbon Mixer
Planetary Mixer
Twin Shell (V-shaped)
Double Cone Mixer
Tumbler Mixer
Sigma Blade Mixer
These equipments are also used in the powder MIXING.
WET GRANULATION:

Classification of Equipments:A) High shear mixer / granulator:- includes

Littleford lodige mixer
Littleford MGT Granulator
Gral mixer /Granulator
Diosna mixer / Granulator
B) Granulator with Dryer :- Includes
Fludised bed Granulator
Day Nauta Mixer Processor
Double Core/ Twin Shell Granulator
Topo Granulator
C) Specialized Granulators :- Includes
Roto Granulator
Marumerizer
D) Use for both Wet/Dry Granulation: Oscillating granulator
ZL rotary granulator
Most commonly used granulator:
o Rapid mixture granulator(RMG)
It utilizes a bowl (1) mounted in the vertical position.
A high speed mixer blade (2) revolves around the bottom of the bowl.
It also contains high speed chopper blade (3) which functions as a lump & agglomerate breaker.
A pneumatic discharge port (4) provides the unit with automatic discharge.
The lid has three openings a) spray nozzle b) air exhaust sleeve c) viewing port.
Typical time sequences - mixing-2 min or less, granulating - 8 min or less, discharge - 1 min

Advantages - Produces granulation with more normal particle size distribution with less fines
also more spherical granules are produced.

Diosna mixer/ granulator

Diosna mixer/ granulator
Another type of high speed powder mixer and processor
The mixer utilizes mounted in vertical position.
A high speed mixer blade rotates around the bottom of the bowl. The blade fits over the pin bar
at the bottom of the mixing bowl which powers the blade. The mixer also contains chopper
blade which acts as a lump and agglomerate breaker. The pneumatic discharge port provides
the unit with the automatic discharge. The unit is provided with a lid.
Little ford MGT
In this the horizontal position of lodige is rotated 90 degree to vertical configuration of Lodige
unit, the drum has been converted to bowl and the discharge port is provided for facilitate
emptying.
The principle of the operation is as same as for Diosona mixer.
Gral mixer
It is the modification of the industrial planetary mixer. The difference between Gral and
planetary is that new unit has two mixing device. A large mixing arm is shaped to the rounded
configuration of the bowl and provides the large scale mixing motion on the powder. A smaller
chopper blade enters off-center from the mixing arm and is located above it. The bowl may be
loaded at floor level and then raised to the mixing position by hydraulic elevator cradle

Gral mixer
o FLUID BED SPRAY GRANULATORS:-

 The air flow necessary for fluidization of powders is generated by a suction fan mounted in the
top portion.
The air used for fluidization is heated to the desired temp by an air heater.
The liquid granulating agent is pumped from its container & sprayed as a fine mist through a
spray head onto the fluidized powder.
The wetted particles undergo agglomeration through particle particle contacts.After appropriate
agglomeration is achieved ,the spray operation is discontinued& the material is dried ,discharged
from unit.
Advantage- a) Rapid wet massing, agglomeration & drying within one unit
b) 60-90 min or less is completion time.
c) 2-6 times greater heat transfer than tray dryer
d) Uniform drying, prevents migration of dye or drug.
e) Effective utilization of time, space, personnel,& energy.
Disadvantage: - Demixing, (occurs when there is difference in particle size/ density.)
- Filter clogging.
- Electrostatic charge development
- Solvent explosion
Designs - a) Top spray
b) Rotary disk
c) Bottom spray (WURSTER PROCESS)
Three methods of drying options available by Day Nauta equipment
a) hot air
b) Direct heat application to the shell
c) vacuum application
Advantages: Capable of producing uniform powder mixers
which do not demix
Flexible drying options vacuum or hot air.
Excellent product temp control & uniformity.
Ability to mix, granulate, dry & package from
one machine.
Freedom from product caking & lumping.
Low operation & maintenance cost
o Little ford lodige mixer
The first high shear mixer
With some formulation it can also produce agglomerated granules that are ready for fluid bed
The unit consists of a horizontal cylindrical sheer equipped with a series of plough shaped
mixing equipments and one or more high-speed blending chopper blades operating during
operation
Spray nozzles are provided for addition of the liquid above the chopper blade
In the operation the plough shaped mixing tools are rotated at variable speed to maintain the
material in the fluidized conditions
Liquid enters through the nozzles above the chopper so it will get immediately dispersed
Complete mixing may be obtained in as little as 30 to 60 seconds
This is most often used for wet granulation.

Little ford lodige mixer

Day Nauta Mixer
It is vertical screw mixer. A screw assembly is mounted in a conical chamber, with the screw
lifting the powder to be blended from bottom to top. The screw assembly rotates around the
conical chamber wall to ensure more uniform mixing.
Marumerizer

(Extruders)
Moist granules, from an extruder or mixer, are fed into the spinning friction plate and thrown
against the inside of the Marumerizer, forming a twisting rope. Collisions of the particles with the
wall, friction plate, and other particles result in plastic deformation of the granules, forming spheres.
The final shape of particles is time and formulation dependent. Once the desired particle shape is
achieved, the batch is discharged through a manual plug valve and discharge chute, collected, and
dried.
The Marumerizer is used for a number of reasons:
Wet cutting device: The extrudate falls into the Marumerizer and is cut into segments of almost
equal length
To round the edges: The cylindrical extrudate stays in the Marumerizer for a short period of
time to round the edges. This helps to avoid the creation of dust during transport and handling
To make spheres: Also known as spheronization, this is the time period for the extrudate to stay
in the Marumerizer until spheres are formed. This can be useful for coating or aesthetic
purposes
The Marumerizer provides a very narrow particle size distribution improving product yield
It increases the bulk density of the extruded material up to 25%
After spheronization in the Marumerizer the flowability of the product is significantly
increased, thus preventing sticking and bridging problems.

(Marumerizer)
Spheronizers.
Spheroidizers are used to extrude raw material or particles into pellets. This equipment is being used
byspheroidizer pharmaceutical industry to manufacture various size pellets. The process involves
agglomeration of active pharmaceutical ingredients and forming them into spherically shaped beads
also known as pellets.
A wet mixture of active pharmaceutical ingredients is extruded, broken down and rounded in a
spheronizer. Spheroidizers are also referred to as spheronizers. This type of machine provides a
spherical product that is more higher performing and attractive final granular product form than
unspheronized. Pharmaceutical spheronizers are available with varied capacities.
Uses of Spheroidizers
They are used to do the following:

Fines generation
Limit dusting
Densify the surface for stability
Produce granule with a smooth surface
Reduce coating material necessary
Increase bulk density
Increase flowability

Melt Granulation/Thermoplastic Granulation

In agglomeration by the DISTRIBUTION mode, a distribution of molten binding liquid on

the surfaces of primary particles will occur, and agglomerates are formed via coalescence
between the wetted nuclei.
In agglomeration by the IMMERSION mode, nuclei are formed by immersion of the primary
particles onto the surface of a droplet of molten binding liquid
The distribution of molten binding liquid to surfaces of nuclei has to be effected by
densification prior to coalescence between the nuclei.
The distribution will be a dominant mode when the molten binding liquid droplets are smaller
than the solid particles or of a similar size & by a low molten binding liquid viscosity.

 On the other hand, the immersion mode will dominate when the molten binding liquid
droplets are larger than the solid particles and when molten binding liquid of high viscosity,
which could resist breakup by dispersive forces.
e.g. Diltiazem HCl, Diclofenac
DRYING OPERATIONS:Instrument used for drying are known as DRYER .
1) FLUIDISED BED DRYER :Principle ;-When a gas is allowed to flow through a bed of particulate solids at a velocity greater
than the settling velocity of the particles.& less than the velocity for pneumatic conveyor, the solids
are buoyed up & become partially suspended in the gas stream.the resultant mixer of solids & gas
behaves like a liquid & solids are said to be fluidized.
HORIZONTAL FLUIDISED BED DRYER
VERTICAL FLUIDISED BED DRYER
Dryer capacities range from 5kg to 200kg.avg. drying time is about 20-40 min.
Advantages:2-6 fold advantage in thermal efficiency over tray dryer.
Faster in both drying & handling time than the tray dryer.
No hot spot
Higher drying temp can be applied than tray & truck.
1) FLASH DRYER.
In this the moistened drug mass is suspended in a finely divided state in a high velocity (3000 t0
6000 ft/min) high temp (3000f-13000f) air stream.
The dispersed particles may be carried in the air stream to an impact mill,or pneumatic flow itself
may reduce the particle size of friable material.The resultant attrition exposes new surfaces to for
more rapid drying.
This drying is referred as flash dryer because drying time is extremely short & drying air temp
drops from 13000F to 6000Fin two seconds & 3500F in 4 seconds.
2)Tray dryer:
In this trays are arranged in cabinet and air is circulated over it
Drying time depends on
Temperature of heated air
Depth of bed
Circulation of heated air
Distance between trays
b) Granulator: (S.O.P. OF Granulator)
1. Make sure that Granulator is cleaned and dried.
2. Check necessary arrangement and power supply of Granulator.
3. Switch on the Granulator and see weather it is rotating properly or not.
4. If any disturbances found then switch off and make proper arrangement.
5. Now switch on the vacuum pump for transfer of powder from vessels to Granulator.
6. Slowly add formed binding solution to Granulator with proper care as it may raise dust
contamination.
7. As soon as all powder and binding solution is filled close the opening door.

8. Make sure that no lickage or space is left, so that the cohesive mass will come out of Granulator
at the time of rotation.
9. Switch on Granulator for specified time at a speed I.
10. After time over, stop Granulator, open door and check weather cohesive mass has been formed
or not, else repeat step 9 again.
11. As soon as mass has been formed close the door and start Granulator to granulate the mass at
speed II with help of chopper blade.
12. After time over, stop Granulator, open the bottom door and transfer the formed granules for
further process.
13. Make sure that before leaving Granulator for further batch, it should be cleaned and dried.
14. Attach a necessary sticker card of cleaned and dried on it with date and signature of
superintendent.
Compression machine:
Tablet machine is regulated by..
Number of tooling sets
Number of compression station
Rotational speed of the press

Rotary tablet press (top view)

Tablet compression cycle

Different stages of compression:

Feeding

Filling

Compression

Ejection

Tablet

S.O.P. OF COMPRESSION MACHINE:-

1. Make sure that Compression Machine is cleaned and free

from granules of previous batch.
2. Check necessary arrangement like placement of hopper, feed
frame, cam tracks arrangement, die cavity, arrangement of
lower and upper punch, ejection level, scrapper arrangement.
3. Adjust the weight of tablet by weight adjustment knob.
4. Switch on the Compression Machine and see weather it is
rotating properly or not.
5. If any disturbances found then switch off and make proper
arrangement.

e) Packing machine:

(S.O.P. OF PACKING MACHINE)

PACKING CAN BE DONE EITHER USING BLISTER OR STRIP PACKAGING MACHINE.
1. Make sure that Packing Machine is cleaned and free from tablets/capsule of previous batch.
2. Check necessary arrangement like placement of aluminum foil, spiral hopper, sealing temperature
at two rollers, die cavity cutting jaws.
3. See weather vacuum is working properly or not.
4. If any problem found then do necessary arrangement.
5. Start Packing Machine and check for necessary arrangement.
6. See weather cutting jaws are working well or not
7. Carry lick test for strip at an interval of 30 min.
8. Operated machine is stopped when batch gets over.
9. Make sure that before leaving Machine for further batch, it should be cleaned properly.
10. Attach a necessary sticker card of cleaned on it with date & signature of superintendent.
DISPOSAL OF REJECTED TABLETS:REJECTED TABLETS ARE DISSOLVED IN WATER AND THAT SOLUTION IS PASSED
THROUGH SEWAGE..
AUXILLARY EQUIPMENTS.

MECHANISED FEEDER

TABLET DEDUSTER

GRANULE LEVEL SENSOR

TABLET COUNTING

TABLET PRINTING

TABLET INSPECTION

1. Tablet Deduster - Tablet dedusters are high technology machines used to clean tablets coming
out of punching machine/press. Tablet dedusting machines clean the tablets off tabletdedusterexcess dust before they are packed.
The tablet dedusting machines clean tablets with the help of a vibratory deduster, which has one of its
ports connected to a suitable suction device. Pharmaceutical dedusters require minimum maintenance
and are easy to clean with easily changeable parts.
Importance
of
Tablet
Deduster
Whenever there is the process of tablet pressing, table deduster is
required. This is because with tablet pressing unwanted powder is
created that adheres to the surface of tablets. The process of tablet
punching leads to formation of edges due to clearance between the
punch and die also known as 'Burrs'. Burrs make the tablets uneven in
size to fit into blister packaging and hinders the proper sealing of
aluminium foil. By removing both the powder and the burrs,
pharmaceutical dedusters enable tablet coating and packaging
machinery to perform as designed.
Types of dedusters

Vertical vibratory: The vertical vibratory deduster uses vibration to move the tablet upward in a
spiral along a smooth, perforated surface. As the machine conveys the tablets, they rub against
one another and shed their burrs. The gentle vibration also loosens and removes dust as the tablets

move up the spiral pathway.The vertical vibratory deduster is the most effective and most popular
for dedusting tablets, also those prone to breakage.
Horizontal vibratory: The horizontal vibratory deduster is similar to the vertical deduster in
operation . Tablets are moved out of the tablet press onto a flat, perforated vibratory bed, which
shakes and vibrates the dust off. Unlike vertical deduster, horizontal units don't convey upward
and thus cannot reach tall bulk bins.
Brush-type: Brush-type tablet dedusters are available in both the configurations, i.e, vertical and
horizontal. The machine uses a motordriven rotary brush that simultaneously conveys and dedusts
the tablets. Brush-type units are effective but are more ideal to handle capsules.

2. Tablet counter
Tablet counters play an important role in the pharmaceutical industry. Tablet counters are ideal
for accurate calculating of all different types of capsules, caplets,tablet-counters tablets, transparent
gel capsules, pills and other similar sized products.
Tablet counters or Pill counters are in use from a very long time. But the accuracy and reliability
of this equipment has continually improved. Today, hundreds of pharmaceutical manufacturers and
laboratories have tablet counting machines running together with their full-scale filling lines. Afer
properly removing excess powder from compressed tablets using tablet dust extractors and de-dusters,
the tablets are counted in the counting machines. Tablet counters ensure 100% accuracy and
pharmaceutical companies have benefited from increased packaging speed, accuracy and peace of
mind.
Types of Tablet Counters
Tablet counters are available as semi-automatic, inline automatic systems, compact counters, high
speed counters. The compact tablet counters are very popular for their accuracy and reliability.
Features of tablet counter
Tablet counters used in the pharmaceutical industry are generally different from those used in
industrial applications. In a medical environment, different quantities of different tablets need to be
counted in succession. For example, a pharmacist may count 40 caplets of a heart patient and then
count 70 tablets of an allergy medication for another patient using the same tablet counting machine.
Therefore, a tablet counter used in pharmaceurtical industry must be able to rapidly count many
different types of tablets. The machine must also ensure that medications of different prescriptions are
not mixed. Clearing the counter before each counting is essential, as it is necessary to reduce the risk
of cross contamination. Pharmaceutical counters should not be bulky. Rather it should be compact and
substantially silent. However there are industrial pharmaceutical tablet counters which are bulky in
size and they use a feed mechanism to transport large quantities of tablets/capsules to a counting
system which counts the tablets.
The process of tablet counting
Tablet counters are equipped with vibratory feeder to align the products for transporting from the
product hopper to the detection unit. Products are scanned and counted with accuracy in the detection
unit. Dust extraction and collection equipment provide an efficient way of removing capsule dust and
other contaminated particles. The counted tablets are then dispensed into a container. Air operated
cylinders in the machine collect and fill the accurate number of products into containers. A specially
designed nozzle helps the chance of product spillage. High technology counters also have process
monitoring sensors and product reject system.
Application of Tablet Counters

Pharmaceutical
Para- pharmaceutical
Medicines

Vitamins
Food-Supplements
Health Products

3. Tablet inspection machine

Tablet checking machines or tablet inspection machines are high precision machines ensuring fast
and accurate checking and sorting of tablet-inspection-machineall defects in different types of tablets.
Certain machines are equipped with automatic cameras, ensure total quality control. Tablet inspection
machines are one of the most widely used pharmaceutical inspection machines. Tablet inspection
machines inspect complete surface of tablets for any visual defects. 360 degree tablets inspection from
rear, front and side surface ensures consistency in tablets. Most inspection equipments are
manufactured according to the GMP standards. These pharmaceutical equipments can inspect up to
200000 tablets per hour depending on the size and shape of tablets and
are easy to clean and maintain.
Types
of
Defects
Inspected
Inspection machines check the tablets for any irregularity in shape, in
terms of length, width, thickness and diameter. The machine has an
automatic rejection system and removes broken, capped, chipped or
incomplete tablets from the conveyor belt. Checks for shade variation,
blurred and scratchy tablets allows for consistency in physical
appearance of tablets manufactured in the same batch. Some of the
defects detected in tablets using tablet inspection machines are:

Size: diameter, length, width, thickness

Shapes: round, oval, oblong, triangular, caplet, pentagonal, octagonal and tear shaped tablets
Integrity : broken, capped, chipped, laminated or incomplete
Aspect : marks, color shade variation
Coating : orange peel, specks, blotches, chips, cracks, picking
Print : incomplete, scratchy, blurred
Embossing : bridging, unreadable, irregular, black speck etc.

Tablet dust extractor

Tablet dust extractors are extremely useful in controlling the dust generated during the compression of
tablets. Pharmaceutical dust extractors are used to remove tablet-dust-extractorexcess powder from
compressed tablets.
Dust extractors not only ensure a dust free end product for use but also health and safety of people
coming in contact with pharmaceutical processing machines. Extracting hazardous dust at the point of
origination and conveying them to the correctly designed filtration system is necessary to protect both
personnel as well as the plant. These machines successfully capture dust with the air stream and
convey it to the dust collector. Dust extraction machines help in removing dust produced from tablet
de-dusting, granulation & other processes. Pharmaceutical dust extraction system avoids product cross
contamination.
Product features
Almost all dust extractors have a stailess steel body with the
following features:

There is a blower fan which is dynamically balanced.

Most machines are fitted with the castor wheels for easy mobility.
Suction capacity varies depending on the size of the machine and the number of tablets required
to be cleaned.
Filteration area is located inside the machine.
The dust extractors have varied dust storage capacities.
There are inlet manifolds and dust collection trays that facilitate to connect any Tablet press
machine and De-burring units.
Can be installed on any tableting machine and de duster.

EQUIPMENTS IN Q.C. LAB.

Hardness tester

Disintegration apparatus

Dissolution apparatus

Weight machine

Friability tester

Single/double beam UV Spectrophotometer

Ph meter

HPLC

Other analytical equipments

EVALUATION OF TABLETS:During & after manufacturing of tablets it is necessary to carryout quantitative & qualitative
evaluation tests to know whether the prepared product is upto the required specifications or not and
take necessary corrective action to minimize deviation from official specifications
This includes IPQC & FINAL QC TESTS.
IN PROCESS QC (IPQC):a) TEST OF GENERAL APPERANCE: - It includes tablets size , shape, colour,presence or
absence of odor,taste, surface texture , physical flaws, consistency & legibility of any identifying
markings.
b) HARDNESS TESTING;- Tablet hardness (Tablet Crushing Strength) is defined as the force
required to break a tablet in a diametric compression test.
Tablets require a certain amount of hardness or strength and resistance to friability to withstand
mechanical shocks of manufacturing, packging,& shipping.
Monosanto tester :-Consists of a barrel containing a compressible spring held between two
plungers .The lower plunger is placed in contact with the tablet & zero reading is taken. The upper
plunger is then forced against a spring by turning a threaded bolt until the tablet fractures. As the
spring is compressed a pointer rides along a gauge in the barrel to indicate the force
Strong cobb tester:-It employs a plunger activated by pumping a lever arm which forces an anvil
against a stationary platform by hydraulic pressure. Force required to fracture the tablet is read from
a hydraulic gauge.

 Pfizer tester :-Works on the principle of a pair of pliers. As pliers handles are squeezed the tablet
is compressed between a holding anvil &a piston connected to a direct force reading gauge.The dial
indicator remains at the reading where the tablet breaks. Extensively used as it is simple, low cost,
Rapid.
Erweka tester :- Tablet is placed on the lower anvil & the anvil is then adjusted so that the tablet
just touches ,the upper test anvil. A suspended weight,motor driven, moves along the rail which
slowly 7 uniformly transmits pressure to the tablet.
Schleunizer tester :- Tester operates in horizontal position. An anvil driven by an electric motor
presses the tablet against a stationary anvil until the tablet breaks..Most widely used as Fast &
Reproducible.
c) FRIABILITY TESTING:- Instrument used is Roche friabilator.
It subjects the tablets to the the combined effects of abrasion & shock.
It is operated at 25 rpm upto 100 revolutions& dropping of tablet done for a distance of 6 inches
with each revolution.
A preweighed tablet is placed in the friabilator & operated for 100 revolutions & reweighed after
dusting.A conventional tablet should be less than 0.5-1% of the weight.
d) WEIGHT VARIATION TEST :This is done by routinely measuring the tablet weight to ensure that a tablet contains the proper
amount of drug.within composite sample that has an acceptable average weight there could tablets
excessively overweight or underweight.

WEIGHT VARIATION TOLERANCES FOR UNCOATED TABLETS

Avg.
Avg. weight of tablet(USP)
Max. % of difference
weight
allowed
of
tablet
(IP)
80 or
130 or less
10
less
80-250
130-324
7.5
>250

>324

e) DISINTEGRATION TESTING:- For tablets the most important step toward solution is
breakdown of the tablet into smaller particles or granules is known as disintegration.
- USP device to test disintegration time uses 6 glass tubes that are 3 inches long, open at the
top & held against a 10 mesh screen at the bottom end of the basket rack assembly.
- The assembly containing tablets move up & down through a distance of 5 to 6 cm. at a
frequency of 28-32 cycles /min.
For conventional tablets and capsules
Method. Unless otherwise stated in the individual monograph, introduce one tablet or capsule into
each tube and, if directed in the appropriate general monograph, add a disc to each tube. Suspend the
assembly in the beaker containing the specified liquid and operate the apparatus for the specified
time. Remove the assembly from the liquid. The tablets or capsules pass the test if all of them have
disintegrated. If 1 or 2 tablets or capsules fail to disintegrate, repeat the test on 12 additional tablets
or capsules; not less than 16 of the total of 18 tablets or capsules tested disintegrate. If the tablets or
capsules adhere to the disc and the preparation under examination fails to comply, repeat the test
omitting the disc. The preparation complies with the test if all the tablets or capsules in the repeat test
disintegrate.

Uncoated tablet should have disintegration time not more than 30 mins.& enteric coated
tablets should show no evidence of disintegration after I hr in simulated gastric fluid.
f) DISSOLUTON TESTING:It is done to find out the drug release For dissolution testing USP apparatus 1(basket)& USP
apparatus 2 (paddle) are used.
Conventional and prolonged-release solid dosage forms
Place the stated volume of the dissolution medium, free from dissolved air, into the vessel of the
apparatus. Assemble the apparatus and warm the dissolution medium to 36.5 to 37.5. Unless
otherwise stated, place one dosage unit in the apparatus, taking care to exclude air bubbles from the
surface of the dosage unit. When Apparatus 1 is used, allow the tablet or capsule to sink to the
bottom of the vessel prior to the rotation of the paddle. A suitable device such as a wire of glass helix
may be used to keep horizontal at the bottom of the vessel tablets or capsules that would otherwise
float.
When Apparatus 2 is used, place the tablet or capsule in a dry basket at the beginning of each
test. Lower the basket into position before rotation. Operate the apparatus immediately at the speed
of rotation specified in the individual monograph. Within the time interval specified, or at each of the
times stated, withdraw a specimen from a zone midway between the surface of the dissolution
medium and the top of the rotating blade or basket, not less than 10 mm from the wall of the vessel.
Except in the case of single sampling, add a volume of dissolution medium equal to the volume of
the samples withdrawn. Perform the analysis as directed in the individual monograph. Repeat the
whole operation five times. Where two or more tablets or capsules are directed to be placed together
in the apparatus, carry out six replicate tests.
For each of the tablet or capsule tested, calculate the amount of dissolved active ingredient in
solution as a percentage of the stated amount where two or more tablets or capsules are placed
together, determine for each test the amount of active ingredient in solution per tablet or capsules and
calculate as a percentage of the stated amount.
Acceptance criteria

COATERS:OBJECTIVES OF COATING: To mask taste ,odor, colour , of the drug.

To provide physical & chemical protection to the drug.
To control release of the drug from the tablet.
To protect drug from gastric environment.
To avoid chemical incompatibilities.
To provide physical elegance.
Most coating processes use one of three general types of equipment.

(1) Standardized coating pan

Consists of a circular metal pan mounted angularly on a stand
Rotated on its horizontal axis by a motor
Heated air is directed into the pan & onto the tablet bed surface & is exhausted by means of ducts
positioned through the front of the pan.

 Coating solutions are applied to the tablets by ladling or spraying the material unto the rotating
tablet bed.
Improvements in drying efficiency of the standard coating pan can be achieved by
a) Pellegrini pan :- it has a baffled pan & a diffuser that distributes the drying air uniformly over the
tablet bed surface.
b) Immersion sword system:-In this drying air is introduced through a perforated metal sword device
that is immersed in the tablet bed.
c) Immersion tube system.:- In this a tube is immersed in the tablet bed.the tube delivers the heated
air & a spray nozzle is built in the tip of the tube.
2) Perforated coating pan :All equipments of this type consists of a perforated or partially perforated drum that is rotated on its
horizontal axis in an enclosed housing. It include following equipments
a) Accela cota & Hi coater system :-Drying air is directed into the drum ,is passed through the tablet
bed & is exhausted through perforations in the drum.
b) Driacoater :- It introduces drying air through hollow perforated ribs located on the inside
periphery of of the drum. As the coating pan rotates the ribs dip into the tablet bed & drying air passes
through & fluidizes the tablet bed.
c) Glatt coater:It is the latest one .Drying air can be directed from inside the drum through the tablet bed & out an
exhaust duct,alternatively with an optional split chambered plenum,drying air can be directed in the
reverse manner up through the drum perforation for partial fluidization of the tablet bed.
In all four types of these perforated pan systems, the coating solution is applied to the surface of the
rotating tablets through spraying nozzles that are positioned inside the drum.Perforated pan coaters
can be completely automated for sugar & film coatings.
3)Fluidized bed coater: Fluidization of the tablet mass is achieved in a columnar chamber by the upward flow of drying
air.
The air flow is controlled so that more air enters the center of the column, causing the tablets to
rise in the center.
The movement of tablets is upward in the center of the chamber & then fall toward the chamber
wall ,move downward to reenter the air stream at the bottom of the chamber.
Coating solution are continuously applied from a spray nozzle located at the bottom of the
chamber or are sprayed onto top of the cascading tablet bed by nozzles located in the upper region of
the chamber.
Examples:- Glatt FBCoater, Aeromatic FBCoater, Huttlin kugel Coater
Different approaches of FB Coater 1) Top spray
2) Bottom Spray (Wurster Process)
3) Tangential spray (Rotor process)
Spray application systems:a) High pressure, air less
b) low pressure , air atomized
Tablet coater : ( S.O.P. for Tablet coater)
1. Make sure that it is completely free from previous batch contamination.

2. Check the necessary arrangements like power supply.

3. Place a coating pan on the coating machine.
4. Put the power on.
5. Allow the pan to run for some time so that to attain suitable temperature (aqueous coating: 700C
and organic coating: 45 to 500C).
6. Load the tablet in the coating pan, till of its volume of the pan.
7. Rotate the tablet and see the cascade movement.
8. Spray the tablet with the coating solution manually.
9. Check the weight gain after some time and proper coating is taking place or not.
10. If proper weight gain achieved than stop spraying the solution.
11. Rotate coated tablet for 15 min so that it will dry.
12. Deload the pan.
13. Clean the equipment.
14. Affix the label of cleanliness.

Validation:
What is Validation?
Documentation Programme.
provides high degree of assurance.
To check correctness of method or process.
Why validation is required?

Required by law.
To avoid possibility of rejection or
recalled batches.
To ensure product uniformity, reproducibility & quality
Validation of facilities, equipment and services is called qualification
A) Installation qualification (I.Q.)
Performance of the tests in order to confirm that a piece of equipment is installed properly.
B) Performance qualification (P.Q.)
Test to demonstrate the effectiveness and reproducibility of a process.
Validation is done for:

[1]

Raw material
Process
Product
Product Validation:
Raw Material
Packaging Material
Granules
Compressed Tablets
Coated Tablets
Packed Final Product
Finished product validation:

Organolaptic property
Physical characteristic
Chemical characteristic
Biological characteristic
Microbiological characteristic
Stability testing
Storage condition
(2]Raw material validation:
Raw material is validated for particle size, surface area, particle size distribution, colour ,
Appearance, texture, density, flowability ,compressibility etc.
[3] Process validation:

Documentation .
Documentation includes
1) Raw material records. Receipt, Issue or disposal
2) Labels & Printed packaging material records.
3) Master formula records
4) Batch production records ( BMR & IP control record.)
5) Standard operating procedures. (SOP)
Batch manufacturing record:
BATCH MANUFACTURING RECORD

Product name :-_____

Generic Name :-_____
MFR Ref. No. :-______
Date of Starting:-____
Time of starting:- ______

Sr.
No.

Ingredients

Batch no.:-_____
Batch Size:-_____
Date of Completion:-___
Time of Completion:-______

Quantity Required
per tablet qty per
(mg)
batch(kg)

Analytical report
no.

Total qty.
Raw material calculation
Checked by:-

Approved by:-

SOP for weighing operation

Weighing operation

Product name :-_____

Generic Name :-_____
MFR Ref. No. :-______
Date of Starting:-____
Time of starting:- ______

Procedure:Precautions:-

Batch no.:-_____
Batch Size:-_____
Date of Completion:-___
Time of Completion:-______

The format remains same for mixing , granulation, drying, compression.

Master Formula:
MASTER FORMULA SHEET
Patent /Proprietery name __________________
Batch no._________
Generic name of product__________________
Batch size_________
Reference code___________________
Type of dosage form______________
Strength______________
Sr. no.
Ingredient
Qty. per one
Qty. per batch
Analytical report no. of ingredient
tablet(mg)
(kg)

Total

Expected final yield_________

Acceptable final yield________
Processing location

Limit
Equipment to be used

Method to be used
Processing instructions(detailed and stepwise)

Time taken for each steps

In process quality controls

Limit

Storage conditions of the products, including the container, labeling and special storage conditions where applicable
Any special precautions to be observed
Packing details and specimen labels.

Raw material requirement calculation :Actual potency of raw material may vary each time. So calculation of required quantity is done
according to raw material analytical report .
FINISHED PRODUCT TESTS
1. Dissolution test
2. Content uniformity test
3. Assay
BATCH PACKAGING RECORD
Date:______________
Product name:_______________
No: ________________
Packaging Description:__________
Quantity of packing material received( PM store) :___________________

Batch

IPQC record
IN PROCESS QUALITY CONTROL TESTS
1.Weight variation test

Weight of tablets

1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
2. Diameter
1.
2.
3.
4.
5.
Avg.

1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
4.Thickness
1.
2.
3.
4.
5.
Avg.

7.Disintegration test
1.
2.
3.
4.
5.
6.
Avg.____________
Conclusion________
_________________

11.
12.
13.
14.
15.
16.
17.
18.
19.
20
5.Hardness test
1.
2.
3.
4.
5.
Avg.
Conclusion____________

Total weight of 20. Tabs._________

Avg. weight of 20. Tabs._______
Theoretical weight of 20. Tabs.__________
%difference allowed ______________
Lower limit____________
Upper limit___________
No. tabs deviating the upper limit__________
No. of tabs. Deviating lower limit_________
Conclusion__________________________________
6.Friability test
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.

11.
12.
13.
14.
15.
16.
17.
18.
19.
20

Weight of tablets before tests

(A)___________
Weight of tablets after tests(B)____________
% Weight loss =
(A-B)/100=____________

RESULT
Parameter
1.Surface roughness
2.Cracks
3.Pinholes
4.Pinholes
5.Color
6.Polish
7.Weight variation
8.Avg hardness
9.Avg. thickness
10.Avg. diameter
11.Disintegration time
12.Friability tests

Observation
___________________________________
___________________________________
___________________________________
___________________________________
__________________________________
____________________________________
_____________________________________
_____________________________________
_____________________________________
____________________________________
_____________________________________
_______________________________________
Checked by

Format of SOP

CLEANING TICKET:

Name of the equipment_____________

last product handled _______________
Lot No_______
Cleaned & Ready for product _________
Lot No_______
Cleaned By _____________________
Date____________
Supervisors signature_______________ .

MANUFACTURING REQUIREMENTS & PRECAUTION TAKEN FOR THE

MANUFACTURING OF HORMONAL TABLETS:We require special requirements & precautions for the manufacturing of hormonal drugs as
these drugs are very sensitive & are harmful when inhaled

These products may produce harmful effects like cancer & generally male workers are
involved in manufacturig areas so while handling tablets containing female hormones if they
come in contact with these products they may develop female charateristics..
Separate premises is reqd for their manufacturing
Separate laundry is reqd
Persons involved in manufacturing should cover themselves completely.
Respirator mask should be worn to prevent inhalation.
Ahu,hepa,hvac etc used in conventional tablets manufacturing supply recirculated air but in
case of hormonal tablets it is not tolerated no air is circulated but rather air after entering the
area has to go out. & 100% exhaust system is necessary
Air that goes out should be filtered otherwise it may pollute the environment & may affect
other people..
Separate documents are to be prepared exclusively for hormonal tablets.
Disposal of rejected hormonal tablets:Failed tablets are dissolved in 4% naoh solution instead of pure water and drained in
sewage
Counterfeiting of tablets: Tablets are packed only after ipqc testing but there are chances that before packaging & after
ipqc tablets are peplaced with fake ones..
This is a major point of concern and so to detect & prevent this no. Of techniques are coming
up.
Techniques used are:1. Raman spectroscopy
2. Near ir spectroscopy
CURRENT RESEARCHES:
2.2. Solventless coating:
2.2.1. Introduction:
The liquid coating process and equipment have been well established and widely adopted by the
pharmaceutical industry.
The liquid coating technology can obtain exceptionally uniform smooth lustrous coating surface.
However, the inherent disadvantages caused by using organic solvents or water have become
increasingly obvious7, 8, 9.
Firstly, vaporizing organic solvents or water is energy consumptive, which adds a large bill to the
coating cost; secondly, long processing time up to hours and even days is essential for liquid
coating to get a dry, uniform, and smooth coating surface; in addition, using organic solvents
results in environmental pollution, solvent recycling cost and operation dangers of explosion;
finally, organic solvent itself imposes another cost to the coating process in addition to the
energy-consumption and long processing time.
In order to overcome these limitations of the liquid coating technology, new efforts have been
made in recent years to develop solventless coating technologies.
2.2.2. Techniques of solventless coating:
1. Hot-melt coating

2. Supercritical fluid spray coating

3. Photocuring coating
4. Powder coating10

2.2.3.

Methods which completely avoid the use of solvents:

1. In one such method, a thermoplastic or thermo-melting material, such as wax, is applied by

spraying or by melting and causing it to adhere to a previously heated material which it is
desired to coat.
Disadvantage: That the coating material is limited to materials which can melt or are thermoplastic, such
as wax, and there are few materials which can be used within the temperature range of
from 20 C. to 70 C., which is commonly employed in the coating of pharmaceuticals.
2. Another solventless coating method comprises charging a powdered coating material and the
material to be coated with static electricity, to cause the coating material to adhere. This has
the disadvantage that charging these materials with static electricity requires the use of very
expensive equipment.
In summary, of the two types of technique which have been proposed, the old-established
technique of using organic solvents is inherently undesirable and can be expensive, the
technique using water is difficult to operate and can give rise to stability problems
(especially when used with pharmaceuticals).
There is, therefore, a need to provide a relatively inexpensive coating technique which
avoids the safety problems of the technique using organic solvents avoids the various
stability problems of the technique using water and avoids the problems associated with
the known solventless techniques3.
Among these solventless coating techniques, powder coating technique, which is often
termed as dry coating in the pharmaceutical coating fields, is the most widely studied
one and has not been elaborated4.
2.2.4.

Types of solventless coating:

1. Dry coating
2. Compressed coating
3. Other coating techniques includes;
a. Hot-melt coating
b. Supercritical fluid spray coating
c. Photocuring coating

2.2.4.1.

Dry coating:-

Dry coating is a coating technology for solid pharmaceutical dosage forms derived from
powder coating of metals. In this technology, powdered coating materials are directly
coated onto solid dosage forms without using any solvent and then heated and cured to
form a coat.
The concept of powder coating originated in the USA in 1950s

11

and significant growth

has been achieved in the metal and wood finishing industries over the last two decades.
More and more liquid coatings are being replaced by powder coatings due to the
drawbacks of liquid coatings similar to those described above.

Importance of Dry coating:

This technology can overcome such disadvantages caused by solvents in conventional
liquid coating.

Such as, air pollution, high time- and energy-consumption and expensive operation cost
encountered by liquid coating.

Liquid coating vs. powder coating:

Figure 15: Difference between Liquid coating and Dry coating.

Fig 15 describes some basic step of liquid coating and powder coating. In liquid coating huge
energy is use for evaporating solvent, while in case of powder coating; energy savings can be
achieved due to absence of liquid evaporation step. 14, 15.

Dry coating technologies

1. Plasticizer-dry-coating
2. Electrostatic-dry-coating
3. Heat-dry-coating

4. Plasticizer-electrostatic-heat-dry-coating

Principles of powder coating technologies:

The principle of the powder coating technology involves spraying of a mixture of finely
ground particles and polymer onto a substrate surface without using any solvent, and then
heating the substrate in a curing oven until the powder mixture is fused into a coating film.
Four different powder coating processes have been developed. They are: electrostatic
spraying, fluidized bed coating, electrostatic fluidized bed coating and flame spray, among
which electrostatic spraying is the most common process used for application of powder
coating.
The basic principle of electrostatic spraying concerns propulsion of the dry powder by
compressed air through a spray gun, by which it becomes electrically charged and then moves
and adheres to the earthed substrate surface. A successful electrostatic spraying should satisfy
several requirements: a powder charging/dispensing unit, an earthed conductive substrate and
powder particles able to be charged.
There are two types of spraying units, generally in the form of powder charging guns,
according to the charging mechanisms:
1. Corona charging
2. Tribo charging
Corona charging guns are characterized by electrical breakdown and thereafter ionization of
air by imposing a high voltage on a sharp pointed needle-like electrode (i.e., charging pin) at
the outlet of the gun, and the powder particles picking up the negative ions on their way from
the gun to the substrate, while tribo charging guns make use of the principle of frictional
charging associated with the dielectric properties of solid materials and therefore no free ions
and electrical field will be present between the spray gun and the grounded substrate.
The movement of the particles between the charging gun and the substrate is mainly governed
by a combination of electrical and mechanical forces. The mechanical forces are produced by
the air that blows the powder towards the substrate from the spray gun. For corona charging
guns, the electrical forces are derived from the electrical field between the charging pin of the
spray gun and the earthed substrate, which push the charged particles towards the grounded
substrate and from the repulsive forces between the charged particles. For tribo charging
guns, the electrical forces are only regarded to the repulsive forces between the charged
particles.
For both corona and tribo spraying processes, when the charged particles move into the space
adjacent to the substrate, the attraction forces between the charged particles and the grounded
substrate will make the particles to deposit on the substrate.
Three steps for the charged powder particles to absorb onto the substrate surface are involved
12

1. Firstly, charged particles are uniformly sprayed onto the earthed substrate in virtue of
mechanical forces and electrostatic attractions;
2. Thereafter, particles accumulate on the substrate before the repulsion force of the deposited
particles against the coming particles increases and exceed the electrostatic attraction of the
earthed substrate to the coming particles.
3. Finally, once the said repulsion becomes equivalent to the said attraction, particles cannot
adhere onto the substrate any more, and the coating thickness does not increase any more.
Compared with the traditional liquid coating technology, the powder coating technology is
highly valued for energy and time savings, nearly 100 % utilization of the coating materials,
long shelf life, environmental friendliness, safety and therefore low overall operation costs 7-9,
13

. Furthermore, the coating process is simplified because important parameters of liquid

coating processes have not to be considered, e.g., evaporation parameters.

Applications of the powder coating technology have been successful in metal and wood
finishing, which has enlightened new application in the pharmaceutical industry to coat solid
dosage forms.

Procedure for dry powder coating:

Fig. 16: Flow chart for dry powder coating

Fig 16 describe how powder coating take place .it include different steps like heating source
for preheat solid dosage form, then liquid atomizer to spray plasticizer. If there is no need of

Plasticizer then spraying charged powder material on the earthed dosage form by electro static
spray gun and finally curing the product16.
Recent addition in tablet press system:
FETTE PREFECTA 2000 COOLTEX
Enables the compression of the substance at low temp
This cooling unit allows for the preparation by compression of suppositories, enzyme
preparations or thermo sensitive active ingredients.
-60C temp is attainable by the press.
Multi layer tablet press
Ability to produce Three layer, Two layer and ordinary tablets.
Sampling facility for checking the weight of individual layer.
Totally enclosed centre drive system for turret. Pre-compression to improve compressibility and
quality of tablet.
Adjustable upper punch penetration.
Facility for easy and faster change over of lower punches and dies.
Force feeding systems to maintain the uniform filling and precise weight.
Common drive for three force feeders.

(Multi layer tablet press)

Zero clearance force feeder, Efficient dust extraction system to avoid layer mixing.
Overload pressure release and sampling mechanism through hydraulics.
Spray lubrication
Lubricant in the tablet is problematic when less disintegration time is required.
This can be overcome by Gentle blending of tooling with lubricant
Swabbing of the machinery with lubricant
This also can be done by spraying lubricant solution on the tools
This can also reduce tooling wear

Excipients with trade name

Directly compressible diluents

QUESTIONS
1) What is granulation? Describe wet granulation with equipments?
2) Define, classify give Manufacturing equipment, plant layout and validation of tablet ?
3) Develop a different plant layout for tablets & gives a best layout for manufacturing of tablets
with appropriate reasons.
4) What are objective of coating? Explain different coater?
5) What is validation? Describe different types of validation with reference to tablet production?
6) A hormonal tablet is to be developed with a label claim For oral/ vaginal use, suggest possible
API contained into the dosage form. Developed a manufacturing protocol for it & discuss in detail.[
Guj uni-2007]
7) An Enterprenes wants to market his product as effervescent granular powder containing
lactobacillus spores in sachet packing, suggest manufacturing facilities with layout , equipment ,
packaging & SOP for various stages.[ Guj uni-2007]
8) What is coating? Describe different method of coating with equipments?
9) Classify dryers? Describe in detail about FBD?
10) Write a note on documentation needed in tablet manufacturing technique.
11) Write short note on
A) BMR
B) BPR
C) SOP

VI. REFRENCES:1.
2.
3.
4.
5.
6.

The theory and practice of industrial pharmacy by Lieberman ,lachman, Kanig

TABLETS volume 3
Encyclopedia of pharmaceutical technology Marcel Dekker ,vol-6
Pharmaceutical process validation by Loftus and.Nash
Pharmaceutical Sciences by Remington
Drugs and Cosmetics Act by Vijay Malik , pg no 410
Quality assurance manualwww.pharmatech.com
www.bioprocess.com
www.sotex.com
www.pharmamachine.com
www.stablemicrosystem.com
www.celisinstrument.com
www.tablettesting.com
www.mocoa.com
www.pubmed.gov
www.equinet.in