CHAPTER 1<br />AN INTRODUCTION AND LAYOUT<br />INTRODUCTION<br />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.<br />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<br />Consistency in maintaining high quality drugs<br />Constantly expanding products portfolio<br />One time product delivery<br />State of the art manufacturing facilities<br />Conforming to prevalent and demanding international standards<br />Today Jyoti Remedies commands a reputation of upcoming pharmaceutical thespian in the pharma world with 4 Divisions.The group of concerns are:<br />Ce-Biotec (P) Ltd.<br />Ce-Chem Formulations<br />Jupiter Drugs<br />CHAPTER 2<br />ORGANISATION<br />MANAGING BODY<br />Board of Directors:<br />Managing Director (M.D.):Mr. C.P. Kuriakose & Mr. Sudhir Sharma<br />Others:<br />Production Incharge:Mr. Lal Singh<br />Q.C. Incharge:Mr. Bhaskar Patel<br />Store Incharge:Mr. Manoj Sharma<br />Maintenance Incharge:Mr. Azad Ali <br />Marketing Incharge:Mr. Ajay Sharma<br />Computer Operator :Miss Kalpna<br />Corporate Office :Ce-Biotec (P) Ltd.<br />Ce Pe Towers, tana, P.B. No.23<br /> Irinjalakuda, Trissus 680101<br /> Kerala, India Tel. No. 0480-2825605 <br />Factory at:Jyoti Remedies (P) Ltd.<br />Vill. Kailer, Subhathu road<br />P.O. saproon, Solan India 173211<br />Tel. No. 0192-228378, 09805559011<br />GMP FOR PREMISES AND MATERIALSTABLE 2 SPECIFIC REQUIREMENTS OF PLANT & EQUIPMENT:<br />S.noSectionArea (minimum)For basic installationFor ancillary areaTablets60 Sq. m (Uncoated)30 Sq. m (Coated)20 Sq. m10 Sq. mCapsules25 Sq. m10 Sq. mRepacking of drugs & pharmaceuticals35 Sq. m<br />1 General requirements:-<br />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.<br />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.<br />2 Ware housing area: <br />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.<br />3 Production area:<br />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. <br />4 Ancillary area:<br />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.<br />5 Personnel:<br />The manufacturing is conducted under the direct supervision of Mr Lal Singh. (Manufacturing Incharge). The company has very well qualified and competent technical staff.<br />6Health, clothing and sanitation of workers:<br />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.<br />7Precaution against mix-up and cross contamination:<br />Recalled or rejected material and other material that are not to be processed or recovered are kept in segregated, enclosed areas.<br />8Sanitation in manufacturing premises:<br />Manufacturing premises of Jyoti Remedies is cleaned and maintained in an orderly manner. It is free from accumulated waste, dust, debris and other material. <br />9Raw materials:<br />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. <br />10Equipment:<br />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.<br />11Labels and other printed materials:<br />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.<br />Example:<br />Under testYellowPassedGreenRejectedRed<br />12Master formula record: <br />Jyoti Remedies has master formula records relating to all manufacturing procedure for each product and batch size to be manufactured.<br />13Batch processing records:<br />These records are based on the relevant parts of the currently approved master formula.<br /> JYOTI REMEDIES <br /> Vill.-Kailer, Subhathu road P.O. saproon, Solan<br /> 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……………………INGREDIENTSLabel ClaimC.R. No.Qty. Req.Qty. UsedStock LedgerKg.gm.Kg.gm.Active IngredientsFILLERSStarch I.P.Di Cal. Phos. I.P.Lactose I.P.Date of Mixing ……………… Duration……….Hrs. Total Wt =………………..PASTE (Binders)StarchGelatinSod. BenzoateColourDate Of Granulation……………………….. Dried at =………………………………Time Required…………………………… Wt. Of Dried Granules……………………LUBRICANTSStarch (Dried)TalcumMag. Stearate<br />TOTAL Wt.=<br />Weight of Lubricated Granules =_______________________Kg<br />Added Lubricated Granules of previous<br />Batch No. =_______________________Kg<br /> (wt. Per tablet______________mg)<br /> <br />Total wt. Of Lubricated Granules ready for<br />Compression = Kg<br /> <br />COMPRESSION:<br />Date of Compression_____________<br />Weight of One tab. Should be_______________mg<br />Punch size Diameter_____________ Width_______________ Length___________<br />Appearance____________________________ Surface________________________<br />Scored___________________________ Embossed__________________________<br />Hardness__________________Kg/cm2 Disintegration Time____________________<br />Friability_______________% Weight of 20 tablets______________gm<br />Average weight per tablet______________<br />Permissible limit of wt. Variation____________<br />Individual wt. Of 20 tablets in mgs.<br />PACKINGS<br />Packing Material Required:<br />PARTICULARSQTY. USEDDESTROYEDTOTALSTOCK LEDGERBoxes (Plastic)PouchLabelsStrips Qty.CartoonsCatch Cover<br />Printed Particulars On Label Batch No._________________<br />Rate Strip (per 10 tabs) =_________________<br />Mfg. Date__________________ Exp. Date____________________<br />Date______________<br />No. of BoxQty. per BoxTotal Tablets<br />Samples:For Analysis:<br />For Quality Control Deptt.:<br />________________________<br />Total=<br />________________________<br />Percentage Yield<br />Date of Completion____________________<br />Quality Control:<br />Sample Tested by______________________________________________________<br />Analytical Report No._____________________ Date__________________________<br />Result: Passes/Fails<br />Date of Release For Warehouse___________________________________________<br />_____________________________________________________________________<br />Quantity Released To Warehouse:<br />PACKINGNO. OF BOXESSTOCK LEDGER<br />Date Of Completion:___________________<br />Signature Assistant Mfg. ChemistSignature Analytical Chemist<br />Signature Mfg. Chemist In-charge_______________________<br />In-Process Quality Control :<br />Hardness of tablet________________Kg/cm2 Friability____________________<br />Disintegration Time_______________ Wt. Of 20 Tablets _______________gm.<br />Average Wt. Per Tablet_________________ Claim_______________________<br />Permissible Limit Of Wt._______________<br />Individual Wt. Of 20 Tablets in mgs.<br />Wt. Of 20 Tablets at intervals of 30 Minutes in gm.<br /> <br /> Signature of Analytical Chemist<br />CHAPTER 3<br />TABLET SECTION<br />INTRODUCTION<br />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.<br />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. <br />Defination of Tablet According To I P – 1996<br />Tablets are solid dosage form each containing a unit dose of one or more medicaments. They are intended for oral administration.<br />Defination of Tablet According to USP – 23rd Edition:-<br />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:-<br />There are different processes, which are involved in the manufacturing of tablet. These are as follows:-<br />Weighing section<br />Granulation section<br />Drying section<br />Compression section<br />In Process Quality control<br />Coating section<br />Packaging section<br />MIXING<br />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. <br />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.<br />Preparation of Binder solution (Starch and Gelatin Paste):-<br />a) The hot gelatin solution of specified quantity was prepared using D.M. water.<br />b) Suitable coloring agents were dissolved in small quantity of water and then incorporated in hot gelatin solution with stirring until it mixes uniformly.<br />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.<br />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.<br />NOTE :- The binder solution must be added in small parts with constant blending to avoid formation of lumps.<br /> PRECAUTIONS:-<br />Coloring agents were added in hot gelatin sol. prior to starch sol. to avoid the problem of MOTTLING.<br />To prevent the formation of lumps, starch solution should always be made in cold water.<br />Constant stirring is required after addition of starch solution to avoid sticking of it with vessel.<br />TABLE NO. 1 – LIST OF BINDERS<br />S.N.Name% UsedSolvents1.Gum Acacia2-5Water, alcohol water2.Traga Canth1-3Water (mucilage)3.Gelatin1-4Water4.Sucrose2-20Water5.Starch1-4Water (paste)6.Sodium Alginate3-5Water7.Ammonium calcium alginate3-5Water8.Methyl cellulose1-4Water9.Sodium carboxymethyl cellulose1-4Water10.Ethy Cellulose0.5-2Water12.Poly vinylpyr rolidone2-5Water alcohol, alcohol water13.Magnesium aluminium silicate3-5Water<br /> <br />Granulation:-<br />There are three methods generally used for granule formation -<br />(a)Wet Granulation Method<br />(b)Dry Granulation Method<br />(c)Direct Compression Method<br />Granulating mass received from the mixing unit is granulated by using multi mill (specific granule size sieve is used). <br />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. <br />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.<br />COMPRESSION<br />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.<br />TABLE NO.2 : - WATER SOLUBLE TABLET LUBRICANTS<br />S.N.Lubricant Suggested %2.Sodium Chloride53.Sodium Benzoate54.Sodium Acetate55.Sodium Oleate56.Polyethylene Glycol 4000&60001-4<br />COATING SECTION <br />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-<br />i.To mask the taste, odor, or color of the tablet.<br />ii.To provide physical & chemical protection for the drug.<br />iii.To control the release of drug from the tablet.<br />iv.To protect drug from gastric environment.<br />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 distribution of the coating is accomplished by either perpendicular or vertical movement of the tablet.<br />Tablet Coating Pan<br />The coating pan is designed by the following basic components-<br /><ul><li>Coating Pan Circular metal pan mounted somewhat angularly on the stand.
Controlling devices</li></ul>Working<br />Switch on the exhaust system and hot air blower.<br />Coating solution is filled in the coating sprayer and tablets to be coated filled in the coating pan.<br />Carry out coating operation as per the procedure.<br />After completing the coating remove the coated tablets from the pan into a poly bag.<br />COLOURING AGENTTartazine Sunset yellowCarmosine lakeIron oxide RedQuinaline Yellow lakeErythrosine LakeIron Oxide YellowPoneau- URIdacol Brillant blue FOF SupraDISINTEGRANTSCross carmell sodium Starch 1800Veegum granules LUBRICANTSMagnesium sterate BoricinStearic acid TalcumInwitor 900 glyceryl monosterate PEGBINDERSAcacia GelatinPrimalloseDILUENTSFloedac-100 (Lactose) Lactopress202Dibasic calcium phosphate Vivapress (CaCO3)FLAVOURING AGENTTrusil peppermint special Orange flavorTrusil pineapple special Chocolate flavorPRESERVATIVESSodium benzoate Citric AcidSodium propyl paraben Sodium methyl parabenMethyl Paraben <br />Table No-3 List of Excipients<br />PACKAGING :-<br />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:<br />Bulk packaging:<br />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.<br />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.<br />Strip packaging: <br />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. <br />Blister packaging:<br />This type of packaging provides excellent environment protection, aesthetically pleasing appeal and children resistance.<br />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.<br />PROGRAMS ADOPTED FOR OBSERVING GMP AND TO BUILD QUALITY IN THE PRODUCT:<br />TABLE:- 4 SOME COMMON PROBLEMS IN TABLETS<br />1.WEIGHT FLUCTUATIONS REASONREMEDY(a)Unsuitable granule sizeChange the granule size, usually small granules are for smaller tablets.(b)Granule ShapePrepare or round granules as possible to avoid uneven air spaces.(c)Powder ContentThe proportion of fine powder should be kept below 20% of granulate.(d)Volume DifferentialThe filling volume in the die should be as near as possible to the loose volume density.(e)Flow controlLubricants-choice and quantity may be changed to control the flow of granules usually 1-5% are sufficient.(f)Electrostatic ChargingThis 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)HumidityIf the granulate is too wet re dry the granules(h)Mechanical Factor(i) Excessive compression speed(ii) Vibration in hopper(iii) Faculty guiding at lowerReduce SpeedUse vibration absorbing mounting of the hopperReplace warn filling and closing cams2.DOUBLE FEEDDouble 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 MoistureRedry the granules.(c)Insufficient or unsuitable binderIn crease the binder or regranulate with a more suitable binder.(d)Excess air ingranulateAdjust 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 & engravingReduce 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 granulateRedry the granules.(b)Unsuitable LubricantsChange the lubricants.(c)Mechanical Factors(i) Cam tolerance exceeded(ii) Incorrect fitting of punchesRepair or replace the cam.Recheck.5.STICKING(a)Excessive humidityDry the granules and/or air condition the room.(b)Low melting point ofSeperately granulate such ingradients.(c)Insufficient cohesion individual ingredientSlowly raise the compression pressure.(d)Excess powderSift out excess powders(e)Insufficient lubricationIncrease or change the lubricant.(f)Dies and punches dullPolish the dies and punches.(g)Defective engraving designUse rounded edges.<br />There are different tests that are used for INPROCESS QUALITY CONTROL of tablet dosage form. These are as follows:<br />Weight Variation Test<br />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.<br />TABLE:- 5 WEIGHT VARIATION STANDARD<br />Average weight of tabletPercent deviation80 mg or less10More than 80 mg but less than 250 mg7.5250 mg or more5<br />HARDNESS TEST<br />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-<br />Monsanto hardness tester<br />Pfizer hardness tester<br />Strong-Cobb tester<br />Erweka tester<br />Schleuniger tester<br />Hardness of 4 kg./cm.sq. is considered to be a minimum requirement.<br /> Fig.-1 Hardness Tester Monsanto Type<br />FRIABILITY TEST<br />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%.<br />Formula-<br />(Wt. of tablet before test- wt. of tablets after test) 100<br />Wt. of tablet before test<br />1838325327025<br />Fig.-2 Tablet Friability Test Apparatus<br />DISINTIGRATION TEST<br />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.<br />TABLE:- 6 DISINTEGRATION STANDARD IP 1996<br />TABLETSLIQUID at 37 ± 2`CDISINTEGRATION TIMEUncoated Tablets Water15 min.Coated (Sugar/ Film)Water60 min.If any of tablet don’t disintegrate, replace water with 0.1N HCl all 6 tablets must disintegrateEnteric Coated0.1N HClShould show no disintegration for 2hrs.Mixed Phosphate Buffer at pH=6.860 min.Vaginal TabletsWater30 minSoluble & Dispersible TabletsWater at 19-21`C3 min<br />DISSOLUTION<br />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 pose any problem but the drugs with lower solubility are primarily studied for dissolution rate.<br />EQUIPMENTS USED IN TABLET SECTION<br />MIXING, GRANULATION & DRYING SECTION: <br /> According to ‘Schedule M’ requirements.<br />TRAY DRYER:-<br />Mfg. By – Fabricated by industry itself.<br />Capacity – 200 kg. (44 trays)<br />Application-For drying<br />MULTIMILL:-<br />Mfg. By – Sehgal Industrial works, Delhi<br />Model:GMP S/S 304 Contact Parts<br />Principle-Impact & attrition, which reduces the clumps to <br /> small & uniform size by milling & these are then <br /> sieved or screened through sieve no. 8 or 10. <br />RPM:750 to 3000 rpm.<br />Application-For granulation.<br />FIG. 3 MULTI MILL<br />SOP :-<br />from last batch.<br />Start the machine either in forward or reverse depending on size reduction to be carried out .<br />Charge production into the hopper.<br />Open slide value slowly let the product enter the chamber.<br />Regulate the input by adjustment of slide value.<br />Maximum uniform output can be obtained by maintaining a constant rate of feeding. <br />Caution !!!<br />OVEN FEEDING MAY JAM THE ROTOR AND BEATERS AND CAN DAMAGE<br />MASS MIXER:-<br />Mfg. By – Sehgal Industrial works, Delhi<br />Capacity – 150 kg.<br />Application-Holds the material & brings mixing by means of <br /> moving screws, paddles or blades. <br />Fig 4 - MASS MIXER<br />SOP :-<br />Load the material from the container into the bowl as per the sequence specified in the individual product batch manufacturing record.<br />Close the lid. Lock the three locking clamps.<br />Put the main switch on.<br />Before the starting the operation of the mixer ensure that it is cleaned as per work instruction.<br />Load the materials and close the lid.<br />Start the dry mixing and run the mixer for 15 minutes.<br />At the binder paste / binder solution by opening the observation lid.<br />Selection of the time depends on what is specified in the individual BMR.<br />Add additional water it required and do the further mixing. <br />DOUBLE CONE BLENDER :-<br />Fig. 5 DOUBLE CONE BLENDER<br />Two cones are joined to a small cylindrical section. <br />This overcomes slow horizontal movement of solids found in a cylindrical mixer.<br />Due to conical shape good rolling action of the solids prevail.<br />COATING PAN<br />This pan is used for film and sugar coating of tablets.<br />Salient features:-<br />Coating pan is made of SS 304<br />Totally enclosed with M.S. cladding with standard gearbox, motor and hot air blowing arrangement.<br />Designed with M.S. fabricated structure.<br />Mounted on dynamounts, this avoids foundation.<br /> <br />Fig.:-6 Coating Pan<br />Coating Machine has variable speed drive and hot air blowing system in built in the machine.<br />II. COMPRESSION SECTION:<br />1) SINGLE STROKE DOUBLE PUNCH MACHINE:-<br />Mfg. By – Ahiman Engineers.<br />Capacity – Each machine is capable of compressing one <br />lakh tablets per shift of 8 hrs. or 12000 tabs. per hr per machine.<br />Application – For Compression.<br />Fig. 7 SINGLE STROKE DOUBLE PUNCH MACHINE<br />III. PACKAGING SECTION:<br />BLISTER PACKING MACHINE:-<br />Mfg. By – Global packaging, Ahmedabad.<br />Capacity-Generally 50,000 tablets per hour.(Maximum <br /> capacity 90,000 tab./hr.)<br />Application - For packaging<br /> <br />Fig. 8 BLISTER PACKING MACHINE<br />STRIP PACKING MACHINE:-<br />Mfg. By – Nimcho Engineers, Delhi.<br />Capacity-15,000 tablets per hour<br />Application - For packaging<br />Fig. 9 STRIP PACKING MACHINE<br />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.<br />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.<br />The material used for strip package are poly propylene, polyvinyl chloride, cellophane, polyester, polyethylene, and saran.<br />FLOW CHART FOR MANUFACTURING OF TABLET<br />Production Order<br /><br />Dispensing of Raw Material<br /><br />Weighing<br /><br />Sifting<br /><br />Mixing<br /><br />Preparation of Starch Paste <br /><br />Binding<br /><br />Wet Granulation<br /><br />Drying<br /><br />Size Reduction<br /><br />Sifting of Lubricants<br /><br />Lubrication of Granules<br /><br />Q.A. Testing<br /><br />Compression<br /><br />In Process Checking <br /><br />Coating<br /><br />Packing Order<br /><br />Dispensing of Packing Material<br /><br />Strip / Blister sealing<br /><br />Strips ready Cartooning<br /><br />Cartons transferred to Finished Goods Room<br />chapter 4<br />capsule <br />section<br />CAPSULE SECTION<br />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.<br />Advantages of Capsules<br />A capsule is a very popular dosage form these days due to the following advantages:-<br />The drugs having unpleasant odor and taste can be administered by enclosing them in a tasteless shell.<br />The capsules release the medicament as and when desired in gastro-intestinal tract.<br />Capsules are made from gelatin and hence they are therapeutically inert.<br />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.<br />Disadvantages of Capsules<br />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.<br />The concentrated preparations which need previous dilution are unsuitable for capsules because it may lead to irritation in stomach if administered as such.<br />Gelatin:-<br />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:-<br />It is non-toxic, widely used in foodstuffs, and acceptable for use worldwide.<br />It is a good film-forming material, producing a strong flexible film. The wall thickness of a hard gelatin capsule is about 100 μm.<br />Solutions of high concentration, 40% w/v, are mobile at 50°C. Other biological polymers, such as agar, are not.<br /> Table: - 7 Types of material for filling into hard gelatin capsules.<br />Types of material for filling into hard gelatin capsules.Dry solidsPowdersPelletsGranulesTabletsSemisolidsThermosoftening mixturesThixotropic mixturesPastesLiquidsNon-aqueous liquids<br /> Table:- 8 Capsule Number & Its Approximate Capacity <br />Capsule no.Approx. capacity in mg00095000650045013002250320041505100<br />This section is divided into sub section.<br />Mixing Section<br />Capsule Filling Section<br />Polishing Section<br />Mixing Section <br />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.<br />Capsule Filling Section <br />The mixed material received from the mixing section is then dispensed as capsule by the<br />help of semi automatic capsule filing machine (Hand operated capsule filling machine).<br /> Filling Capacity - 300 capsule at a time <br />Time (Single operation) - 1.5 – 2 minute<br />Output (in 8 hr.) – 60,000 to 70,000 capsules<br />Polishing Section and Dedusting Section <br />After the filling the capsule are sent to the polishing unit. Here capsules are inspected and polished with the help of liquid paraffin.<br />PACKAGING SECTION<br />The finished capsules received from the filling section are packed into various packing forms.<br />Strip packing<br />Blister packing<br /><ul><li>Bulk packing</li></ul>PRATICAL TIPS<br />When humidity is very low, the capsule become brittle<br />If stored at high humidity, the capsule become flaccid and losses their shape.<br />Requirement for relative humidity is 50 +5% in capsule section.<br />The requirement for temp. 22 +1oC in capsule section.<br />Size very from 000 to 5. 000 is largest size and 5 is smallest size.<br />Stored in high temperature are can also affect the qualities of hard gelatin capsule. <br />FLOW CHART FOR PRODUCTION OF CAPSULE<br />Production Order<br />Dispensing of Raw Material<br />Weighing<br />Sifting<br />Q.A. Testing<br />Filling<br />Polishing<br />In process checking<br />Packing Order<br />Dispensing of Packing Material<br />Strip / Blister Packaging<br />Sorting of Blister or Strip Pack<br />Strips Ready Cartooning<br />Cartoon Transferred to Finished Goods Room<br />IN PROCESS QUALITY CONTROL TEST ACCORDING TO I.P.1996<br />Uniformity of container contents (For Capsules) <br />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.<br />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. <br />Uniformity of Weight <br />This test is not applicable to capsules that are required to comply with the test for uniformity of content for all active ingredients.<br />Table:- 9 Weight Variation Specifications as per I.P. 1996<br />Average wt. of capsule contentsPercentage deviationLess than 300 mg10300 mg or more7.5<br />Uniformity of Contents<br />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. <br />Requirement – 10 capsule selected through random sampling.<br />Disintegration Test <br />Table- 10 Disintegration Test Specifications<br />CAPSULELIQUID at 37 ± 2`CDISINTEGRATION TIMEHard GelatinWater30 min.Soft gelatinWater60 min.Enteric Coated0.1N HClShould show no disintegration for 2hrs.Mixed Phosphate Buffer at pH=6.860 min.<br />LIST OF EQUIPMENTS IN CAPSULE SECTION:<br />Capsule Dedusting Machine<br />Hand Operated Capsule Filling Machine<br />Double Cone Blender<br />Capsule Filling Unit<br />Weighing Balance<br />Disintegration Apparatus<br /> <br />CAPSULE DEDUSTING MACHINE<br />1619250303530 <br />Fig. 10 Capsule Dedusting Machine<br />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.<br />HAND OPERATED CAPSULE FILLING MACHINE<br />OPERATION PROCEDURE (HAND OPERATED CAPSULE FILLING MACHINE)<br />Loaded the empty capsule in loading tray.<br />Ensured that the inner side knob was pulled out with the help of cam liver the bodies of capsules got tight and even grip.<br />Pushed the inner side knob in<br />By depressing lifting plate level, separate the capsule from bodies.<br />Fig.-11 Hand Operated Capsule Filling Machine<br />Released the liver.<br />Poured the pre weighed powder required for 300 capsules into powder tray.<br />Rotated pin plate handle clock wise to compress powder in capsule bodies.<br />Capsules were filled fully with the powder.<br />Remove powder tray replaced with loading tray with caps.<br />By locking liver proper locking of capsule were done.<br />Polishing and finishing was done.<br />Capsules were packed by strip blister packaging machine.<br />Label Printing Machine <br />M.R.P , manufacturing date, expiry date and batch no. are printed on the label by using hand operated label printing machine. <br />RECORDS:-<br />The production in charge maintain following records in capsules section –<br />Flow sheet for entry of ingredients.<br />In process control sheets<br />Raw material issuer sheet<br />Packing material sheet<br />Sheet for finished goods store in ware house.<br />CHAPTER 5<br /> <br />LABELLING<br />LABELLING<br />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.<br />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.<br /><ul><li>Proper name of the drug.
Net contents in terms of wt., measure, volume, no. of units of activity (In metric system.)
General information such as ‘Physician’ sample, not for sale’ etc.
If the pack is not already printed, labeling normally follows closuring.</li></ul>CHAPTER 6<br />QUALITY CONTROL<br /> &<br />QUALITY ASSURANCE<br />QUALITY CONTROL<br />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.<br /><ul><li>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.</li></ul>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 <br /> <br />QUALITY CONTROL LABORATORY<br />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 .<br />Q.C. is the part of GMP concerned with sampling, specification and testing with the organization, documentation and release procedure.<br />Various quality control parameter of the “Liquid and Solid” dosage form was evaluated. The instruments that was in quality control laboratory are:- <br />QUALITY ASSURANCE<br />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.<br />CHAPTER 7<br />STORE ROOM<br />STORE ROOM<br />RAW MATERIAL STORE ROOM:<br />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.<br />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.<br />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.<br />PACKAGING MATERIAL STORE ROOM <br />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<br />CHAPTER 8<br />DOCUMENTATION SECTION<br />DOCUMENTATION SECTION<br />DOCUMENTATION AND RECORDS:<br />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.<br />DOCUMENTS REQUIRED<br />Labels<br />Specifications & testing procedures<br />Specifications for starting & packing materials<br />Specifications for intermediate & bulk products<br />Specifications for finished products<br />Master formulae<br />Packing instructions<br />Batch processing records<br />Batch packaging records<br />Standard operating procedures ( SOPs) & records<br />Miscellaneous<br />All these documents are maintained in the factory according to the legal requirements.<br />1. Master Formula Record:<br />To assure uniformity from batch to batch master formula (master production and control) records for each drug product.<br />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<br />Name and Strength of the product along with dosage form (if it is pharmacopoeial product under trade name, both names will be given)<br />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. <br />A complete list of all the ingredients to be used in the manufacture of the product indicating any special quality characteristics. <br />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).<br />A statement of theoretical weight/measure at appropriate phase of processing.<br />A statement of theoretical yield including permissible limits beyond which investigation is required.<br />A description of containers, closures and packaging materials to be used.<br />A description of all vessels, equipments to be used in their preparation.<br />Processing and packaging procedures.<br />In process controls to be exercised during processing and packaging.<br />Precautions to be taken during manufacture and storage of semi-finished product. <br />2. Batch Manufacturing Records:- <br />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.<br />During the manufacturing information listed below should be recorded, signed and dated by the persons responsible for processing operations:-<br />name of the product<br />batch number<br />date of commencement & completion of significant intermediate stages<br />name of the person responsible for each stage of production<br />initial of operators who carried out significant processes and initial of persons who checked, wherever applicable. <br />Quantity, batch number, quality control report number of each ingredient actually weighed and amount of any recovered material added.<br />In –process controls carried out their results and signature of person who performed.<br />Theoretical yield and actual yield at appropriate stage of production together with explanation. If variation beyond expectation observed.<br />Authorization of any deviation if made.<br />HYGIENE & SANITATION<br />The factory was cleaned every morning with disinfectant and water.<br />Double door system was used in liquid section & capsule section to reduce the level of recontamination.<br />Air curtain installed at the entrance of factory to reduce the dust content on cloths of labor.<br />These were separate change room for men and women. <br />The kitchen of the factory was situated on first floor so as to reduce contamination.<br />Exhaust air, air conditioner, humidity meter were installed of various place in the factory. <br />Fire extinguisher was hanged on the wall of gallery.<br />CHAPTER 9<br />MARKETED PRODUCTS<br />Table:- 11 List of Marketed Product<br />Brand NameContentsPkgZeeclox LB capAmoxycillin 250mg,Cloxacillin 250mg, Lactic Acid Bacillus 1.7 Billion capsuleCaps of 10sZeemox 250 capAmoxycillin 250mg capsuleCaps of 10sZeemox 500 capAmoxycillin 500mg capsuleCaps of 10sPanlee DSRPantaprazole 40mg,Domperidone 30mg sustained release capsuleCaps of 10sRabdom-DRabeprazole 20 mg & Domperidone 10 mg Cap10x10CRabdom-DSRRabeprazole 20 mg & Domperidone 30 mg Cap10x10CDobeflowCalcium Dobesilate Monohydrate BP 500 mg10x10CMaxslim 60Orlistat 60mg Capsules10x10CMaxslim 120Orlistat 120mg Capsul;es10x10CFerest-100 CapNatural Micronised Progesterone10x10CFerest-200 CapNatural Micronised Progesterone10x10CEcorich softulesVitamin E Acetate IP 400mcg & Code liver oil BP 300mgSoftules of 10sLipocinMethylcobalamin,Folic Acid,Vitamins B6 & Alpha Lipoic Acid10x1x10CLycomax-PlusLycopene,LArginine,Betacarotene,Lutein,Vitamins & Minerals10x1x10CPregmax-MPregablin 75mg with Methylcobalamin 750 mcg10x1x10CGabamax-M capGabapentin 300mg & Methylcobalamin 500mcg10x1x10CMaxtil 100Cefpodoxime Proxetil USP 100mg DT Tablet10x10TMaxtil 200Cefpodoxime Proxetil USP 200 mg tablet10x10TRoxime 250 tabCefuroxime Axetil 250 mg tablet10x10TRoxime 500 tabCefuroxime Axetil 500 mg tablet10x10 TCeftis-200Cefixime 200 mg Tablets10x10TMaxflox -200Ofloxacin 200 mg tablet (Alu-Alu)10x10TMaxflox-400Ofloxacin 400 mg tablet (Alu-Alu)10x10TMaxflox-OOfloxacin 200 mg & Ornidazole 500 mg Tab10x10TLevomax 500Levofloxacin 500 mg Tablets (Alu-Alu)10x10TRabrolRabeprazole 20 mg (Alu-Alu)10x10TCitrocalciumAlfacalcidol & Calcium Citrate Tablets10x10TLubrilax TabSodium Picosulphate BP 10mg tablet10x10TSwiftase TabSerratiopeptidase 10mg tablets10x10TSwiftact SDiclofenac50 mg, Serratiopeptidase 10 mg tablets10x10TSwiftact 3DDiclofenac Pottassium 50 mg & Serratiopeptidase 15 mg & Paracetamol 325 mg Tablets10x10TSwiftokDiclofenac Pottassium 50mg, PCM 500mg, Chlorzoxazone 250mg, Magnesium Trisilicate 100 mg Tablets10x10TPetra Plus tabTramadol 50mg,Paracetamol IP 500mg10x10TNimbraNimesulide Tablets25x10TNimbra PlusNimesulide & Paracetamol Tablets25x10THB Rise TabFerrous Ascorbate eq.to elemental iron 100mg,Folic Acid IP 1.5mg Tablet10x10TNovacalAlfacalcidol 0.25mcg & Calcium Citrate 1200mg Tablets10x10TBalaneuron-ForteBenfotiamine,Methylcobalamin Adenosylcobalamin,Folic acid,Pyriodoxine Hydrochloride10x10TZeeclox Kid LB tabAmoxycillin 125mg,Cloxacillin 125mg,Lactic Acid Bacillus 1.7 Billion tabletsTabs of 10sZeemox 250 DTAmoxycillin 250mg Dispersible tabTabs of 10sZeemox CV 625Amoxycillin 500mg, Clavulanic Acid 125mg tabletTabs of 10sZithmax 500 tabAzithromycin 500mg tabletTabs of 10sZeemol 650Paracetamol 650mgTabs of 10sMefmol PlusMefenamic Acid IP 500mg,ParacetamolIP 450mgTabs of 10s<br />CHAPTER 10<br />WORK DONE UNDER PRACTICAL TRAINING<br />WORK DONE UNDER PRACTICAL TRAINING<br />“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 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.<br />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.<br />TABLET :-<br />Brand Name – Mefmol Plus<br />ANTI-INFLAMATORY, ANALGESIC<br />Each uncoated tablet contains:<br />Mefenamic Acid I.P.500 mg<br />Paracetamol I.P. 450 mg<br />Formula for 58,000 tablets:<br /> For 1 tablet, Mefenamic Acid I.P. = 500 mg<br />For 58,000 tablets, Mefenamic Acid I.P. = 500*58,000= 29.0 Kg<br />For 1 tablet Paracetamol I.P. = 450 mg<br />For 58,000 tablets, Paracetamol I.P. = 450*58,000=26.10 Kg<br />Total active ingredients = 55.10 Kg<br />Wt. Of 1 tab. = 1.20 gm <br />Total Wt. = 1.20*58,000=69.6 Kg<br />Lubricants:<br />1) Talc - 2.73%<br />For 58,000 Tablets,<br />(2.73*69.6)/100 = 1.9 Kg.<br /> 2) Magnesium stearate - 1.27%<br /> For 58,000 Tablets,<br /> (1.27*69.6)/100 = .88 Kg.<br />3) Aerosil - 0.907%<br /> For 58,000 Tablets,<br /> (0. 907*69.6/100 = 500 gm<br /> Total lubricants used = 0.63 Kg<br />Disintegrants:<br />Starch - 4.53%<br /> For 58,000 Tablets,<br /> (4.53*69.6)/100 = 3.15 Kg.<br />Binders:<br />1) Starch - 4. %<br /> For 58,000 Tablets,<br /> (4*69.6)/100 = 2.78 Kg.<br />2) Gelatin – 1%<br />For 58,000 Tablets,<br /> (1*69.6)/100 = 0.7 Kg.<br />Moisture content:<br />Moisture - 2 %<br />For 58,000 Tablets,<br /> (2*69.6)/100 = 1.39 Kg.<br />Preservative:<br />Sodium benzoate - 0.0324 %<br />For 58,000 Tablets,<br /> (0.0324*69.6)/100 = 0.02 gm.<br />Diluents:<br />1) Talc - 2.125 Kg.<br />2) Starch - 2.125 Kg.<br /> CHAPTER 10<br />CONCLUSION<br />CONCLUSION<br />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.<br />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.<br />The Q.C. section was well equipped and all the standards and Q.C. Tests were performed according to the official pharmacopoeias very strictly.<br />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.<br />BIBLIOGRAPHY<br />BIBLIOGRAPHY<br />Indian Pharmacopoeia, Government of India, Ministry of Health and Family Welfare, The controller of Publication, 1996, New Delhi.<br />Lachman, L. and Libberman, A. (1991) The Theory and Practice of Industrial Pharmacy, Varghese Publishing House, Bombay.<br />Remington’s – The science and practice of pharmacy, international student edition, 20th ed., 2000 Philadelphia College of Pharmacy and Science, Philadelphia. <br />Ansel’s Pharmaceutical Dosage forms and Drug Delivery Systems’ 8th ed., B.I. Publications Pvt. Ltd., Lippincott Williams and Wilkins, Philadelphia.<br />Bentley’s Text book of Pharmaceutics, 8th ed., Published by All India Traveller Book Seller, Delhi.<br /> Aulton, M. Pharmaceutics – The science of Dosage from Design International Student edition, London. <br />Kohli, D.P.S. and Shah, D.H., Drug formulations, Manual Eastern Publishers, New Delhi.<br />Mithal B.N., ‘Text Book of Pharmaceutical Formulation, Vallabh Prakashan, Delhi.<br />United State Pharmacopoeia, 23rd edition.<br />P.P. Sharma – How to practice GMP (Good Manufacturing Practices) 4th Ed., Vandana Publication Pvt. Ltd., Delhi P.No. 55-57, 215-296<br />