SOLID DEPARTMENT

5
Tablet Section

DEFINITION OF TABLET
Tablets are solid dosage forms containing a single dose of one or more active
ingredients & obtained by compressing uniform volumes of particles. They are intended
for oral administration.

Tablets are usually rigid, circular solid cylinders, the end surfaces of which are flat or
convex and the edges of which may be rounded. They may have break-marks and may
bear a symbol or other markings. Tablets are also coated in cases of special demands on
release patterns and also to enhance stability and to protect them from environmental
and microbial damage.

6
Different types of tablets:

• Immediate release tablets, designed to release the drug immediately

Immediate after ingestion.
release tablets

• Delayed or modified release tablets, where the drug is not released until
Delayed or a physical event has occurred, e.g. time elapsed release or releasing in
modified the intestine to avoid gastric pH.
release tablets

• Chewable tablets and lozenges, to provide great feeling in the mouth

Chewable and for local delivery in the mouth or throat.
tablets and
lozenges

• Sublingual tablets, designed to be placed under the tongue for rapid

dissolution.
Sublingual
tablets

• Effervescent tablets, that forms an effervescent, leaving a pleasant taste

Effervescent in the mouth.
tablets

• Dispersible or soluble tablets, which when taken in water, form a

Dispersible or suspension or solution for ease of swallowing.
soluble tablets

Excipients of Tablets:
a) Diluent or Filler: Filler, such as sucrose or lactose, avicel, maize starch is
included to increase the size of the tablet. Maize starch is used most often as it
is cheap and easily available. This is necessary as often the amount of 'active' is
so tiny that the tablet would be too small to handle without it.

b) Binder: A binder, such as glucose or sucrose , avicel , povidone K30,maize

starch, is added to hold the tablet together after it has been compressed,
stopping it from breaking down into its separate ingredients.

7
c) Disintegrant: Disintegrants help the tablet to break down into small fragments,
when it is ingested. This helps the medicine to dissolve and be taken up by the
body so that it can act more quickly. Disintegrants may include potato or cocoa
butter, Na-starch glycolate, cross povidone.

d) Lubricant: Lubricants are the agents which are used to reduce friction among
the lower and upper punch of the machine during compression. It ensures that
the tablet has a smooth surface and the powder does not stick to the
equipment used to make the tablet. For example Mg stearate, purified talc,
aerosol 200.

e) Glidant: Glidants are the agents which are used to improve flow properties of
the powder mixture. It helps to keep the powder for the tablet flowing
continuously from the hopperas the tablet is being made, stopping it from
forming lumps. For example talc, colloidal silica etc.

f) Coloring agent: Colors are added to help you to recognize your tablet and to
make it easier to take your medicine correctly

g) Flavoring agent: Flavoring agents help to make the tablet taste better.

h) Anti-adherent: The anti-adherent also stops the powder from sticking to the
die holes and die punches as the tablet is compressed.

FIGURE: COMPOSITION OF TABLET

8
PRODUCTION OF TABLET
In tablet production there are several steps involved which are following:

Dispensing

Granulation

Powder compression
For
Coating Uncoated
Tablets

Blistering

Secondary packaging

Granulation Unit
Granulation is the process in which the powder particles of raw materials are
made to form larger particles in order to facilitate compression for the production of
tablet. All the materials are received from the dispensing unit and granulation is
performed. For suitable granulation, it is required to have 30-40% powder and 60-70%
granules and also 1-5% moisture in compressing particles. In granulation process, these
are maintained accurately according to the QC provided specifications.

1. To improve flow properties of

the mixture
Reasons for 2. To prevent segregation of the
constituents in the powdered
granulation mixture
3. To improve compression
characteristics of the mixture

9
Granulation Process

• Wet granulation.
There are three • Dry granulation.
process of • Direct compression or dry
granulation mixing.

Wet Granulation
This is the most widely used and most general method of tablet preparation. The wet
granulation of tablet production is essentially a process of size enlargement, sticking
particles of drug and excipients together using an adhesive to produce a granular
product with improved flow properties and increased ability to cohere under pressure.

10
Flow diagram of wet granulation:

Weighing of active ingredient as well as excipients

Dry mixing

Addition of Binder in solution form

Preparation of wet mass

Initial Drying

Milling in multimill

Partial Drying

Milling in Multimill Again

Terminal Draying

Final size reduction

Measurement of LOD

Granules ready for Compression

11
Dry granulation

This process is applied for those drugs which are sensitive to moisture. This process is
also used for water sensitive or hygroscopic powder that needs granule formation
before compression.

Flow Diagram of Dry granulation:

Weighing of drugs and excipients

Dry mixing of drugs and diluents

Slugging or pre-compression

Milling and sieving

Lubrication

Discharge for compression

Direct compression
Tablets are produced directly from the powder by compression without modifying the
physical nature. It is done for only few selective drugs, which has crystalline nature.
Flow Diagram of Direct Compression

Weighing of active and exicipients

Mixing of all ingredients

Milling or Sieving

Discharge for compression

12
Condition for manufacturing of Granules:
 Relative Humidity: Not more than 55% (depends on the nature of the product).
 Temperature: Below 250C.

Machineries used in Granulation Unit:

Name of the machines Purpose
Planetary mixer To mix the active ingredient and
Origin: India, Gansons Company binder to form granules.
Capacity: 60 kg
Fluid bed dryer To Dry granules.
Origin: Bangladesh
Capacity: 60 kg
Multi mill To reduce the size of granules.
Origin: India and Bangladesh
Capacity: RPM 1400-2700
Rapid Mixture and Wet Granulator To mix the active ingredient and
Origin: India binder to form granules.
Capacity: 160 Kg To Dry granules.
Double cone blender To mix uniformly all the excipients.
Origin: Bangladesh
Capacity: 250 kg ,rpm 18-20
IBC blender (intermediatory bulk) To mix all of the ingredients uniformly
Origin: Bangladesh and to form granules
Capacity: 140kg to 350kg or 400L to 800L
Drum blender To mix ingredients

Shifter Machine To shift mixtures from one equipment

to another.

13
 Fluid bed dryer

Rapid mixing granulator(RMG)

Fluid Bed Processor To complete all of the process of wet

Origin: India granulation and make granules
Capacity: 500 litre

Mini stirrer machine To milling excipient and API

Steam vessel Generate steam to vaporize water

14
Multi miller Double cone blender

Figure: Machine of Tablet Section

15
Compression Unit

After proper blending, granules are stored in a container and then it is delivered to the
compression unit fornoisseppmoc . Then the granules are compressed to form tablets of
specified weight, hardness, and thickness.

Flow chart of compression process:

Upper punch is raised and lower punch has dropped

Granules fall into die cavity

Upper punch comes down and compresses granules into tablet

Upper punch has moved back ward

Lower punch has moved upward

Tablet is ejected

16
Before compression following parameters are checked:

1. Proper cleaning of machine.

2. Proper arrangement of die and punch.
3. Removal of all the material relevant to previous product
4. HVAC system.
5. Dust collecting system
6. Humidity
7. Temperature
8. Pressure differential
9. Granules are poured into hopper

Major parts of Compression Machine:

17
 Compression Problems:
Weight
Picking and variation,
sticking Hardness
problem

Capping and
Mottling
lamination
Compression
Problems

Common Tablet Problems:

Problem Cause Remedy Figure
Chipping  Too dry granules  Moisten the
 Concavity too deep granules for
for effective plasticizing
compression.  Use of flat punches,
along with reduced
concavity

Mottling  Improper dying  Use suitable

colorant
solution
 Use of dye during
 Migration of dye to blending stage
the surface

Laminaton  Improper lubricant  Use of adsorbent or

 Rapid absorbent
decompression  Use of pre
compression step

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Capping  Low moisture  Compression at
content room temperature.
 Improper binders  Use of flat punches

Sticking  Oily or hygroscopic  Change or decrease

material the binder
 Improper concentration
lubrication  Compression under
controlled humidity

Classification of Tablet Compression Machine:

Tablet compression machines
can mainly be of 3 types:

B tooling (for compressing

small size tablets with a
barrel diameter of 19mm)

D tooling (for compressing

large size tablets with a
barrel diameter of 26mm)

DB tooling ( this makes the

smallest sized tablets)

There are total 10 tablet compression machines in ARISTOPHARMA plant:

Machineries used in Compression area:

Sl. No. Name of Model No. Origin Capacity Type

Machine
1 Cadmach CPDII-37 India TBCM-16 D

19
 compression
machine
2 Sejong MRC-30N South Korea TBCM-43 D
compression
machine
3 Sejong MRC-45D South Korea TBCM-45 B
compression
machine
4 Cadmach CMB4-35 India TBCM-44 B
compression
machine
5 Cadmach CMB4-35 India TBCM-15 B
compression
machine
6 Cadmach CMB4D-27 India TBCM-33 D
compression
machine
7 Cadmach CMD3B-23 India TBCM-13 DB
compression
machine
8 Pharmatek PTK PR3500 South Korea TBCM-16 D
compression
machine
9 Jaguar JS-16 India TBCM-12 B
Compression
machine
(Cephalosporin)
10 Tablet Station-10 India DB
Compression
machine(PD)

In Process Quality Control:

In process quality control is a system which ensures the quality of the product while it is
being manufactured. Every step of the processing of a dosage form is checked to

20
maintain a high quality end product. The whole system works on one motto, “Quality is
to be built in the product.”

During tablet IPQC, following machines are used

Machine Brand and Origin Purpose

Weight Balance(uniformity Sartorius, Switzerland To determine the RSD

Test) (relative standard
deviation) of weight of the
tablet.
Moisture Analyzer MA-35, Sartorius, To measure the moisture
Switzerland content of a tablet
Hardness tester India, Capacity-10 tab/min To measure hardness and
thickness of tablet (Interval-
2 hr.).
Friabililty tester Electrolab, India To measure friability
(100rpm/4min.) or ability to
withstand stress.
USP Apparatus II Electrolab, India To determine whether the
dissolution tester dissolution of the tablet
meets the requirement or
not

21
 Weight Balance Friability Tester

Hardness Tester Dissolution Tester

Figure: Equipments used by IPQC

22
Coating Unit

TABLET COATING:
Coated tablets are tablets covered with one or more layers of mixtures of various
substances such as natural or synthetic resins, gums, gelatine, inactive and insoluble
fillers, sugars, plasticizers, polyols, waxes, colouring matter authorized by the competent
authority and sometimes flavouring substances and active substances. The substances
used as coatings are usually applied as a solution or suspension in conditions in which
evaporation of the vehicle occurs. When the coating is a very thin polymeric coating, the
tablets are known as film-coated tablets.

Coated tablets have a smooth surface which is often coloured and may be polished; a
broken section, when examined under a lens, shows a core surrounded by one or more
continuous layers with a different textures.

Objectives of tablet coating:

1. To mask the bad taste, odor or colour of the drug.
2. To protect moisture sensitive drugs from moisture.
3. To provide physical and chemical protection of the drug.
4. To control the release of the drug from the tablet.

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 5. To protect the drug from the gastric environment of the stomach with an acid
resistant enteric coating.
6. To incorporate another drug or adjuvant in the coating to avoid chemical
incompatibilities or to provide sequential drug release.
7. To improve the pharmaceutical elegance by use of special color or contrasting
printing

Conditions for Tablet Coating

Distance
between
spray gun
and tablet
bed

For aqueous
coating 3-4
Air
Conditions for inch & for
pressure
Tablet Coating organic
1.5-4 kg
coating 8
inch

Rotating pan
rpm within 3-
15/hr.

Steam temperature:

Type Inlet Exhaust

Aqueous (45-75)˚ C (35-55)˚ C
Organic (35-65)˚ C (30-50)˚ C

Classification of Coating:
Mainly three types of coating are performed in the solid section. They are as
follows:

24
 Aqueous coating

Film coating

Organic coating

Coating Sugar coating

Enteric coating

Sugar Coating:
It is one of the oldest and most commonly used methods of coating the tablet on
a commercial scale. It is used to mask the unpleasant taste and odor, to improve the
appearance and to protect the ingredients from decomposition on exposure to air and
moisture. In suitable sugar coating equipment , the tablet cores are successively treated
with aqueous sucrose solutions which depending on the stage of the coating reached ,
may contain other functional ingredients e.g fillers ,colors etc.

Stages of Sugar Coating:

The various stages involved in sugar coating are:
1. Sealing or water proofing ( this provides a protection layer and is done using Opa
dry and purified talc )
2. Sub-coating (this is the main sugar coat and is done using sucrose, emulsifying
agent, gelatine as surfactant, purified talc, titanium dioxide, glycerine as
plasticizer and water as solvent )
3. Smoothing
4. Colouring and finishing ( this is done using OPA Lux and purified talc )
5. Polishing (this is done using carnauba wax)

25
Sugar coating machine:

There is one sugar coating machine in this coating unit. Two pans are involved in this
machine which are called pan1 and pan2.

Sl.No Name of machine Orgin Capacity

1 Sugar coating pan Bangladesh 100 kg
machine

Film coating:
In film coating two polymers are highly used. One is HPMC and another is Eudragit-L100
and L-50 (liquid). In aqueous solution water is used as solvent but in organic solution –
methanol, methylene chloride and PEG 6000 are used. Povidone K30 is used a binder so
that the coat sticks to the tablet surface. An opacity enhancer and light protector is also
used. The distance between spray gun and tablet bed, in case of organic solvent is 3-4
inch and in case of aqueous solvents is 8 inch. Air pressure is maintained to 1.5-4 kg.

Steam temperature:

Inlet temperature: 50-65˚ C

Outlet temperature: 35-50˚ C

Process of Film Coating:

Step 1: Preparation of Coating Solution

Preparation of polymer dispersion

Mixing until complete dispersion Filtration
Preparation of pigment suspension

26
Step 2: Coating process

Tablet to be coated
place in the coating
pan.

Inlet, outlat, bed temperature

& pan RPM are adjusted.

Coating solution is
spryed on the tablet bed
by a spry guns.
Coating

Drying

27
Enteric coating

It is a special type of film coating used for specific purpose. The coating materials used in
this case is all the same as normal film coating except that, an additional layer of an
enteric coating material is used with the coating material. The mostly used enteric
coating materials are Cellulose Acetate Phthalate (CAP) and Shellac.

There are two steps for enteric coating:

1. Sub-coating: Sub coating is performed by using HPMC as polymer with either

organic or aqueous solution. Isopropyl alcohol and methylene chloride is used
as solvent and Povidone K30 is used as a binder. This process performs for 5
hours.

2. Enteric coating: Organic enteric coating is performed by using opar dye enteric
(white), cellulose acetate phthalate or metha crylate 10 as polymer. Aqueous
enteric coating is perfoemed using kollicoat MAE 30 DP as polymer, an
opacifying agent, talc, propylene glycol as plasticizer and water over the sub
coating. This is done for 15 hours.

Parts of Coating Machine:

1. Switch
2. Inlet (lets in hot air )
3. Perforation (allows hot air to pass out of the pan across the tablets )
4. Baffle ( allows proper mixing of tablets with solution )
5. Exhaust
6. Spray Gun ( sprays coating solution in the form of drops with the help od
compressed air )
7. Peristaltic pump ( pulls suspension up into spray gun )

28
Machineries used in Coating unit:
Machine Name & Origin Capacity and Purpose

NR-Cota-I Capacity: 100 kg (60-110)

Code no: TC-TC-9 Film coating
Origin: Thailand Spray Gun: 2
NR-Cota-II Capacity: 100-130 kg
Code no: TC-TC-11 Film and enteric coating
Origin: Thailand Spray Gun: 3 7hrs. To complete 1 Batch.
ECO-Cota Capacity: 60kg
Code no: TC-TC-2 Film and enteric coating
Origin: Pakistan Spray Gun: 2
RAMA-Cota Capacity: 5-20 kg
Code no: TC-TC-1 Film coating
Origin: Thailand Spray Gun: 1
TCM (PAM-GLATT) Capacity: 400 kg
Code no: GCS 500 Autocoater Film coating
Origin: India (German Technology) Spray Gun: 5

Condition required during Coating:

Relative Humidity
• Not more than 50%.

Temperature
• Below 250C.

C ONDITIONS OF TABLET COATING

Distance between spray gun and tablet bed: 15-22 cm

For aqueous coating:

 3-4 inch For organic coating

29
 2-10 inch Rotating pan rpm
 Within 3-10/hr.
Air pressure 3-5 Bar

Steam pressure:
Inlet outlet
Aqueous 450 – 750 c 350- 550 c
Organic 35o - 65o c 30o- 500 c

Sugar Coating Machine Dria Coater Machine

Enteric Coating Machine (PLC)

30
 COMMON PROBLEMS ASSOCIATED WITH TABLET COATING:

1. Logo Bridging

Cause:
a. Surface characteristics of the product being coated
b. Inadequate adhesion of film coating
c. Inadequate design of logo (e.g. too detail/fine logo)

Remedy:
a. Modify core formulation to include more hydrophilic ingredients
b. Increase core porosity
c. Using formulation with increased adhesion property.
d. Increase area within the debussing and modified angles.

2. Core Erosion

Cause:
a. Inherent softness or high friability of core.
b. Excessive pan speed in coating process.
c. Spray rate too low.

Remedy:
a. Increase mechanical strength of core.
b. Decrease pan speed.
c. Increase spray rate.

3. Edge Chipping/Erosion

Cause:
a. Low mechanical strength of coating
b. Excessive pan speed
c. Low solid content in coating liquid
d. Low spray rate
e. Sharp edges on tablets
f. Worn tablet punches

31
Remedy:
a. Using formulation with increased mechanical strength
b. Decreased pan speed
c. Increase solid content in coating liquid
d. Decrease spray rate
e. Use modified punch design

4. Picking/sticking:

Cause:
a. Spray rate too high
b. Inadequate drying condition
c. Pan speed too low
d. Inadequate atomization of coating liquid
e. Poor distribution of coating liquid

Remedy:
a. Decrease spray rate
b. Increase drying condition
c. Increase pan speed
d. Increase atomizing air pressure/volume
e. Increase number of spray gun

5. Cracking

Cause:
a. Low mechanical strength of coating, exacerbated by inadequate
plasticization, excessive pigmentation.
b. Core has significantly different thermal expansion characteristics than
coating.
c. Extended strain relaxation of core after compaction.

Remedy:
a. Selecting formulation with increased mechanical strength and elasticity
properties.
b. Avoid use of mineral type fillers (e.g. CaCO3, CaSO4, MgCO3 etc.)

32
 c. Extend holding period of tablets prior to submitting them to coating
process.

6. Peeling

Cause:
a. Low mechanical strength of coating
b. Poor adhesion of coating to tablet surface

Remedy:
a. Using ingredients of improved mechanical strength.
b. Using ingredients with improved adhesion properties.

7. Orange peel/roughness

Cause:
a. Viscosity of coating liquid is too high
b. Poor atomization of coating liquid
c. Excessive drying condition
d. Over wetting (causing coating too rub)

Remedy:
a. Decrease solid content of coating liquid
b. Increase atomizing air pressure/volume
c. Decrease inlet air temperature/flow rate
d. Decrease spray rate

8. Twinning

Cause:
a. Spray rate too high
b. Pan speed too low
c. Inappropriate tablet shape

33
Remedy:
a. Decrease spray rate
b. Increase atomizing efficiency
c. Increase pan speed
d. Select new tablet shape that decrease chances of flat surfaces coming
into contact during application of coating liquid. (e.g. avoid capsule shape
tablet with thick side wall)

9. Tablet-to-tablet color variation

Cause:
a. Too little coating applied
b. Inadequate mixing of tablet during coating
c. Poor opacity (or hiding power)
d. Solid content of coating liquid too high
e. Insufficient number of spray gun

Remedy:
a. Increase quantity of coating applied
b. Increase pan speed/increase improve baffle system
c. Reformulate coating with respect to colored ingredients or use an
opacified white pre-coat.
d. Decrease solid contents of coating liquid.
e. Increase number of spray gun.

Tablet coating can also be classified in following 2 types in general:

Tablet Coating

1. Aqueous coating (where the 2. Organic coating (where the solvent

Solvent used is purified water) is an organic solution like methanol,
Methylene, chlorine, PEG 6000 etc.

34
Capsule Section

35
 Capsules may be defined as solid dosage forms with hard or soft shells of gelatin
or any other suitable material of various shapes and capacities, containing a single dose
of active ingredient. They are intended for oral administration. For oral administration
the capsules is placed on the tongue and swallowed with a drink of water.

The capsule shells are made of gelatin or other substances, the consistency of which
may be adjusted by the addition of substances such as glycerol or sorbitol. Excipients
such as surface-active agents, opaque fillers, antimicrobial preservatives, sweeteners,
coloring matter authorized by the competent authority and flavoring substances may be
added. The capsules may bear surface markings.

The contents of capsules may be solid, liquid or of a paste-like consistency. They consist
of one or more active substances with or without excipients such as solvents, diluents,
lubricants and disintegrating agents. The contents do not cause deterioration of the
shell. The shell, however, is attacked by the digestive fluids and the contents are
released.

Classification of Capsule:
Capsule

Hard gelatin capsules Soft gelatin capsules

Capsule sizes:
Empty gelatin capsules are manufactured in various sizes, varying in length, in
diameter and in capacity. The size selected for use in determined by the amount and
density of material to be encapsulated. The available capsule sizes in ARISTOPHARMA
are 0 (Extracet-500mg), 1 (Taxitil-100mg), 2 (Omep-20mg), 4 (Diflu-50mg) and 5 (Emep-
20mg).

36
Encapsulation Process by Automatic Capsule Filling Machine:

Encapsulation Process by Manual Capsule Filling Machine by Hand:

For encapsulation of powder the following procedure is done with the help of Manual
Capsule Filling Machine by hand in the capsule filling units of the industry:

Loading of capsule in the loading plate


Removal of caps of the shells

Filling of powder

Rejoining of caps of the shells

Encapsulation

Sorting of Capsules

Polishing of Capsule

37
 Encapsulation by automatic capsule filling machine:

Capsule shells are placed in the hopper

Capsules shells come in a secondary station

Shells are automatically fitted in the capsule

dies

caps and bodies seperated by vacumn

pressure

pellets are filled automatically

displaced shells are automatically sealed

Filled capsules are automatically ejected

Common problems occurred during encapsulation:

Blank shell
Shell lock in channel
Shell breaking
Improper filling of shell
Improper fitting of shell in dies if compressed air pressure is not adjusted properly

Machineries used in Capsule area:

Machine name Machine specification Manufacturer Origin
Semi auto capsule filling Capacity: 15000-16000/hr. PAM (SA-9) India
machine Capsule fill pharmaceuticals
Automatic Capsule filling Capacity: 30,000/hr. (100 Hanli Korea
machine (45) rpm) Capsule fill

38
Automatic Capsule filling Capacity: 30,000/hr. Sejong Korea
machine (SF-40) Capsule fill
S.S. Double cone Blender Capacity: 200 kg Gansons India.
Drum Blender Capacity: 90 kg Myth Bangladesh
Capsule polishing machine Capacity: 15,000- PAM (DP100) India
16,000/hr. pharmaceuticals
Shell Inserter Machine ACG-PAM (AL-90) India

In Process Quality control (Capsule):

Test Name of the Origin Purpose

machine

Leak Test Leak testing India To determine whether

Machine there is a leak in the
capsule shell or not

Dissolution Dissolution tester Electrolab, India To determine the

time dissolution time of the
capsule

Content Weight Balance Sartorius, To test content uniformity

Uniformity Germany

Locking Checked manually Checked To check the lock and key

manually mechanism of the capsule
shell

Brittleness Checked manually Checked To determine the hardess

manually of the capsule

39
Drum Blender Semi Auto Capsule Fill Machine

Double cone blender Automatic Capsule Fill Machine

40
DRY SYRUP

This is a powder dosage form of oral drug used when the drug is unstable in solution. It
must be reconstituted before use. It is mainly sugar based preparation. Certain amount
of water should be used to reconstitute it. The active is either prepared inside or
imported directly from outside that only require filling.

Flow Diagram for Dry syrup manufacturing

41
Machines used in the Dry Syrup Manufacturing unit:

Name of the Machine Function

Double cone Blender Blending/Mixing

Dust Collector Removal of dust
Powder Filling Machine Filling of Dry Syrup
Origin: USA. Capacity: 40 bottle/min
Ropp cap Sealing Machine Sealing of Dry Syrup Bottle
Model: DSC521

42
Condition for manufacturing Dry Syrup:

Relative Humidity: Not more than 50%.

Temperature: Below 270c

43