biosynth
TRANSCRIPT
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, GwaliorFor the fulfillment of M.Sc. Industrial Chemistry
Session
2007-2009
Under Supervision of Submitted toMr. S.C. Gupta Dr. Shadhna ShrivastavaProduction Manager H.O.D. Industrial Chemistry
Submitted byRaushan Kumar
Department of Industrial ChemistrySMS 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(in order of mixing)
Actual Qty. Used
Reference Number
1. Sucrose 500 gm2. Sodium Benzoate 5 gm3. Citric Acid 1.25 gm4. Sodium Citrate 10 gm5. Ammonium Chloride 30 gm6. Colour Amarnath 0.2 gm7. Flavour 1.25 ml8. 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 6Pdt l
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
= 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
Dryer
W.I.P. Blendiang Granulation II
Coating
Cubicle
1
Cubicle
2
Tablet
Filling &
Polishing
Room
Documentation
Granulation
1
Cubicle
3
Cubicle
4
Washing
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.
Flo
w C
har
t fo
r Q
.A. D
epar
tmen
t
Flo
w c
har
t 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.