vijay ostwal training report
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CHAPTER 1
AN
INTRODUCTION
AND LAYOUT
1
INTRODUCTION
JYOTI REMEDIES is a research & development driven, pharmaceutical manufacturing
group of companies .Our manufacturing location in India- is at Saproon, the industrial
Hub of Himachal Pradesh State of India.
Our multidimensional Ethical product range includes: Capsules, Tablets. We strictly
follow WHO GMP norms for manufacturing process for all our products. Our Contract
manufacturing of products provides great value to major marketing companies of India.
We are truly committed to alleviate human suffering in the most possible ethical manner.
JYOTI REMEDIES commitment to serve the mankind predominantly with an objective
to provide top quality and cost effective products. Mr. Kuriakose initiated pharmaceutical
business activities in 1986 and started manufacturing process by setting up a full fledged
drug formulation unit in Kerala in the year 1993 Under-cited were the primary
objectives at the start of Jyoti Remedies
Consistency in maintaining high quality drugs
Constantly expanding products portfolio
One time product delivery
State of the art manufacturing facilities
Conforming to prevalent and demanding international standards
Today Jyoti Remedies commands a reputation of upcoming pharmaceutical thespian in
the pharma world with 4 Divisions.The group of concerns are:
Ce-Biotec (P) Ltd.
Ce-Chem Formulations
Jupiter Drugs
2
3
4
CHAPTER 2
ORGANISATION
5
MANAGING BODY
Board of Directors:
Managing Director (M.D.) : Mr. C.P. Kuriakose & Mr. Sudhir Sharma
Others:
Production Incharge : Mr. Lal Singh
Q.C. Incharge : Mr. Bhaskar Patel
Store Incharge : Mr. Manoj Sharma
Maintenance Incharge : Mr. Azad Ali
Marketing Incharge : Mr. Ajay Sharma
Computer Operator : Miss Kalpna
Corporate Office : Ce-Biotec (P) Ltd.
Ce Pe Towers, tana, P.B. No.23
Irinjalakuda, Trissus 680101
Kerala, India Tel. No. 0480-2825605
Factory at : Jyoti Remedies (P) Ltd.
Vill. Kailer, Subhathu road
P.O. saproon, Solan India 173211
Tel. No. 0192-228378, 09805559011
6
GMP FOR PREMISES AND MATERIALSTABLE 2 SPECIFIC REQUIREMENTS OF PLANT & EQUIPMENT:
S.no
Section
Area (minimum)
For basic installation For ancillary area
1: Tablets 60 Sq. m (Uncoated)
30 Sq. m (Coated)
20 Sq. m
10 Sq. m
2: Capsules 25 Sq. m 10 Sq. m
3: Repacking of drugs & pharmaceuticals
35 Sq. m
1 General requirements:-
1.1) Location and surroundings: Jyoti Remedies Pvt. Ltd. is situated in Vill. Kailer,
Subhathu road P.O. saproon, SolanThe location of this factory is such that it
avoids risk of contamination from external environment including open sewage,
drain, public lavatory or any factory which produces disagreeable or obnoxious
odour, fumes, and smoke, chemical or biological emission.
1.2) Building and premises: Factory’s building conformed to the conditions laid down
in the factories act, 1948. The premises used for manufacturing, processing,
warehousing, packaging labeling and testing purposes is compatible with other
drug manufacturing operation. It has adequate working area which allow orderly
and logical placement of equipment, materials and movement of personnel so as
to avoid the risk of mix up, contamination and cross contamination.
2 Ware housing area:
It has adequate area with proper racks, bins and platforms for the storage and
warehousing of all materials and products, machine and equipment parts etc.
Adequate fire protection measures are also present.
7
3 Production area:
In Jyoti Remedies, this area is designed to allow the production preferably.
Working and in process space is adequate to permit orderly and logical
positioning of equipment and materials and movement of personnel to avoid cross
contamination.
4 Ancillary area:
Rest and refreshment rooms are separate from other areas and do not lead directly
to the manufacturing and storage area. Separate toilets for males and females are
provided.
5 Personnel:
The manufacturing is conducted under the direct supervision of Mr Lal Singh.
(Manufacturing Incharge). The company has very well qualified and competent
technical staff.
6 Health, clothing and sanitation of workers:
Prior to employment all personnel’s undergo medical examination. They wear
clean body covering. Smoking, eating, drinking, chewing or keeping plants, food,
drink and personnel medicines are not permitted in production laboratory storage
and other areas.
7 Precaution against mix-up and cross contamination:
Recalled or rejected material and other material that are not to be processed or
recovered are kept in segregated, enclosed areas.
8 Sanitation in manufacturing premises:
Manufacturing premises of Jyoti Remedies is cleaned and maintained in an
orderly manner. It is free from accumulated waste, dust, debris and other material.
9 Raw materials:
All raw materials are purchased from approved sources. There are adequate
separate areas for material under test, approved and rejected. All the containers of
raw materials are placed on the raised platforms, racks.
8
10 Equipment:
All the equipments are located designed, constructed, adapted and maintained to
suit the operation. Balances and other measuring equipments are calibrated and
checked on a periodical basis.
11 Labels and other printed materials:
The label carries all the prescribed detail about the product. All containers and
equipment bears appropriate label. Different colour coded label are used to
indicate the status of the product.
Example:
Under test Yellow
Passed Green
Rejected Red
12 Master formula record:
Jyoti Remedies has master formula records relating to all manufacturing
procedure for each product and batch size to be manufactured.
13 Batch processing records:
These records are based on the relevant parts of the currently approved master
formula.
9
JYOTI REMEDIES
Vill.-Kailer, Subhathu road P.O. saproon, Solan
MANUFACTURING RECORD
(As Per Schedule U & GMP)
Name of Product…………………..Master Formula Ref. …………………………
Size…………………..B.No……………….S.No…… ………………………………
Room Temp……………R.H………….Date Of Commencement……………………
INGREDIENTS Label Claim
C.R. No. Qty. Req. Qty. Used Stock Ledger
Kg. gm. Kg. gm.
Active Ingredients
FILLERS
Starch I.P.
Di Cal. Phos. I.P.
Lactose I.P.
Date of Mixing ……………… Duration……….Hrs. Total Wt =………………..
PASTE (Binders)
Starch
Gelatin
Sod. Benzoate
Colour
Date Of Granulation……………………….. Dried at =………………………………
Time Required…………………………… Wt. Of Dried Granules……………………
10
LUBRICANTS
Starch (Dried)
Talcum
Mag. Stearate
TOTAL Wt.=
Weight of Lubricated Granules =_______________________Kg
Added Lubricated Granules of previous
Batch No. =_______________________Kg
(wt. Per tablet______________mg)
Total wt. Of Lubricated Granules ready for
Compression = Kg
COMPRESSION:
Date of Compression_____________
Weight of One tab. Should be_______________mg
Punch size Diameter_____________ Width_______________ Length___________
Appearance____________________________ Surface________________________
Scored___________________________ Embossed__________________________
Hardness__________________Kg/cm2 Disintegration Time____________________
Friability_______________% Weight of 20 tablets______________gm
Average weight per tablet______________
Permissible limit of wt. Variation____________
Individual wt. Of 20 tablets in mgs.
11
PACKINGS
Packing Material Required:
PARTICULARS QTY. USED
DESTROYED TOTAL STOCK LEDGER
Boxes (Plastic)
Pouch
Labels
Strips Qty.
Cartoons
Catch Cover
Printed Particulars On Label Batch No._________________
Rate Strip (per 10 tabs) =_________________
Mfg. Date__________________ Exp. Date____________________
Date______________
No. of Box Qty. per Box Total Tablets
Samples: For Analysis :
12
For Quality Control Deptt. :
________________________
Total =
________________________
Percentage Yield
Date of Completion ____________________
Quality Control:
Sample Tested by______________________________________________________
Analytical Report No._____________________ Date__________________________
Result: Passes/Fails
Date of Release For Warehouse___________________________________________
_____________________________________________________________________
Quantity Released To Warehouse:
PACKING NO. OF BOXES STOCK LEDGER
Date Of Completion:___________________
Signature Assistant Mfg. Chemist Signature Analytical Chemist
Signature Mfg. Chemist In-charge_______________________
13
In-Process Quality Control :
Hardness of tablet________________Kg/cm2 Friability____________________
Disintegration Time_______________ Wt. Of 20 Tablets _______________gm.
Average Wt. Per Tablet_________________ Claim_______________________
Permissible Limit Of Wt._______________
Individual Wt. Of 20 Tablets in mgs.
Wt. Of 20 Tablets at intervals of 30 Minutes in gm.
1: 2: 3: 4:
5: 6: 7: 8:
9: 10: 11: 12:
13: 14: 15: 16:
17: 18: 19: 20:
21: 22: 23: 24:
25: 26: 27: 28:
29: 30: 31: 32:
Signature of Analytical Chemist
14
CHAPTER 3
TABLET SECTION
15
INTRODUCTION
Tablets are obtained by compression of uniform volumes of powders or granules by
applying high pressures and using punches and dies. The particles to be compressed
consists of one or more medicaments, with or without auxiliary substances such as
diluents, binders, disintegrating agents, lubricants, glidants and substances capable of
modifying the behavior of the medicaments in the digestive tract. Such substances must
be innocuous and therapeutically inert in the quantities present. It is possible to
manufacture tablets in a wide range of shape, size and weight which depends on the
amount of medicament and the mode of administration. but they are also available in
special shapes like round, oval, oblong, cylindrical, square, triangular etc.
Official tablets are defined as circular discs with either flat or convex faces. The tablets
provide an accurate, stable dose of drug with the necessary physical and chemical
properties for the requirement of duration and intensity of therapeutic action.
Defination of Tablet According To I P – 1996
Tablets are solid dosage form each containing a unit dose of one or more medicaments.
They are intended for oral administration.
Defination of Tablet According to USP – 23rd Edition:-
Tablets may be defined as the solid unit dosage form of medicament(s) with or without
suitable diluents and prepared either by molding or by compression.
Manufacturing of Tablet:-
There are different processes, which are involved in the manufacturing of tablet. These
are as follows:-
Weighing section
Granulation section
Drying section
Compression section
In Process Quality control
Coating section
Packaging section
16
MIXING
In this process, the raw materials (Medicaments + fillers) are taken from raw material
store room and then weigh accurately as per master card in the balance room.
These raw materials are then sifted in accordance with a specific no. of sieves. The sieved
raw materials are then mixed uniformly by Ribbon Blender (Sigma mass mixer). This
blender has a capacity of 100 kg. It is made up of stainless steel covered at top according
to the GMP.
Preparation of Binder solution (Starch and Gelatin Paste):-
a) The hot gelatin solution of specified quantity was prepared using D.M. water.
b) Suitable coloring agents were dissolved in small quantity of water and then
incorporated in hot gelatin solution with stirring until it mixes uniformly.
c) Now prepare starch solution of specified quantity in cold water and then mixed
gradually in small amounts in hot gelatin solution with constant stirring.
After appropriate mixing of raw materials, the granulating agent binder solution
(starch &gelatin paste) is added to form a uniform wet mass for granulation. The uniform
wet mass is then sent to the granulating department.
NOTE :- The binder solution must be added in small parts with constant blending to
avoid formation of lumps.
PRECAUTIONS:-
a) Coloring agents were added in hot gelatin sol. prior to starch sol. to avoid the
problem of MOTTLING.
b) To prevent the formation of lumps, starch solution should always be made in cold
water.
c) Constant stirring is required after addition of starch solution to avoid sticking of it
with vessel.
17
TABLE NO. 1 – LIST OF BINDERS
S.N.
Name % Used Solvents
1. Gum Acacia 2-5 Water, alcohol water
2. Traga Canth 1-3 Water (mucilage)
3. Gelatin 1-4 Water
4. Sucrose 2-20 Water
5. Starch 1-4 Water (paste)
6. Sodium Alginate 3-5 Water
7. Ammonium calcium alginate
3-5 Water
8. Methyl cellulose 1-4 Water
9. Sodium carboxymethyl cellulose
1-4 Water
10. Ethy Cellulose 0.5-2 Water
12. Poly vinylpyr rolidone 2-5 Water alcohol, alcohol water
13. Magnesium aluminium silicate
3-5 Water
GRANULATION:-
There are three methods generally used for granule formation -
(a) Wet Granulation Method
(b) Dry Granulation Method
(c) Direct Compression Method
Granulating mass received from the mixing unit is granulated by using multi mill
(specific granule size sieve is used).
Granules are then dried in the tray dryer. The tray dryer has the capacity of 200 kg
material (44 trays). For specific medicaments and particular granule size, specific time
periods and temperature are required for proper drying.
18
After production and drying of the granules, the granules are prepared for the
compression. For this various additives like glidants (starch, talc), disintegrating agent
(starch, cmc), lubricating agent (mag. Stearate) and antiadherent (talc, starch) are added in
specific conc. The prepared granules are then finally taken for the compression.
COMPRESSION
The granules received from the granulating section are compressed into the unit dosage
tablets by using single stoke multi punch tab. machine, has a good output.
TABLE NO.2 : - WATER SOLUBLE TABLET LUBRICANTS
S.N
.
Lubricant Suggested %
2. Sodium Chloride 5
3. Sodium Benzoate 5
4. Sodium Acetate 5
5. Sodium Oleate 5
6. Polyethylene Glycol 4000&6000 1-4
COATING SECTION
Application of coating to the tablet, which is an additional step in the manufacturing
process, increases the cost of product. The tablet is coated due to the following reasons-
i. To mask the taste, odor, or color of the tablet.
ii. To provide physical & chemical protection for the drug.
iii. To control the release of drug from the tablet.
iv. To protect drug from gastric environment.
Principle: - Tablet coating is the application of a coating composition to a moving bed of
tablets, with the concurrent use of a heated air to facilitate evaporation of the solvent. The
19
distribution of the coating is accomplished by either perpendicular or vertical movement
of the tablet.
Tablet Coating Pan
The coating pan is designed by the following basic components-
Coating Pan Circular metal pan mounted somewhat angularly on the
stand.
Blower & Exhaust.
Coating Sprayer.
Controlling devices
Working
1. Switch on the exhaust system and hot air blower.
2. Coating solution is filled in the coating sprayer and tablets to be coated filled in the
coating pan.
3. Carry out coating operation as per the procedure.
4. After completing the coating remove the coated tablets from the pan into a poly bag.
20
COLOURING AGENT
Tartazine Sunset yellow
Carmosine lake Iron oxide Red
Quinaline Yellow lake Erythrosine Lake
Iron Oxide Yellow Poneau- UR
Idacol Brillant blue FOF Supra
DISINTEGRANTS
Cross carmell sodium Starch 1800
Veegum granules
LUBRICANTS
Magnesium sterate Boricin
Stearic acid Talcum
Inwitor 900 glyceryl monosterate PEG
BINDERS
Acacia Gelatin
Primallose
DILUENTS
Floedac-100 (Lactose) Lactopress202
Dibasic calcium phosphate Vivapress (CaCO3)
FLAVOURING AGENT
Trusil peppermint special Orange flavor
Trusil pineapple special Chocolate flavor
PRESERVATIVES
Sodium benzoate Citric Acid
Sodium propyl paraben Sodium methyl paraben
Methyl Paraben
TABLE NO-3 LIST OF EXCIPIENTS
21
PACKAGING :-
The finished tablets received from compression section are packed into various types of
packaging. Packaging ensures the security and attractiveness of various tablet dosage
forms. Packaging of product is very important as it decides customer’s acceptability to a
great extent. Now-a-days, every company want to attract customers by any means to meet
competition and packaging is one of the best ways of attraction as it is also an art. In
JYOTI REMEDIES, packaging is done in different following ways:
Bulk packaging:
For bulk packaging of tablets, tablets are counted by a counting device. The hundred
tablets are counted once at a time. These counted tablets are packed into 100,500 and
1000 tablets poly pack and sealed with the plastic containers of specific size.
It is used rarely when drug supplied to a dispensing pharmacy. In this drug is packed in a
bulk quantity to reduce the cost and it is generally used for etc products.
Strip packaging:
A strip package is formed by feeding to webs of heat seal able flexible film through a
heated crimping roller. The product is dropped in to the pocket formed prior to forming
the final set of seal. A continuous strip of packets is formed. The strip of packets is cut to
the desired number of packets in the length. The strips formed are collected & usually
packed into folding cartons.
Blister packaging:
This type of packaging provides excellent environment protection, aesthetically pleasing
appeal and children resistance.
Blister packaging is formed by heat softening sheet of thermoplastic resin & vacuum
drawing the softened sheet of plastic in contoured mould. After cooling, the sheet is
released from the mould & proceeds for filling. The semi rigid blister previously formed
is filled with the product & lidded with heat seal able packing material. The lidding may
be push through or peel able type.
22
PROGRAMS ADOPTED FOR OBSERVING GMP AND TO BUILD QUALITY IN
THE PRODUCT:
TABLE:- 4 SOME COMMON PROBLEMS IN TABLETS
1. WEIGHT FLUCTUATIONS REASON
REMEDY
(a) Unsuitable granule size Change the granule size, usually small granules are for smaller tablets.
(b)
Granule Shape Prepare or round granules as possible to avoid uneven air spaces.
(c) Powder Content The proportion of fine powder should be kept below 20% of granulate.
(d)
Volume Differential The filling volume in the die should be as near as possible to the loose volume density.
(e) Flow control Lubricants-choice and quantity may be changed to control the flow of granules usually 1-5% are sufficient.
(f) Electrostatic Charging This can be eliminated by spraying the granules with water in order to increase their conductivity so that the electricity is conducted to the surrounding machine part are earthed
(g) Humidity If the granulate is too wet re dry the granules
(h)
Mechanical Factor
(i) Excessive compression speed
(ii) Vibration in hopper
(iii) Faculty guiding at lower
Reduce Speed
Use vibration absorbing mounting of the hopper
Replace warn filling and closing cams
2. DOUBLE FEED Double Feed may occur when tablets adhere to the punches or if they are not properly ejected due to in correct setting of ejectors check the setting of enjectors.
3. CAPPING
(a) Insufficient Moisture Spray the granules with water or water glycerin mixture.
(b)
Excessive Moisture Redry the granules.
23
(c) Insufficient or unsuitable binder In crease the binder or regranulate with a more suitable binder.
(d)
Excess air ingranulate Adjust the relative punch travels to compress in upper part of the die or use tapered dies.
(e) Excess powder content Sift out the fine powder or regranulate with different binders.
(f) Mechanical Factors
(i) Excessive pressure
(ii) Insufficient air escape
(iii) Tablet design & engraving
Reduce the compression speed.
Use tapered dies. Compression should take place in upper part of die. Apply precompresion before actual compression.
Change ratio between diameter diameter and thickness. Engraving grooves should be rounded. The ideal standard toper is 2/3 of compansion measurements.
4. CRACKING
(a) Excess moisture in granulate Redry the granules.
(b)
Unsuitable Lubricants Change the lubricants.
(c) Mechanical Factors
(i) Cam tolerance exceeded
(ii) Incorrect fitting of punches
Repair or replace the cam.
Recheck.
5. STICKING
(a) Excessive humidity Dry the granules and/or air condition the room.
(b)
Low melting point of Seperately granulate such ingradients.
(c) Insufficient cohesion individual ingredient
Slowly raise the compression pressure.
(d)
Excess powder Sift out excess powders
(e) Insufficient lubrication Increase or change the lubricant.
(f) Dies and punches dull Polish the dies and punches.
(g) Defective engraving design Use rounded edges.
24
There are different tests that are used for INPROCESS QUALITY CONTROL of
tablet dosage form. These are as follows:
Weight Variation Test
METHOD: Weigh 20 tablets selected at random and calculate the average weight not
more than two of the individual weights deviate from the average weight by more than
the percentage shown in table below and none deviates by more than twice that
percentage.
TABLE:- 5 WEIGHT VARIATION STANDARD
Average weight of tablet Percent deviation
80 mg or less 10
More than 80 mg but less than 250 mg 7.5
250 mg or more 5
HARDNESS TEST
Hardness of tablet determines its tensile strength. It must be such that the tablet can
withstand the shock of handling, packaging and shipping. It is measured in terms of
load/pressure. It is evaluated by the hardness tester by keeping the tablet in a vertical
position and crushing it. Different types of hardness testers can be used like-
Monsanto hardness tester
Pfizer hardness tester
Strong-Cobb tester
Erweka tester
Schleuniger tester
Hardness of 4 kg./cm.sq. is considered to be a minimum requirement.
25
FIG.-1 HARDNESS TESTER MONSANTO TYPE
FRIABILITY TEST
This test is performed to evaluate the ability of a tablet to withstand abrasion,
friction and shock in packing, handling and transportation. The apparatus used to
determine friability is called FRIABILITY TEST APPARATUS (ROCHE
FRIABILATOR). Friability value should not be more than 0.8%.
Formula-
(Wt. of tablet before test- wt. of tablets after test) 100
Wt. of tablet before test
FIG.-2 TABLET FRIABILITY TEST APPARATUS
26
DISINTIGRATION TEST
Disintegration is defined as that state in which no residue of the tablet or capsule remains
on the screen of the apparatus or, if a residue remains. It consists of fragments of
insoluble coating of the tablets or of capsule shells or is a soft mass with no palpable core.
It is an important step which determines the disintegration time of tablet.
TABLE:- 6 DISINTEGRATION STANDARD IP 1996
DISSOLUTION
The rate of dissolution plays an important role in the mechanism of drug absorption. The
drug is not absorbed unless it comes in the form of a solution. This is an important test for
drugs having poor solubility. Generally, drugs that have solubility greater than 1 % do not
27
TABLETS LIQUID at 37 ± 2`C
DISINTEGRATION
TIME
Uncoated Tablets Water 15 min.
Coated (Sugar/ Film) Water 60 min.
If any of tablet don’t disintegrate, replace water
with 0.1N HCl all 6 tablets must disintegrate
Enteric Coated 0.1N HCl
Should show no
disintegration for 2hrs.
Mixed Phosphate Buffer at pH=6.8 60 min.
Vaginal Tablets Water 30 min
Soluble & Dispersible
Tablets Water at 19-21`C 3 min
pose any problem but the drugs with lower solubility are primarily studied for dissolution
rate.
EQUIPMENTS USED IN TABLET SECTION
MIXING, GRANULATION & DRYING SECTION:
According to ‘Schedule M’ requirements.
TRAY DRYER:-
Mfg. By – Fabricated by industry itself.
Capacity – 200 kg. (44 trays)
Application - For drying
MULTIMILL:-
Mfg. By – Sehgal Industrial works, Delhi
Model : GMP S/S 304 Contact Parts
Principle - Impact & attrition, which reduces the clumps to
small & uniform size by milling & these are then
sieved or screened through sieve no. 8 or 10.
RPM : 750 to 3000 rpm.
Application - For granulation.
FIG. 3 MULTI MILL
28
SOP :-
1. from last batch.
2. Start the machine either in forward or reverse depending on size reduction to
be carried out .
3. Charge production into the hopper.
4. Open slide value slowly let the product enter the chamber.
5. Regulate the input by adjustment of slide value.
6. Maximum uniform output can be obtained by maintaining a constant rate of
feeding.
Caution !!!
OVEN FEEDING MAY JAM THE ROTOR AND BEATERS AND CAN DAMAGE
MASS MIXER:-
Mfg. By – Sehgal Industrial works, Delhi
Capacity – 150 kg.
Application - Holds the material & brings mixing by means of
moving screws, paddles or blades.
FIG 4 - MASS MIXER
29
SOP :-
1. Load the material from the container into the bowl as per the sequence
specified in the individual product batch manufacturing record.
2. Close the lid. Lock the three locking clamps.
3. Put the main switch on.
4. Before the starting the operation of the mixer ensure that it is cleaned as per
work instruction.
5. Load the materials and close the lid.
6. Start the dry mixing and run the mixer for 15 minutes.
7. At the binder paste / binder solution by opening the observation lid.
8. Selection of the time depends on what is specified in the individual BMR.
9. Add additional water it required and do the further mixing.
DOUBLE CONE BLENDER :-
FIG. 5 DOUBLE CONE BLENDER
a) Two cones are joined to a small cylindrical section.
b) This overcomes slow horizontal movement of solids found in a cylindrical
mixer.
30
c) Due to conical shape good rolling action of the solids prevail.
COATING PAN
This pan is used for film and sugar coating of tablets.
Salient features:-
1. Coating pan is made of SS 304
2. Totally enclosed with M.S. cladding with standard gearbox, motor and hot air
blowing arrangement.
3. Designed with M.S. fabricated structure.
4. Mounted on dynamounts, this avoids foundation.
FIG.:-6 COATING PAN
5. Coating Machine has variable speed drive and hot air blowing system in built in the
machine.
II. COMPRESSION SECTION:
1) SINGLE STROKE DOUBLE PUNCH MACHINE:-
Mfg. By – Ahiman Engineers.
Capacity – Each machine is capable of compressing one
lakh tablets per shift of 8 hrs. or 12000 tabs. per hr
per machine.
31
Application – For Compression.
FIG. 7 SINGLE STROKE DOUBLE PUNCH MACHINE
III. PACKAGING SECTION:
BLISTER PACKING MACHINE:-
Mfg. By – Global packaging, Ahmedabad.
Capacity - Generally 50,000 tablets per hour.(Maximum
capacity 90,000 tab./hr.)
Application - For packaging
FIG. 8 BLISTER PACKING MACHINE
STRIP PACKING MACHINE:-
Mfg. By – Nimcho Engineers, Delhi.
Capacity - 15,000 tablets per hour
Application - For packaging
32
FIG. 9 STRIP PACKING MACHINE
It is commonly used for the packaging of tablet and capsule. A strip package is formed by
feeding two webs of a heat sealable flexible film through a heated crimping roller. The
product is dropped into the pocket formed before forming the final set of seals. A
continuous strip of packed is formed which is cut to the desired number of packets in
length.
The product sealed between the two sheets of film usually has a seal around each tablet.
The seal can be in a sample rectangular farm or can be made to the shape of the product.
The material used for strip package are poly propylene, polyvinyl chloride, cellophane,
polyester, polyethylene, and saran.
33
FLOW CHART FOR MANUFACTURING OF TABLET
Production Order
Dispensing of Raw Material
Weighing
Sifting
Mixing
Preparation of Starch Paste
Binding
Wet Granulation
Drying
Size Reduction
Sifting of Lubricants
Lubrication of Granules
Q.A. Testing
34
Compression
In Process Checking
Coating
Packing Order
Dispensing of Packing Material
Strip / Blister sealing
Strips ready Cartooning
Cartons transferred to Finished Goods Room
35
CHAPTER 4
CAPSULE
SECTION
36
CAPSULE SECTION
A capsule is solid unit dosage form in which the medicament is enclosed in water soluble
shell or envelope. These are made by filling the drugs as powder, granules and pellets
into a preformed cylindrical shell or body. The capsules are available both as hard capsule
and soft capsule.
Advantages of Capsules
A capsule is a very popular dosage form these days due to the following advantages:-
(1) The drugs having unpleasant odor and taste can be administered by enclosing them in
a tasteless shell.
(2) The capsules release the medicament as and when desired in gastro-intestinal tract.
(3) Capsules are made from gelatin and hence they are therapeutically inert.
(4) They can be filled quickly and conveniently therefore the physician can charge the
dose and combination of drugs to suit the individual patient. This is an advantage
over tablets.
Disadvantages of Capsules
(1) The hygroscopic drugs cannot be filled in capsules. They absorb water present in the
capsule shell and hence make it very brittle, which ultimately breaks into pieces.
(2) The concentrated preparations which need previous dilution are unsuitable for
capsules because it may lead to irritation in stomach if administered as such.
Gelatin:-
Gelatin is the major component of the capsule and has been the material from which they
have traditionally been made. The reason for this is that gelatin possesses five basic
properties:-
(1) It is non-toxic, widely used in foodstuffs, and acceptable for use worldwide.
(2) It is a good film-forming material, producing a strong flexible film. The wall
thickness of a hard gelatin capsule is about 100 μm.
(3) Solutions of high concentration, 40% w/v, are mobile at 50°C. Other biological
polymers, such as agar, are not.
TABLE: - 7 TYPES OF MATERIAL FOR FILLING INTO HARD GELATIN CAPSULES.
37
Types of material for filling into hard gelatin capsules.
Dry solids
Powders
Pellets
Granules
Tablets
Semisolids
Thermosoftening mixtures
Thixotropic mixtures
Pastes
Liquids
Non-aqueous liquids
TABLE:- 8 CAPSULE NUMBER & ITS APPROXIMATE CAPACITY
Capsule no. Approx. capacity in mg
000 950
00 650
0 450
1 300
2 250
3 200
4 150
5 100
This section is divided into sub section.
38
Mixing Section
Capsule Filling Section
Polishing Section
Mixing Section
Here the raw material is received from raw material room. The weighed amount of raw
material is issued according to the master card in request by the raw material store keeper.
After sifting and uniforming by the cone blender, the mixed material is then sent to the
capsule filling room.
Capsule Filling Section
The mixed material received from the mixing section is then dispensed as capsule by the
help of semi automatic capsule filing machine (Hand operated capsule filling machine).
Filling Capacity - 300 capsule at a time
Time (Single operation) - 1.5 – 2 minute
Output (in 8 hr.) – 60,000 to 70,000 capsules
Polishing Section and Dedusting Section
After the filling the capsule are sent to the polishing unit. Here capsules are inspected
and polished with the help of liquid paraffin.
PACKAGING SECTION
The finished capsules received from the filling section are packed into various packing
forms.
Strip packing
Blister packing
Bulk packing
PRATICAL TIPS
39
When humidity is very low, the capsule become brittle
If stored at high humidity, the capsule become flaccid and losses their shape.
Requirement for relative humidity is 50 +5% in capsule section.
The requirement for temp. 22 +1oC in capsule section.
Size very from 000 to 5. 000 is largest size and 5 is smallest size.
Stored in high temperature are can also affect the qualities of hard gelatin capsule.
FLOW CHART FOR PRODUCTION OF CAPSULE
40
Production Order
Dispensing of Raw Material
Weighing
Sifting
Q.A. Testing
Filling
Polishing
In process checking
Packing Order
Dispensing of Packing Material
Strip / Blister Packaging
Sorting of Blister or Strip Pack
Strips Ready Cartooning
Cartoon Transferred to Finished Goods Room
41
IN PROCESS QUALITY CONTROL TEST ACCORDING TO
I.P.1996
Uniformity of container contents (For Capsules)
Select a sample of ten containers and count the no. of Capsules in each container. The
avg. no. of the contents in the ten containers is not less than the labeled amount and the
no. in any single container is not less than 98% and not more than 102% of labeled
amount.
If the requirement is not met, count the no. of the contents in each of ten additional
containers. The avg. no. in the 20 containers is not less than the labeled amount and the
no. in not more than 1 of the 20 containers is less than 98% or more than 102% of labeled
amount.
Uniformity of Weight
This test is not applicable to capsules that are required to comply with the test for
uniformity of content for all active ingredients.
TABLE:- 9 WEIGHT VARIATION SPECIFICATIONS AS PER I.P. 1996
Average wt. of capsule contents Percentage deviation
Less than 300 mg 10
300 mg or more 7.5
Uniformity of Contents
Note - This test is applicable to capsule than contain less than 10 mg or less than 10%
w/w of active ingredients. This test is not applicable for capsule containing multivitamins
and trace elements.
Requirement – 10 capsule selected through random sampling.
42
Disintegration Test
TABLE- 10 DISINTEGRATION TEST SPECIFICATIONS
CAPSULE LIQUID at 37 ± 2`C DISINTEGRATION TIME
Hard Gelatin Water 30 min.
Soft gelatin Water 60 min.
Enteric Coated 0.1N HCl
Should show no disintegration for
2hrs.
Mixed Phosphate Buffer at pH=6.8 60 min.
LIST OF EQUIPMENTS IN CAPSULE SECTION:
Capsule Dedusting Machine
Hand Operated Capsule Filling Machine
Double Cone Blender
Capsule Filling Unit
Weighing Balance
Disintegration Apparatus
CAPSULE DEDUSTING MACHINE
43
FIG. 10 CAPSULE DEDUSTING MACHINE
In this procedure, capsules are fed under rotating soft brushes, which serve to remove the
dust from the capsule shell. This operation must be accompanied by a vacuuming for
dust removal. Some materials are extremely difficult to remove by brushing, even to the
point of impregnating the brushes and causing scratches or deformation of the capsules.
HAND OPERATED CAPSULE FILLING MACHINE
OPERATION PROCEDURE (HAND OPERATED CAPSULE FILLING
MACHINE)
Loaded the empty capsule in loading tray.
Ensured that the inner side knob was pulled out with the help of cam liver the bodies
of capsules got tight and even grip.
Pushed the inner side knob in
By depressing lifting plate level, separate the capsule from bodies.
44
FIG.-11 HAND OPERATED CAPSULE FILLING MACHINE
i) Released the liver.
ii) Poured the pre weighed powder required for 300 capsules into powder tray.
iii) Rotated pin plate handle clock wise to compress powder in capsule bodies.
iv) Capsules were filled fully with the powder.
v) Remove powder tray replaced with loading tray with caps.
vi) By locking liver proper locking of capsule were done.
vii) Polishing and finishing was done.
Capsules were packed by strip blister packaging machine.
Label Printing Machine
M.R.P , manufacturing date, expiry date and batch no. are printed on the label by using
hand operated label printing machine.
RECORDS:-
The production in charge maintain following records in capsules section –
Flow sheet for entry of ingredients.
45
In process control sheets
Raw material issuer sheet
Packing material sheet
Sheet for finished goods store in ware house.
46
CHAPTER 5
LABELLING
LABELLING
47
The term ‘labelling’ means all labels and other written, printed, or graphic matter upon
any article or any of its containers or wrappers, or accompanying such articles.
The containers of all the drugs including patent or proprietary medicine are to be labeled
in accordance with the D&C rules 1945. Following particulars should be either printed or
written in indelible ink and should appear in a conspicuous manner on any drug and en
every other covering in which the container is packed.
Proper name of the drug.
Net contents in terms of wt., measure, volume, no. of units of
activity (In metric system.)
Content of active ingredients.
The name and address of the manufacturer.
Manufacturing license number or Mfg. Lic. No. or M.L.
Batch number – ‘ Batch no.’ or ‘B. No.’ or ‘Batch’ or ‘Lot no.’ or ‘
Lot’.
Expiry particulars, if any.
Precautionary information.
Storage conditions and manner of use.
General information such as ‘Physician’ sample, not for sale’ etc.
If the pack is not already printed, labeling normally follows
closuring.
48
CHAPTER 6
QUALITY CONTROL
&QUALITY
ASSURANCE
QUALITY CONTROL
49
The professional, social and legal responsibilities that rest with the pharmaceutical
Manufacturing for the assurance of product quality is tremendous. It is only through
well-organized, adequately staffed and accurately performed process and dosage form
control before, during and after production that adequate quality assurance of the product
can be achieved. It should be realized that no amount of dosage form testing and control
can maintain and assure products quality unless good manufacturing practices are
implemented systematically and process control is practiced vigorously. Products quality
must be built into, and not merely in the products.
The manufacturer can maintain the quality of his products by executing the
following functions: -
To control the sources of product quality, variation mainly in methods, machines
and men.
To ensure the correct and most appropriate, manufacturing and packaging
practices.
To assure that the testing results are in compliance with the standards or
specifications.
To assure the products stability and to perform other activities related to product
quality through a well-organized total quality assurance system.
In order that the quality control tests of the sample be indicative of the whole, proper
sample selection is essential. Usually two samples are chosen randomly from each batch
of capsules, tablets and liquids. The first samples is meant for immediate quality control
testing, whereas the second is intended to be maintained under appropriate storage
conditions to determine whether or not the samples
50
QUALITY CONTROL LABORATORY
Q.C. refers to the process of striving to produce a perfect product by a series of measures
requiring an organizes effect by the entire company or eliminate errors at every stage in
production .
Q.C. is the part of GMP concerned with sampling, specification and testing with the
organization, documentation and release procedure.
Various quality control parameter of the “Liquid and Solid” dosage form was evaluated.
The instruments that was in quality control laboratory are:-
51
QUALITY ASSURANCE
The assurance of product quality depends on more than just proper sampling and
adequate testing of various components and the finished dosage form prime responsibility
of maintaining product quality during production rest with the manufacturing department.
Removal of responsibility from manufacturing for producing a quality product can result
in imperfect composition, such as ingredient missing, sub potent or super potent addition
of ingredients or mix up of ingredients, mistakes in packaging or filling, such as product
contamination, mislabeling or deficient package and lack of conformance to product
registration. Quality assurance personnel establish control or check points to monitor the
quality of the product as it is processed and upon completion of manufacturing. These
begin with raw material and component testing and include in process, packaging,
labeling and finished product testing as well as back auditing and stability monitoring.
52
CHAPTER 7
STORE ROOM
53
STORE ROOM
RAW MATERIAL STORE ROOM:
The store room is the place where various materials are stored and preserved until they
are issued to the other departments. The area of a storeroom depends upon the nature and
capacity of the organization, nature of the item to be stored, frequency of purchasing and
issuing of the items. The quantity to be stored, nature of finished products etc. This unit
has a centralized store room consisting of a better control, better layout, less space, staff,
economy and better stock checking is rendered.
The storeroom is almost in the center of the unit and near the section so that
transportation of raw materials from store to various sections become very easy &
economic. In generally it consists of bulk drugs, raw materials coloring agents, flavoring
agents, sweetening agents, various suspending agents tools and spare parts of machine
etc. The materials such as coloring and flavoring agents, patent drugs, tools are stored in
specific metal, plastic, rubber and cardboard boxes in shelves and racks. The store is
categorized in zones for proper handling of the material.
The materials are issued to the production departments and the other departments as and
when desired by them. This section also maintains an up to date record of receipts and
issue of materials. The materials issued from the store are recorded. For maintaining an
up to date records, a store ledger is used. It provides information regarding the A/c
number of item, description of item, maximum, minimum and recorder and recorder
level, quantity received with date, quantities issued with date, batch no. regarding the
materials used all other necessary information.
PACKAGING MATERIAL STORE ROOM
An independent packing materials preparation and storage arrangements systems
was available at Jyoti remedies. Interestingly, the various packing materials, among
which the card board cartons of differing sizes were prepared at the first floor of the plant.
The packing materials included bottles, plastic boxes
54
CHAPTER 8
DOCUMENTATION
SECTION
55
DOCUMENTATION SECTION
DOCUMENTATION AND RECORDS:
Documentation is an essential part of the Quality Assurance system and, as such, shall be
related to all aspects of Good manufacturing practices (GMP). Its aim is to define the
specifications for all materials, method of manufacture and control, to ensure that all
personnel concerned with manufacture know the information necessary to decide whether
or not tot release a batch of a drug for sale and to provide an audit trail that shall permit
investigation of the history of any suspected defective batch.
DOCUMENTS REQUIRED
i) Labels
ii) Specifications & testing procedures
iii) Specifications for starting & packing materials
iv) Specifications for intermediate & bulk products
v) Specifications for finished products
vi) Master formulae
vii) Packing instructions
viii) Batch processing records
ix) Batch packaging records
x) Standard operating procedures ( SOPs) & records
xi) Miscellaneous
All these documents are maintained in the factory according to the legal requirements.
1. Master Formula Record:
To assure uniformity from batch to batch master formula (master production and control)
records for each drug product.
Procedure:
It is to be described in a written procedure and such written procedure shall be dated and
signed by competent technical staff and independently checked, checked dated and signed
by second person. Master formula record shall includes
56
i) Name and Strength of the product along with dosage form (if it is pharmacopoeial
product under trade name, both names will be given)
ii) The name and wt. measure of active ingredients per dosage unit or per unit
weight/measure of the product and tablet weight/measure of any dosage unit.
iii) A complete list of all the ingredients to be used in the manufacture of the product
indicating any special quality characteristics.
iv) An accurate statement of weight/measure of each ingredient (same weight system
should be used) required as per formula of dosage form and the weight/measure
actually to be used (e.g. overages to compensate losses during storage).
v) A statement of theoretical weight/measure at appropriate phase of processing.
vi) A statement of theoretical yield including permissible limits beyond which
investigation is required.
vii) A description of containers, closures and packaging materials to be used.
viii) A description of all vessels, equipments to be used in their preparation.
ix) Processing and packaging procedures.
x) In process controls to be exercised during processing and packaging.
xi) Precautions to be taken during manufacture and storage of semi-finished product.
2. Batch Manufacturing Records:-
Batch manufacturing records as per Schedule U are prepared for each batch of the drug
product. These should be based on master formula records. Method of preparation of
batch processing records should be such that transcription errors do not occur.
During the manufacturing information listed below should be recorded, signed and dated
by the persons responsible for processing operations:-
name of the product
batch number
date of commencement & completion of significant intermediate stages
name of the person responsible for each stage of production
57
initial of operators who carried out significant processes and initial of persons who
checked, wherever applicable.
Quantity, batch number, quality control report number of each ingredient actually
weighed and amount of any recovered material added.
In –process controls carried out their results and signature of person who performed.
Theoretical yield and actual yield at appropriate stage of production together with
explanation. If variation beyond expectation observed.
Authorization of any deviation if made.
HYGIENE & SANITATION
The factory was cleaned every morning with disinfectant and water.
Double door system was used in liquid section & capsule section to reduce the level of
recontamination.
Air curtain installed at the entrance of factory to reduce the dust content on cloths of
labor.
These were separate change room for men and women.
The kitchen of the factory was situated on first floor so as to reduce contamination.
Exhaust air, air conditioner, humidity meter were installed of various place in the factory.
Fire extinguisher was hanged on the wall of gallery.
58
CHAPTER 9
MARKETED
PRODUCTS
TABLE:- 11 LIST OF MARKETED PRODUCT
Brand Name Contents Pkg
Zeeclox LB capAmoxycillin 250mg,Cloxacillin 250mg, Lactic Acid
Bacillus 1.7 Billion capsuleCaps of 10s
59
Zeemox 250 cap Amoxycillin 250mg capsule Caps of 10s
Zeemox 500 cap Amoxycillin 500mg capsule Caps of 10s
Panlee DSRPantaprazole 40mg,Domperidone 30mg
sustained release capsuleCaps of 10s
Rabdom-DRabeprazole 20 mg & Domperidone
10 mg Cap10x10C
Rabdom-DSRRabeprazole 20 mg & Domperidone
30 mg Cap10x10C
DobeflowCalcium Dobesilate Monohydrate
BP 500 mg10x10C
Maxslim 60 Orlistat 60mg Capsules 10x10C
Maxslim 120 Orlistat 120mg Capsul;es 10x10C
Ferest-100 Cap Natural Micronised Progesterone 10x10C
Ferest-200 Cap Natural Micronised Progesterone 10x10C
Ecorich softulesVitamin E Acetate IP 400mcg & Code
liver oil BP 300mg
Softules of
10s
LipocinMethylcobalamin,Folic Acid,Vitamins B6 & Alpha
Lipoic Acid10x1x10C
Lycomax-PlusLycopene,LArginine,Betacarotene,Lutein,Vitamins
& Minerals10x1x10C
Pregmax-M Pregablin 75mg with Methylcobalamin 750 mcg 10x1x10C
Gabamax-M cap Gabapentin 300mg & Methylcobalamin 500mcg 10x1x10C
Maxtil 100 Cefpodoxime Proxetil USP 100mg DT Tablet 10x10T
Maxtil 200 Cefpodoxime Proxetil USP 200 mg tablet 10x10T
Roxime 250 tab Cefuroxime Axetil 250 mg tablet 10x10T
Roxime 500 tab Cefuroxime Axetil 500 mg tablet 10x10 T
Ceftis-200 Cefixime 200 mg Tablets 10x10T
Maxflox -200 Ofloxacin 200 mg tablet (Alu-Alu) 10x10T
Maxflox-400 Ofloxacin 400 mg tablet (Alu-Alu) 10x10T
Maxflox-O Ofloxacin 200 mg & Ornidazole 500 mg Tab 10x10T
Levomax 500 Levofloxacin 500 mg Tablets (Alu-Alu) 10x10T
Rabrol Rabeprazole 20 mg (Alu-Alu) 10x10T
Citrocalcium Alfacalcidol & Calcium Citrate Tablets 10x10T
Lubrilax Tab Sodium Picosulphate BP 10mg tablet 10x10T
Swiftase Tab Serratiopeptidase 10mg tablets 10x10T
60
Swiftact SDiclofenac50 mg, Serratiopeptidase
10 mg tablets10x10T
Swiftact 3D
Diclofenac Pottassium 50 mg &
Serratiopeptidase 15 mg &
Paracetamol 325 mg Tablets
10x10T
Swiftok
Diclofenac Pottassium 50mg, PCM 500mg,
Chlorzoxazone 250mg, Magnesium Trisilicate 100
mg Tablets
10x10T
Petra Plus tab Tramadol 50mg,Paracetamol IP 500mg 10x10T
Nimbra Nimesulide Tablets 25x10T
Nimbra Plus Nimesulide & Paracetamol Tablets 25x10T
HB Rise TabFerrous Ascorbate eq.to elemental
iron 100mg,Folic Acid IP 1.5mg Tablet10x10T
NovacalAlfacalcidol 0.25mcg & Calcium Citrate 1200mg
Tablets10x10T
Balaneuron-Forte
Benfotiamine,Methylcobalamin
Adenosylcobalamin,Folic acid,Pyriodoxine
Hydrochloride
10x10T
Zeeclox Kid LB
tab
Amoxycillin 125mg,Cloxacillin 125mg,
Lactic Acid Bacillus 1.7 Billion tabletsTabs of 10s
Zeemox 250 DT Amoxycillin 250mg Dispersible tab Tabs of 10s
Zeemox CV 625Amoxycillin 500mg, Clavulanic Acid
125mg tabletTabs of 10s
Zithmax 500 tab Azithromycin 500mg tablet Tabs of 10s
Zeemol 650 Paracetamol 650mg Tabs of 10s
Mefmol PlusMefenamic Acid IP 500mg,Paracetamol
IP 450mgTabs of 10s
61
CHAPTER 10
WORK DONE
UNDER
PRACTICAL
TRAINING
WORK DONE UNDER PRACTICAL TRAINING
“Accept challenges, so you can feel the joy of victory” this is right for me, when I go to
this industry “JYOTI REMEDIES”. As it was challenge for me to join this, after joining I
62
feel that I have gained much more knowledge about the pharmacy & works handled in
industry. There was a complete friendly nature of the men power of industry.
The factory was cleaned every morning with disinfectant & water, so that hygienic
environment can be made. I am very grateful to Mr. C.P. Kuriakose (M.D.) & Mr. Sudhir
Sharma (M.D.) who give me complete guidance which was necessary for me in
completion of this training. JYOTI REMEDIES has bright future as it is among the fastest
growing pharmaceutical companies.
TABLET :-
Brand Name – Mefmol Plus
ANTI-INFLAMATORY, ANALGESIC
Each uncoated tablet contains:
Mefenamic Acid I.P. 500 mg
Paracetamol I.P. 450 mg
Formula for 58,000 tablets:
For 1 tablet, Mefenamic Acid I.P. = 500 mg
For 58,000 tablets, Mefenamic Acid I.P. = 500*58,000= 29.0 Kg
For 1 tablet Paracetamol I.P. = 450 mg
For 58,000 tablets, Paracetamol I.P. = 450*58,000=26.10 Kg
Total active ingredients = 55.10 Kg
Wt. Of 1 tab. = 1.20 gm
Total Wt. = 1.20*58,000=69.6 Kg
Lubricants:
1) Talc - 2.73%
63
For 58,000 Tablets,
(2.73*69.6)/100 = 1.9 Kg.
2) Magnesium stearate - 1.27%
For 58,000 Tablets,
(1.27*69.6)/100 = .88 Kg.
3) Aerosil - 0.907%
For 58,000 Tablets,
(0. 907*69.6/100 = 500 gm
Total lubricants used = 0.63 Kg
Disintegrants:
Starch - 4.53%
For 58,000 Tablets,
(4.53*69.6)/100 = 3.15 Kg.
Binders:
1) Starch - 4. %
For 58,000 Tablets,
(4*69.6)/100 = 2.78 Kg.
2) Gelatin – 1%
For 58,000 Tablets,
(1*69.6)/100 = 0.7 Kg.
Moisture content:
Moisture - 2 %
64
For 58,000 Tablets,
(2*69.6)/100 = 1.39 Kg.
Preservative:
Sodium benzoate - 0.0324 %
For 58,000 Tablets,
(0.0324*69.6)/100 = 0.02 gm.
Diluents:
1) Talc - 2.125 Kg.
2) Starch - 2.125 Kg.
65
CHAPTER 10
CONCLUSION
CONCLUSION
66
As we all know the main purpose of industrial training is to improve the practical skill of
the trainee and to acquire him with the environment of the industry and to develop
professionalism.
Working in Jyoti remedies as a trainee was an excellent experience. I had learnt many
new techniques regarding formulation of Tablet & capsule dosage forms. The location
and layout of factory was according to the GMP requirements. The technical staff of the
factory was very talented, expert in their work. All the employees and workers were very
cooperative, disciplined and professional.
The Q.C. section was well equipped and all the standards and Q.C. Tests were performed
according to the official pharmacopoeias very strictly.
In my opinion Jyoti remedies has wide scope for more development in upcoming years
and future of the company is bright because of good management and skilled staff in
production department.
67
BIBLIOGRAPHY
BIBLIOGRAPHY
68
1. Indian Pharmacopoeia, Government of India, Ministry of Health and Family
Welfare, The controller of Publication, 1996, New Delhi.
2. Lachman, L. and Libberman, A. (1991) The Theory and Practice of Industrial
Pharmacy, Varghese Publishing House, Bombay.
3. Remington’s – The science and practice of pharmacy, international student
edition, 20th ed., 2000 Philadelphia College of Pharmacy and Science,
Philadelphia.
4. Ansel’s Pharmaceutical Dosage forms and Drug Delivery Systems’ 8 th ed.,
B.I. Publications Pvt. Ltd., Lippincott Williams and Wilkins, Philadelphia.
5. Bentley’s Text book of Pharmaceutics, 8th ed., Published by All India
Traveller Book Seller, Delhi.
6. Aulton, M. Pharmaceutics – The science of Dosage from Design International
Student edition, London.
7. Kohli, D.P.S. and Shah, D.H., Drug formulations, Manual Eastern Publishers,
New Delhi.
8. Mithal B.N., ‘Text Book of Pharmaceutical Formulation, Vallabh Prakashan,
Delhi.
9. United State Pharmacopoeia, 23rd edition.
10. P.P. Sharma – How to practice GMP (Good Manufacturing Practices) 4 th Ed.,
Vandana Publication Pvt. Ltd., Delhi P.No. 55-57, 215-296
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