M.Sc. Industrial Chemistry III Sem.

Project Report

On

Production of DRUGS (Syrups, Tablet)

At

Biosynth Pharmaceuticals Pvt. Ltd.

Submitted a project report to S.M.S. Govt. Science College, Gwalior

For the fulfillment of M.Sc. Industrial Chemistry

Session

2007-2009

Under Supervision of Submitted to

Mr. S.C. Gupta Dr. Shadhna Shrivastava
Production Manager H.O.D. Industrial Chemistry

Submitted by
Raushan Kumar
Department of Industrial Chemistry
SMS Govt. Model Science College
Gwalior
 DECLARATION

I do thereby state that the project report entitled 'Production of drug'

submitted for fulfillment of SMS Govt. Model Science College, Gwalior not

substantially the same as the one which is already been submitted for a

degree of my other Academic Qualification of any university, to the best of

my knowledge.

Place : Gwalior Raushan Kumar

Date : 9th July 2008

 ACKNOWLEDGEMENT

The management of 'Biosynth Pharmaceutical Pvt. Ltd.' Banmore has

kindly provided me an opportunity of doing Industrial training in their

concern. I feel its my moral responsibility to express my heartiest thank to

the management of Biosynth Pharmaceutical Pvt. Ltd.

I am very much indebted to the dedicated and experienced staff

without whose guidance the completion of the report would not have been

possible. Here I am also thankful to Mr. Rajeev Kumar (Chemist) and Mr.

S.C. Gupta production manager, Mr. Maneesh Banjaree (M. Pharma) they

have properly guided me thorugh my training programme. My special thanks

to Dr. Sadhana Shrivastava (H.O.D.) of Industrial Chemistry Science

College Gwalior who is mainly responsible for my training programme at

Biosynth pharmaceutical Pvt. Ltd. Banmore.

Raushan Kumar
 INDEX

1. Introduction

⇒ Company Profile

⇒ Licenses

2. Syrup production

3. Tablet production

⇒ Manufacturing process

4. Packaging

5. Quality Assurance

6. Conclusion

7. References
 COMPANY PROFILE

Name : Biosynth Pharmaceutical Pvt. Ltd.

Address : Plot No. 81, Bammore, Industrial Area,

Banmore, Disst. Morena

M.P. India

History

The company was setup in 1981 under the guidance of Mr. R.K.

Gupta. The company started its unit with Antibiotics products like

Amoxicillin, Cloxacillin, etc. Initial Tablet and Syrup production started

with products like Amoxin 500. Syp. Bioce Syrup PCM this product they

were syp bioces, PCM, sulfamethacozol which are used for Antitussive,

Antipyratic, antibacterial.

These both Depts. Produces Antibiotics products as a job work for big

giants in Medicine.
 BRIEF WRITEUP OF COMPANY

Biosynth Pharmaceuticals is a small scales industry and is engaged in

the manufacturing of anti- products tablet, syrup and powder on loan license

basis. For this purpose it holds necessary drug manufacturing licenses

granted by the Licensing authority of Maharashtra State.

Personnel

The manufacturing and testing operation are carried out under the

supervision of expert technical staff duly approved by the licensing

authority.

For each section separate production supervisor, assistants are

employed which are trained to maintain higher standard of quality.

Premises

For manufacturing of Tablets, Syrup and powder Company has its

well-constructed premises. Manufacturing sections are adequate in size for

the present need of firm. Interior surface of the premises i.e. walls, flooring,

ceiling are smooth and free from cracks & permits easy cleaning. Premises

are well lightened and ventilated. Air conditioning system had been also

employed wherever necessary. Area for processing Rifampicin containing

formulating have been provided and thus care is taken to avoid cross

contaminating.
Storage area

The firm has provided separate areas for storage of raw material and

packaging material. Materials are orderly place in the storage room.

Sensitive materials are stored in A.C. rooms wherever necessary. Separate

areas have been provided for storage of finished products.

Equipments

All the manufacturing areas have been installed with proper

equipment and fair degree of automation. Most equipment is suitable for

their use and they are easy to clean and set. Operating conditions of the

equipment's and procedures are displayed at the site of installation.

Weighting instruments and measures are calibrated and records are

maintained.

Sanitations:

The manufacturing premises are maintained neat and orderly. Enough

plantations to reduce mince of dust surround the premises.

Starting material

An inventory of all the raw material and packaging material is made.

The storage areas are adequate in size and separation of material is done.

'Under Test' and then passed.

 The details of raw materials and packing materials are recorded for

their receipt and issues. All inward and outward entries of all raw materials

are done before these are issued for manufacturing. Also sample are stored

in quantitative and released for consumption only after the receipt of

satisfactory report from the A.C. Laboratory.

Manufacturing operations

All manufacturing operations are conducted under direct supervision

of expert production supervisions and other technical staff, approved by the

licensing authority. Proper tags/labels are pasted to mechanical

manufacturing equipment's during operations. The working personnel wear

clean factory uniforms. All the workers are provided with slippers.

Manufacturing personnel

There are about 70 workers out of which 40 male workers and

remaining are female workers. All the workers medically examined at the

time of their employment and periodically thereafter.

DOCUMENTS RELATING TO MANUFACTURING PROCEDURES

As company performs job work for the standard companies like Cipla

Novartis so these companies provides master formulae for all its proprietary

products. These gives details of manufacturing process, each step to be

followed precautions to be taken in the manufacture and controls to

exercised for half finished products.

BMR (Batch manufacturing Record)

BMR is prepared for each batch of the products manufacture. These

records include the details of name of the drug, batch no, yield obtained at

various stages of production, records of each step followed and details of

IPQC " tests & performed IPQC test on it.

To these records specimens of labels and samples are attached. These

records are maintained for specified period of time.

Labeling & Packing

All the labeling & packing material are handled by stores person.

There is a separate arrangement for storage of these materials is issued to the

packing dept. on requisition report. A finished product after testing by QC

for the quality of the product are sent for labeling and packaging labels of all

products meet the requirements of labeling & include prescribed details.

Q.A. department

Company has its own O.A. department, which undertakes the testing

of raw material, in process material, and finished product involving

chemical, instrumental and microbiological analysis. For the purpose the

dept. is equipped with enough instruments to meet the requirements such as

UV spectrophotometer, IR spectro, HPLC, KFR, etc.

Q.A. department is adequately staffed with competent persons

processing adequate qualification.

It prepares all testing procedures & stability studies.

The records of all the test performed and report issued is kept for

specified time. The lab premises are also suitable designed with separate

rooms with instruments microbiological analysis and controlled samples.

Animal testing so are not carried with in this O.A. lab for those

studies they send the samples in R & D lab of company.

Licenses
a) Own
b) By Loan License
c) Principle to Principle

• P. Loan license products are those for which a company manufacture's

the product of another company under the permission of license. It

just manufactures the product but the name on the pack is that of the

parent company.

• Principle-to-Principle means that the product is manufactured and raw

material is also purchased by this company and test basic principle is

of other company i.e. principle of other company is used and same

principle is followed.
 BIOSYNTH PHARMACEUTICALS PVT. LTD.

Syrup

Batch Production

Batch No. : LST 7011

Batch Size : 10000 Bottle

Mfg. Date : 7 July 2008

Use Before : 2 Year of mnf. date

 Biosynth Pharmaceuticals Pvt. Ltd.

Requisition Slip

The Store Incharge (R.M.)

Please issue the following for : Sudokof

Batch No. ; LST 7011

S.No. Ingredients Actual Qty. Reference

(in order of mixing) Used Number
1. Sucrose 500 gm
2. Sodium Benzoate 5 gm
3. Citric Acid 1.25 gm
4. Sodium Citrate 10 gm
5. Ammonium Chloride 30 gm
6. Colour Amarnath 0.2 gm
7. Flavour 1.25 ml
8. DJ water 0.5 – 1000 ml.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
Remark

1. Use face mask and rubber gloves at all time when handling the

materials.

2. Check and weight all ingredient before addition

Process

1. In a 500 litre capacity tank take 100 litre of DM water and dissolve

200 kg of sucrose and stirring continued for 2.30 hrs.

2. In a 10 litre container take 1 litre DM water and dissolve 400 gm 500l.

methyl paraben mix in step – 7

3. Take in a 15 l. Bucket 5 litre DM water and dissolve 2 kg of sodium

Benzoate with constant stripping and mix in sugar step no. 1

4. In a bucket take 2 litre purified water and dissolve 400 gm of citric

acid adding sugar syrup step 1 and fitter.

5. Add in Batch group -1 500 gm of sodium saccharin.

6. In a 10 litre capacity bucket take 2 liter purified water and dissolve

420 gm ephdrive HCL add in Batch group constant stirring.

7. In a 20 liter capacity bucket take 10 liter purified water dissolve 4.200

kg sodium citrate and add Batch syrup.

8. In a 50 liter tank take 30 l. purified water and dissolve 12.600 kg of

ammonium chloride add in bach group.

9. Add 80 gm of Col Amarnath.

10. Make up the volume of Batch syrup – 400 litre adjusted the pH of the

batch syrup 6-6.5.

Work

- Mixing

- Filtration

- Bottle washing

- Filling

- Cap cleaning

- Cap sealing

- Labelling pasting

- Final Packing
Mixing and Homogenisation

Mixing may be defined as the process in which two or more than two

components in a separate or roughly mixed condition are treated in such a

way so that each particle of any one ingredient lies as nearly as possible to

the adjacent particles of other ingredients or components.

Types of Mixtures

Mixtures may be classified as follows :

1. Positive mixtures

2. Negative mixtures

3. Neutral mixtures

Mechanism of Mixing

In all type of mixing is achieved by applying one or more of the

following mechanisms.

(i) Convective mixing : During convective mixing transfer of groups of

particles in bulk take place from one part of powder bed to another.

(ii) Shear mixing : During shear mixing. shear forces are created within the

mass of the material by using agitator am1 or a blast of air.

(iii) Diffusive mixing : During this mixing the materials are tilted so that the

gravitational forces cause the upper layers to slip and diffusion of individual

particles take place over newly developed Surfaces

Rate of Mixing

Generally speaking mixing is the process of achieving uniform

randomness which on subdivision to individual doses contains the correct

proportions of each component which depends on the amount of mixing

done. In the early stages of mixing, the rate of mixing is very fast because

the mixing particles change their path of circulation quickly and find

themselves in different environment whereas at the end of the process rate of

mixing reaches to almost zero because the particles do not find different

environment.

Liquid Mixing

Liquid mixing may be divided into following two subgroups:

(a) Mixing of liquids and liquids

(i) Mixing of two miscible liquids

(ii) Mixing of two immiscible liquids

(b) Mixing of liquids and solids

(i) Mixing of liquids and soluble solids

(ii) Mixing of liquids and insoluble solids.

(i) Mixing a liquids and soluble solids (Homogeneous, mix res e.g solutions)

In this case soluble solids are dissolved in a suitable liquid by means of

stirring. It is a physical change i.e. a soluble solid is converted to a solution)

(b) (ii) Mixing of liquids and insoluble solids (Heterogeneous mixtures e.g.

suspensions)

When insoluble solids are mixed with a vehicle a suspension is

produced which IS an unstable system. The ingredients of a suspension

separate out when allowed to stand for sometime.

Therefore to get a good suspension a suitable suspending agent should

be used. On small scale, suspensions may be prepared in a pestle and mortar.

A number of equipments e.g. shaker mixers, propeller mixers, turbine

mixers and paddle mixer are used for liquid mixing but out of these propeller

mixers are most widely used.

(i) Shaker mixers in these mixers, the material present in the containers is

agitated either by an oscillatory or by a rotary movement. The former is

applicable for small scale work whereas the latter is applicable for large

scale work i.e. for rotating the large vessels similarly as that of ball mills.

Shaker mixers have limited use in industries.

(ii) Propeller mixers Propeller mixers are the most widely used form of

mixers for liquids of low viscosity. They are not suitable for viscous liquids

like glycerin, liquid paraffin, castor oil etc. The size of the propeller is very

small as compared to the size of the container. It rotates at a very high speed
i.e. upto 8000 revolutions per minute due to which mixing are done in a

shor1 time.

Sometimes the high speed of the propeller may lead to undesirable

vortex formation and entrapment of air (once the air bubbles are entrapped

they are difficult to remove from the product which sometimes may lead to

air oxidation). This problem can be avoided in a number of ways as

described below:

(i) By attaching the propeller shaft off-set from the centre (a)

(ii) By mounting the propeller at an angle (b)

(iii) By entering the propeller shaft from the side of the vessel (c)

(iv) By using a push-pull propeller (d) in which two propellers of opposite

pitch are attached on the same shaft so that their rotary effects are in

the opposite directions and cancel each other.

(v) By using one or more baffles, which are generally vertical strips

attached to the sides of tl1e vessel (e)

or curved blades are attached (Fig. f). These mixers are distinguished from

propellers in that they are rotated at a lower speed than propellers and the

ratio of the impeller and container dian1cter is also low. The foffi1er

produces greater shear forces thal1 propellers therefore they are used for

mixing liquids of high viscosity and has a special application in the

preparation of emulsions.

(iv) Paddle mixers in some of the liquid mixers a number of paddles are used

as impellers which consist of flat blades attached to a vertical shaft and

rotate at a low speed of 100 r.p.m. or less the blades have a large surface

area in relation to the container in which they are employed which help them

to rotate close to the walls of the container and effectively mix the viscous

liquids or semi-solids. A variety of paddle mixers having different shapes

and sizes depending on the nature and viscosity of the product are available

for use in industries.

Filtration and Clarification

Filtration may be defined as the process in which sounds are separated

from liquids by means of a porous medium which retains the solids but

allows the liquid to pass through it and optically transparent liquid free from

insoluble solids colloidal hazes, or insoluble liquid drops is obtained.

The term clarification is used when the solid present in the liquid is

very small and they do not exceed 1.0 percent and filtrate is the required

product.

The suspension of solids and liquids to be filtered is known as feed or

slurry and the porous medium though which the slurry is forced to pass is

called filter medium the solids collected on the filter medium is referred to

as filter cake and clear liquid which passes through the filter is called filtrate.

When solids collected on the filter medium is the desired product then the

process is known as cake filtration. The mechanism of filtration is based on

two operations that is

(i) the flow of solids is resisted by the filter medium while the liquid is

allowed to pass.
(ii) as the filtration proceeds the retention of solids on the filter media goes

on increasing which acts as a secondary and sometimes more efficient

filtering medium.

Factors Affecting Rate of Filtration

The factors which affect the rate of tl1tration of any 1iquid is expressed by

Darey's law which is stated as under :

dV KA 6P
dt ηl

where V = volume of filtrate

t = time of fi1tration

K = constant for the filter medium and fitter cake.

A = area of fitter medium

∆ P = pressure difference above the fitter medium and below the fitter

medium i.e. on the filtrate

η = viscosity of the filtrate.

l = thickness of the filter bed i.e. thickness of the filter cake and filter

medium

The above law represents the rate of flow through the capillaries of

the filter medium and filter cake. From the above equation it is clear that the
rate or filtration depends upon a number of factors and not only the liquid

which is undergoing filtration.

The factors which govern the rate or filtration are as Follows:

1. Area of Filter Surface

Rate of filtration is directly proportional to the area of fitter surface.

Greater the filtering surface greater will be the rate of filtration e.g. with the

use of pleated filter paper filtration is increased.

2. Particle Size of the Solids to be Removed

Rate of filtration is directly propol1ional to the particle size of the

solids 10 be removed.

3. Pore Size of the Filter Media

Rate of filtration is directly proportional to the pore size of the filter

media.

4. The Resistance of the Filter Cake and Filter Media

The rate of flow will be greatest at the beginning of the process

because there is minimum resistance but as the process proceeds the filter

cake is fonl1cd which goes on increasing and adding thickness to the cake

which slows down the rate of filtration but this fake also acts as a secondary

filter medium.
5. Viscosity of the Liquid to be filtered

The rate of filtration is inversely proportional to the viscosity of the liquid to

be filtered, Liquids with low viscosity get filtered quickly whereas thick

liquids get filtered slowly. The rate of filtration of such liquids can be

increased by applying pressure on the viscous liquids or by increasing the

temperature of liquid to be filtered

6. Temperature

Increased temperature reduces the viscosity of thick liquids such as

syrup, glycerin, liquid paraffin etc. thus they, can be filtered quickly.

In some cases filter presses are so constructed that they can be

maintained at high temperatures through which viscous liquids are to be

filtered.

Pressure Difference across the Filter

The rate of filtration is directly proportional to the pressure difference

across the filter bed. The rate of filtration can be increased by increasing the

pressure on the liquid to be filtered (cake filtration) or by reducing the

pressure under the filter media i.e. in the receiver (vacuum filtration).
Filter Media

The surface or medium upon which solids are retained the process of

filtration is known as filter media. An ideal filter media should have the

following properties:

(i) It should be chemically inert.

(ii) It should have high retention power for the solids but should allow the

maximum passage of the liquids.

(iii) It should have sufficient mechanical strength to withstand filtration

pressure.

(iv) It should absorb negligible amounts of dissolved material.

While filtering liquids containing slimy compressible materials the

filter media soon get clogged and it becomes necessary to add a material

which will check this problem such type of substances are known as filter

aids. Filter aids may be defined as the substances which when added to the

liquid to be filtered reduce the resistance of the filter cake and increase the

filtration. These substances form a porous non-compressible cake which can

retain the solid particles but allow the liquid to flow through it. A

concentration of 0.1 to 0.5% of filter aid is added to the preparation before

filtration. They may be added directly to the suspension to be filtered or a

suspension of filter aid is first prepared in a suitable liquid which is then

added to the liquid to be filtered.

An ideal filter aid should have the following characteristics:

(i) It should be chemically inert.

I(ii) It should have low specific gravity.

(iii) It should be insoluble in the liquid to be filtered.

(iv) It should form a porous cake.

(v) It should be readily recoverable from the liquid.

The substances which are used as filter aids include kieselguhr, talc,

charcoal, asbestos, paper pulp, kaolin, chalk, magnesium carbonate and

bentonite.
 Type of Filter

1. Filter Paper

2. Cotton wool

3. Glass wool

4. Asbestor

5. Sintered glass

6. Membrain Fitter

7. Fitter leaf
 TABLET

BATCH PRODUCTION

Batch No. : BST 9010

Batch Size : 100000 Tablet

Mfg. date : 15 July 2008

Use before : 15 July 2010

 REQUISITION SLIP

Please issue the following for M vit. tablet

Batch No. 857/9010

S.No. Ingredient Actual Qty. used

1. Methylcobalamine 750 mg
2. Vitamin A 2500 IU
3. Vitamin E 25 mg
4. Sodium Selenite 75 mg
5. Zinc sulphate monohydrate 7.5 mg
6. Folic acid 500 mg
 Tablets are solid pharmaceutical dosage forms containing with or

without suitable diluents and prepared either by compression or molding

method.

Large-scale production methods used for there preparation require the

presence of other materials in addition to active ingredients. Additives also

may be included in the formulation to facilitate handling, enhances the

physical appearance; improve stability and aid in the delivery of the drug to

blood stream after administrations.

Although tablets are frequently discoid in shape they also may be

round, oval, oblong, cylindrical or triangular. They are divided in to two

general classes, whether they are made by compression or molding.

Compressed tablets usually are prepared by large-scale production methods

while molded tablets generally involved small-scale operation.

There exist different types of tablets, which are as follows:

a) Compressed tablets (CT)

b) Sugar Coated Tablet (CST)

c) Film Coated Tablet (FCT)

d) Enteric Coated Tablet (ECT)

e) Multiple Compressed Tablet (MCT)

f) Controlled Release Tablets

g) Tablets for Solution \

h) Effervescent tablets

i) Compressed Suppositories or Inserts

j) Buccal and Sublingual Tablet

 MANUFACTURING AREA

Tray W.I.P. Blendiang Granulation II

Dryer

Cubicle Cubicle Tablet Granulation

Coating 1 2 Filling & 1

Documentation
Cubicle Cubicle Washing
Polishing
3 4 Room
Room
GRANULATION

Equipment

1. Fluidized bed dryer

Make Indogerman

Capacity 120 Kg.

HP/KW 15/112

Description It is used for drying granules

2. Multimill

Make Anchor Mark

Sieve Used are of size 8mm, 24mm, 2mm, 1 mm, 0.5mm Description: As

the name suggest it is used for multiple purpose such as dry blending and

granulation. A sieve is placed around the blade arrangement of impact and

knives can be made as per requirement. Knives are forward for granules

where as impacts for powder. Gears are provided at the top of the machine

so as to adjust the speed of machine.

3. Planetary Mixer

Make Anchor Mark

liP 11.5 Volts: 415 V

Capacity 350 Litres

Description This is used for mixing i.e. either dry or wet mixing.
Dry mix

It is used for mixing of active constituent with other dry powder

constituents.

Wet Mix

It is used for mixing active constituent with binding agent so from the wet

mass which further undergo milling process.

4. Sifter

Make : Anchork Mark

Description: It is used for sieving purpose which can be done with the help

of various no. of sieves. For example 16, 20,40.

5. Blender

Make : Marvald

Capacity : 50 Kg.

Description: It is made up of stainless steel, In this blender first the granules

are loaded for mixing of active ingredients. Then lubricant is added in

specified amount for 12-15 minutes or as per specification, Speed varies

with adapted procedure.

6. Steam Jacketed Kettle

Make : Anchor Mark

Description: This is used for making starch paste.

7. Tray dryer

Make : Anchor Engineering

Capacity : 18' Trays

Description: It is used for drying of granules. It consists of huge trolleys

which are loaded with trays containing granules to be dried. There is heater

through which incoming air is heated and circulated with fan. The drying

time is usually 8 hours.

1. W.I.P. Area:

All the work in progress material is stored here.

 MANUFACTURING PROCESS

Weighing

All materials are weighed to the nearest accuracy by the worker under the

supervision of a Product Executive. The label states the

- Product name

- Name of the material

- Weight in Kg

- Sign of the worker

- Sign of the Supervisor

All these are fixed on the pack of each material and sent to the Production

department.

Size Reduction (communication) and Sieving

The solid raw material is comminuted if required to suitable size and sieved

to get required size of materials.

Dry Mixing

Dry mixing is carried out in "mass mixer". A mass mixer gives thorough

mixing of the solids. The speed of the mass mixer can be regulated. The

mass mixer is provided with a safety switch due to which, when the lid is

opened the mixer steps and accidents are prevented.

Preparation of Starch Paste

The preparation of starch paste is carried out in a steam pan. Water is kept

for boiling and in another vessel slurry of starch is prepared. When the water

starts boiling the slurry is added with continuous stirring to obtain the starch

paste, the formation of lumps is to be avoided using a granulating agent.

Granulation

Get granulation process involves the following steps

1. Weighing of ingredients

2. Sifting

3. Mixing

4. Wet mass milling

5. Drying

6. Size reduction

7. Blending

Dry granulation process involves similar steps except for addition of the

binder.

Direct Compression Method is employed for a few crystalline substances.

Granulation is carried out in Mass mixer. The starch paste is added to

previously mixed solid material and mixed properly and a mass suitable for

granulation is formed.

Passing through Multimill

The wet mass formed in the Mass mixer is passed through the multimill. The

Knives of the multimill help in size reduction and the sieve provided at the

bottom of the mill helps in the formation of granules of the required size.

Drying and Sifting

The drying of the wet granules obtained from the multimill is done in the

fluidized bed dryer for a specified time. The FBD gives uniform drying of

the granules. The dried granules are passed through the sieves to obtain

granules of required mesh size.

Lubrication and Compression

The dried and sieved granules are lubricated with steamates in a double cone

blender. These lubricated granules are labeled as "ready for Compression".

These granules are taken to the compression section where they are

compressed into tablets of required weights and hardness.

In the compression machine different knobs are provided for adjustment of

weight, thickness and hardness of tablets. Both upper and lower punches are

provided. Then the compressed tablets are periodically tested for hardness,
weight, DT, etc The compressed tablets are then taken to the coating section

for coating or casting if necessary.

Tablet Coating

Tablet coating is carried out in a coating pan. This pan is made up of

stainless .steel provided with adequate mouth opening and depth. Easy

mounting arrangements for change over are provided. Coating pans are

provided with tilting arrangements for quick charge and discharge. Hot air

blower is provided to feed hot air at temperature of 40-80 deg C controlled

by thermostats. Quantity of hot air can be controlled by dampers.

Coating solution is applied to the tablets by spraying the material into

the rotating tablet bed. Peristaltic spray pump is proved. Speed of the

rotation of the pan is adjustable generally up to 16 rpm.

- Sugar coating is normally done in order to

- Mask the colour, odour, taste of the drug i.e. to increase the

palatability.

- To control the release of drugs from the tablets.

- Sugar Coating involves the following stages

a. Seal coating

It is mainly done to prevent moisture penetration into the tablet core.

Mainly shellac is employed.

b. Subcoating

It is applied to round the edges and to build up the size of the tablet.

This consists of alternately applying the sticky binder solution followed by

dusting of subcoating powders and then drying.

c. Syrup coating

It is done to cover and fill the imperfections on the tablet surface and

to impart the desired colour to the tablet. The first syrup coat usually

contains some suspended powder called Grossing Syrup. Dilute solutions of

colourants are added.

d. Polishinq

The desired luster is obtained as a final step in the sugar coating

process.

Coating solution composition

• For enteric coating

• Methylene chloride

• MethanollP

• Cellulose acetate phthalate

• PEG 6000 IP

• Lake of Tartrazine

• Titanium dioxide IP
• Propylene glycol

For film coating

• Methylene chloride

• Propylene glycol

• Isopropyl alcohol

• PEG 6000 US NF

• Lake of Tartrazine

• Talc

• Hydroxy methyl cellulose

• Titanium dioxide

GMP TO BE FOLLOWED IN THE TABLET DEPARTMENT

• Mask and gloves are to be used with proper training.

• Annual medical checkup.

• Quality inside the dept. should be built up at ails tages.

• Humidity maintained in the area.

• Positive pressure maintained in the area.

• Region should be fire proof.

• Separate rooms should be available for mfg. of different products.

• Machinery should be properly maintained.

PRODUCTOIN RECORD

The following points are noted down while production of tablets is in

process.

• Name of product

• Batch no.

• Batch size

• Weight of lubricated granules

• Punch size

• No. of punches

• Started on

• Weight of 20 tablets

• Average weight of 20 tablets

• Hardness (Kg/sq.cm)

IN PROCESS QUALITY CONTROL TESTS

• Friability Dissolution

• Hardness Weight variation

• Disintegration Content variation

TEST FOR TABLETS

1. Friability

2. Disintegration

3. Dissolution

4. Hardness

5. Uniformity of weight

6. Thickness & width and length.

TEST FOR CAPSULES

1. Content uniformity

2. Disintegration

3. Seal length

Evaluation of Tablets or Standardization of Tablets

The following standards or quality control tests are carried out on

compressed tablets.

1. Diameter size and shape.

2. Uniformity of weight.

3. Thickness.

4. Hardness.

5. Friability.
6. Percentage of medicament. Y

7. Rate of disintegration.

1. Diameter Size and Shape

The diameter size and shape of tablets depends on the die and punches

selected for making the tablets. The tablets of various sizes and shapes are

prepared but generally they are circular with either flat or biconvex faces.

2. Uniformity of Weight :

It is desirable that all the tablets of a particular batch should be uniform in

weight. If any weight variation is there, that should fall within the prescribed

limits (generally ± 10% for tablets weighing 120 mg. or less, ± 7.5% for

tablets weighing 120 mg to 300 mg and ± 5% for tablets weighing more than

300 mg). The test is considered correct if not more than two tablets fall

outside this range if 20 tablets are taken for the test and not more than one

tablet falls outside this range if only ten tablets are taken for the test. The

difference of weight in tablets can lead to variation in doses. Therefore all

the tablets of a batch must conform to this test. For carrying out, this test

generally 20 tablets at random are taken and weighed. The average weight is

calculated, then each tablet is weighed individually and weight noted. The

weights of individual tablets are then compared with the average weight
already calculated and see that not more than two tablets fall outside the

range. This test is repeated after short intervals of time to ensure that tablets

of required weight are produced.

3. Thickness

The thickness of a tablet can vary without any change in its weight. This is

generally due to the difference of density of granules, pressure applied for

compression and the speed of compression. The thickness of a tablet can be

determined with the help of micrometer calipers. The thickness variation

limits allowed are ± 5% of the size of the tablet. The variation in thickness

leads to counting and packing problem.

4. Hardness

The hardness of tablet depends on the weight of the material used,

space between the upper and lower punches at the time of compression and

pressure applied during compression. The hardness also depends on the

nature and quantity of excipients used during formulation.

If the finished tablet is" too hard, it may not disintegrate in the

required period of time and if the tablet is too soft it may not withstand the

handling during packing and transporting. Therefore it is very necessary to

check the hardness of tablets when they are being compressed and pressure

adjusted accordingly on the tablet machine.

 Tablet hardness can roughly be determined by holding the tablet in

between the fingers of the hand and throwing it lightly on the floor, if it does

not break it indicates that proper hardness has been obtained. A number of

hardness testers are used for determining the tablet hardness but Monsanto

hardness testers and Pfizer hardness testers are commonly used.

(a) Monsanto Hardness Tester

It is a small, portable hardness tester which was manufactured and

introduced by Monsanto Chemical Company.

It consists of a spring which can be compressed by moving the screw knob

forward.

Fig. 14.9 Monsanto tablet hardness tester

The tablet to be tested is held between a fixed and a moving jaw and reading

of the indicator adjusted to zero. The force applied to the edge of the tablet is

gradually increased by moving the screw knob forward until the tablet

breaks. The reading is noted from the scale which indicates the pressure

required in kg or lb to break the tablet. Hardness of 4 kg is considered

suitable for handling the tablets. Hardness of 6 kg or more will produce

tablets of highly compact nature.

(b) Pfizer Tablet Hardness Tester

Fig. 14.10 Pfizer tablet hardness tester

It is another instrument used for testing the hardness of a tablet. It works on

the principle of a plier and is similar in shape to that of a plier. It is fitted

with a dial. The tablet under test is held vertically in between the jaws which

are pressed with hand until the tablet breaks. The reading is noted from the

needle of the pressure dial which may be expressed in kilograms or pounds

of force.

5. Friability

Friability test is performed to evaluate the ability of the tablets to withstand

abrasion in packing, handling and transporting. The instrument used for this

test is known as 'Friability Test Apparatus' or 'Friabilator'. It consists of a

plastic chamber which is divided into two parts and revolves at a speed of 25
r.p.m. A number of tablets are weighed and placed in the tumbling chamber

which is rotated for four minutes or for 100 revolutions. During each

revolution the tablets fall from a distance of six inches to undergo shock.

After 100 revolutions the tablets are again weighed and the loss in weight

indicates the friability. The acceptable limits of weight loss should not be

more than 0.8 per cent.

Fig. Fibrialator

6. Percentage of Medicament

This test is perfoffi1ed to ensure that every tablet, coated or uncoated must

contain the stated amount of medicaments within the prescribed limits. A

number of tablets from a batch are selected at random and assay procedures
are carried out according to the monographs given in the official books. The

results obtained must be within the prescribed percentage limits.

7. Rate of Disintegration

The disintegration test is perfoffi1ed to find out that within how much time

the tablet disintegrates. This test is very important and necessary for all the

tablets, coated or uncoated to be swallowed because the dissolution rate

depends upon the time of disintegration which ultimately affects the rate of

absorption of drugs.

The apparatus used for this test is known as disintegration test apparatus.

This apparatus consists of a glass or plastic tube which is open at one end

and the other end is fitted with a rust proof No. 10 mesh sieve.

Fig. 14.12 (A) Tablet disintegration test apparatus

The tube is suspended in a bath of water or suitable liquid which is

thermostatically maintained at a temperature of 37°C. The tube is allowed to

move up and down at a constant rate i.e. 30 times per minute through a

distance of 75 mm. The volume of the liquid and distance of movement is

adjusted in such a way that at the highest point the mesh screen just breaks

the surface of the liquid to give a turbulent movement to the tablets and at

the lowest point the mesh screen remains about 2.5 cm. above the bottom of

the container.

About five tablets are placed in the tube alongwith a plastic disk over the

tablets unless otherwise stated in the monograph. The plastic disk does not

allow the tablets to float and imparts a slight pressure on the tablets. The

tube is allowed to move up and down and disintegration time noted when all

the tablets have passed through the sieve. This time should comply with the

time stated in the monograph for that tablet. The test fails if all the tablets do

not pass through the sieve within specified time. Generally the disintegration

time for uncoated tablets is 30 minutes and for coated tablets one hour.

8. Dissolution Test

The rate of dissolution of a solid drug plays an important role in the

absorption and physiological availability of the drug in the blood stream.

Therefore determination of dissolution rate of any solid drug is very

necessary. For this purpose there are a number of tests available in the
literature but none is official. This test is performed for tablets and capsules

when stated in the individual drug monograph.

The apparatus for dissolution test consists of (i) a cylindrical stainless steel

basket which is attached to the end of the stirrer shaft (ii) a l(xx) ml vessel

made of glass or other inert, transparent material fitted with a cover having

four holes, one for the shaft of the stirrer second for placing the thermometer

and remaining two for removing the samples (iii) a variable speed motor

driven stirrer which can rotate at a speed of 25-150 revolutions per minute

(iv) a suitable thermostatically controlled water bath to maintain the

temperature of the dissolution medium at a temperature of 37°C :t:0.5°C.

For performing the test a suitable volume of dissolution medium like

distilled water, hydrochloric acid or phosphate buffer at a pH of 7.3 as stated

in the individual monograph is filled in the glass vessel which is submerged

in the water bath maintained at 37°C. The tablet or capsule to be tested is

introduced in the basket and fitted in position. The motor is started and its

revolutions adjusted according to monograph. The samples are withdrawn at

specified intervals and filtered immediately through a suitable filter medium.

Generally 5 ml sample solution is withdrawn each time which is replaced

varying speed stirring motor with 5 ml of medium at 37°C in order to

maintain a constant volume in the vessel. The samples are tested by

chemical analysis for proportion of drug dissolved which should meet the

requirements as stated in the monograph.

Fig. 14.3 Dissolution test apparatus

BLISTER PACKING MACHINE

• Mfg. By : Pharmapack -240

• Speed: 96 cuts/min

• Parts: Blister forming roller -BRF

• Pressure forming roller -PRF

• Batch code printing unit -BCPU

• Gude track -GT

• Channel

• Punching tool I cutter

• Sensor bulb

It has a contact heating system and heats the polyvinyl chloride films that

are placed on the machine. This is done by the controlled heating of the PVC

film by contact with a heated roller.

Advantages

Controlled temperature of film between 130 -150 deg C.

Uniform heating causes uniform blister formation.
This eliminates film distortion.
Superior blister quality at all speeds.
Blister formation at lower temperature improves film barrier properties.
Improved GMP practices.
Operational ease.
Flow Chart for Q.A. Department
Flow chart of R.M.I.P.M.
Can be used for

Tablets
Dragees
Capsules
Soft gelatin capsules
Packaging materials

Base film: PVC (opaque I transparent)

Thermoformable and nontoxic

QUALITY ASSURANCE

It is the heart of any pharmaceutical industry.

Quality Assurance: It is define as All those planned & systematic ac

necessary to provide confidence that a product or service will satisfy

requirement for quality. .

Quality control: It is totality of feature & characteristic of a product that be,

its ability to satisfy stated or implied needs.

There are three division of quality control.

1. Chemical laboratory

2. Instrumental laboratory

3. Microbiological laboratory
1. CHEMICAL LABORATORY:

The chemical tests are carried out in this laboratory. The reagents, chemical

etc. are kept in this area. The official books are also present in this area.

2. INSTRUMENTAL LABORATORY:

There are instrument I & instrument II rooms are present. The various

instruments are present in this area. The SOP's along with instruments are

there.

3. MICROBIOLOGICAL LABORATORY:

The microbiological assay & other microbiological tests are carried

this area. The entry is prohibited. It is aseptic area. The culture are made

assay are carried out laminar airflow is also present which consist of HEPA

filter to maintain area aseptic.

IPQC

The quality control department is carried out in process quality control

during the actual manufacturing process.

Instrument used in QC dept.

1) Tablet friability Apparatus

2) Disintegration Apparatus
3) Dissolution Apparatus
4) Centrifuge machine
5) U. V. visible spectrophotometer
6) Photo flurometer
7) Cyclomixer
8) Magnetic stirrer
9) pH meter
10) Melting point & Boiling point determination apparatus.
11) Karl fischer automatic titrator
12) Electronic balance (Digital)
13) Hardness tester (Monsanto)
14) Pharma test (For Hardness, Diameter & Thickness)
15) Vernier calliper
16) Oven
17) Furnance
18) Autoclave
19) Refrigerator
20) Incubator
21) Polarimeter
22) TLC
23) HEPA filter
24) Electronics shaker
25) U. V. Cabinet
26) Sonometer
27) Brook field Viscometer
28) Leak test Apparatus
Functions of quality control department:

1) To carry out tests of raw material.

2) To perform IPQC actual manufacturing process.
3) To check cleanness.
4) To observe whether GMP is followed or not.
5) To provide BMR to production dept. on requisition.
6) To maintain records of tests perform in Q.C. dept.
7) To issue passing of finished goods.
8) To check quality of stored and finished products after definite time.
 CONCLUSION

Hypodermic tablets are soft, readily soluble tablets which are made in
a tablet triturate mold. They are used for preparing solutions to be injected,
therefore in selecting the materials used for preparing the hypodermic tablets
care must be taken that they should be completely and readily soluble and no
insoluble particle should be present. They should be free from bacterial
contamination and proper precautions should be taken during molding
regarding contamination and cleanliness.
Since the solutions prepared from hypothermic tablets are rarely
sterile and a number of sterile parenteral solutions are now available
therefore the use of hypodermic tablets for preparing solutions for injections
is being discouraged.
These tablets are prepared for providing an accurate and convenient
quantity of a potent drug that can be incorporated readily in compounding
other dosage forms, e.g., liquids, powders or capsules, thus eliminating the
necessity of weighing small quantities of potent substances. These tablets
are solely designed to provide a convenient quantity for extemporaneous
compounding and should never be dispensed for administration as a dosage
form because sometimes they contain very potent drugs which may prove
fatal.
Syrups are the sweet, VISCOUS, concentrated aqueous solutions of
sucrose or other sugars in water or any other suitable aqueous vehicle. When
purified water alone is used in making the solution of sucrose the
preparation is known as syrup or simple syrup. When the preparation
contains some medicinal substance it is known as medicated syrup. When
the syrup does not contain any medicament but contains various aromatic or
pleasantly flavoured substances are known as flavouring syrups. They are
used for masking the disagreeable taste of bitter or saline drugs. They are
also used as vehicles or flavours for extemporaneous preparations.
In addition to sucrose, certain other polyols, such as glycerin, sorbitol
or other polyhydric alcohols may be added in small amounts to retard
crystallization of sucrose or to increase the solubility of other added
ingredient.
In the manufacture of syrups the sucrose and purified water free from
foreign substances should be selected and clean containers must be used to
avoid contamination during preparation: Dilute solutions of sucrose support
mold, yeast and other microbial growth whereas the growth of such
microorganisms is usually retarded when the concentration of sucrose is
65% weight by weight or more but a saturated solution may lead to
crystallization of sucrose.