FIRM ADDRESS :UTTAR Pradesh Drugs And PharmaceuticalsLimited Lucknow.ADDRESS :-Uttar Pradesh Drugs and Pharmaceutical Co. Ltd.(A Joint Enterprise of Central & U.P. Govt.)A-5, Industrial Area, Kanpur Road Lucknow-226008LOCATION:- The factory is located in a calmand serene environment of Sarojani Nagar near toAmausi Airport. Which is 10 Kms. away Fromtehe Charbagh Railway Station, Lucknow.
IntroductionUttar Pradesh Drugs and Pharmaceutical Co. Ltd. is the onlyPublic sector drug manufacturing company of Uttar Pradesh. The plant functions as per the WHO/GMP guidelines.Quality control department in pharmaceutical company isvery important . Its role is to analyze quality of raw material, inprocess and finished products.
S.N. Tablets 1 Aspirin Tablets IP 300 mg 2 Ascorbic acid Tablets I.P. 500 mg 3 Calcium Lactate Tablets IP 300 mg 4 Chlorpheniramine Maleate Tablets IP 4 mg 5 Ciprofloxacin HCl Tablets IP 250 mg 6 Ciprofloxacin HCl Tablets IP 500 mg 7 Diclofenac Sodium Tablets IP 50 mg 8 Diethyl Carbamazine Citrate Tablets IP 50 mg 9 Diazepam Tablets IP 5 mg10 Furazolidone Tablets IP 100 mg11 Ibuprofen Tablets IP 200 mg12 Ibuprofen Tablets IP 400 mg13 Mebendazole Tablets IP 100 mg14 Metronidazole Tablets IP 200 mg15 Metronidazole Tablets IP 400 mg
S.N. Capsules & Powder 1 Amoxycilline Trihydrate capsules IP 250 mg 2 Amoxycilline Trihydrate capsules IP 500 mg 3 Ampicilline Capsules IP 250 mg 4 Ampicilline Capsules IP 500 mg 5 Cephalexin Capsules IP 250 mg 6 Cephalexin Capsules IP 500 mg 7 Doxycycline Hydrochloride capsules IP 100 mg 8 Tetracycline capsules IP 250 mg 9 Tetracycline capsules IP 500 mg10 Oral Rehydration Salt citrate 2709g IP
S.N. Liquid, External Preparation & Disinfectants 1 Trimethoprim & Sulphamethoxazole oral suspension IP 2 Paracetamol Syrup IP 3 Povidone–iodine Solution IP 4 Benzyl Benzoate Application IP 5 Piperazine Citrate Syrup IP 6 UVLON (Hospital Concentrate) 7 FLO-PHIL (THE PHENYL) 8 Nitrofurazone Ointment 0.2% w/w
Objective:Following are the contents of the report :Standard operating procedures of various instrumentsincluding, spectrophotometer, dilution test apparatus,disintegration test apparatus, bursting strength apparatus etcTesting of drugs Tablet – paracetamol Capsule – amoxycillin Powder – ORSTesting of empty capsules for the presence of any microbesTesting of packaging materials.
Q.C. Department is divided in three sections Packaging chemical microbiology
Standard operating procedures of instruments at quality control chemical department: Mettler balance Disintegration test Polarimeter apparatus Friability test Dissolution rate test Disintegration test apparatus apparatus apparatus Spectrophotometer
Standard operating procedures METTLER BALANCE:
Standard operating procedure Of double beam mass spectrophotometer:
Standard operating procedure Of dissolution rate test apparatus:
Standard operating procedure Of friability test apparatus:
Standard operating procedure Of Disintegration test apparatus:
Testing of paracetamol tablets:Testing of all the drugs were according to the IndianPharmacopeia (IP).Following tests were done to found the %purity of active component which should not be less than95.0% and not more than 105.0% of the stated amount ofparacetamol C8H9NO2 : Identification i.e. Assay of paracetamol Tab. followingIndian Pharmacopoeia (I.P.) Disintegration test for paracetamol Tab. Following I.P. Dissolution of Paracetamol Tab. Following I.P. Uniformity of weight following I.P.
Testing of Amoxycillin capsules:Following tests were done to found the % purity of activecomponent which should not be 90.0% and not more than 110.0%of the stated amount of C16H19N3O5S:Identification i.e. Assay of Amoxycillin Cap. following IndianPharmacopoeia (I.P.) Disintegration test for Amoxycillin Cap. Following I.P. Dissolution test for Amoxycillin Cap. Following I.P. Uniformity of weight test for Amoxycillin Cap. following I.P.
Testing of Oral rehydration salt :Following Test have been performed for Q.C. of O.R.S. Powder : Uniformity of weight for O.R.S. powder following IndianPharmacopeia Dissolution test for O.R.S. Salt following I.P. Disintegration test for O.R.S. Salt following I.P.
Standard operating procedures of instruments at quality control MICROBIOLOGY DEPARTMENT:Autoclave Short OK Strip BOD Incubator
Testing of empty capsulesTesting of empty capsules include –Odour Identification Labelling Average weight Disintegrationmicrobial limits and loss on dryingFor microbial limits : total microbial count should not be morethan 1000 per gram of the capsule shells and the capsules arefree from the presence of E. coli and Salmonella
THE TOTAL AEROBIC MICROBIAL count was done by plate count method. For bacteria For fungiOnly two bacterial culture were observed,, Similarly for fungi3 colonies were observed.
Test for specific micro-organisms was done : E. Coli (Media Salmonella (Media Used = Xylulose used =Mac lysine desoxycholate agar ) conkey broth)No Acid formation andNo Gas bubble formationafter primary test. Since after primary test we got negative result, hence there is absence of salmonella so no need of secondary test.
Standard operating procedures of instruments at quality control PACKAGING INSTUMENT:
NEED FOR PACKAGING:•Enhanced durability•Moisture / oxygen sensitivity•High temperature sensitivity•Conflicting barrier / sterilization requirements•StorageMATERIALS USED IN PACKAGING ARE:Aluminium foil (thickness- 0.025 ±0.008mm)PVC rigid (thickness-0.25 ± 0.02mm)Polyglycine paperCartonsCaps and closuresTubes and glass bottlesPouchesstrip packs
4)ORS PackagingEarlier 4 layer packaging was done – polyglycine paper, polyethene,aluminium foil and polyethene having a dosage of 27.9gm which is nowreplaced by a three layer packaging –polyester, aluminium foil and polyethenehaving a dosage of 21.0 gm. The dosage was reduced to decrease the saltytaste of ors by decreasing the composition of sodium chloride. The polyesterlayer prevented moisture penetration as lumps were formed in the 4 layerpackaging.The polyester layer prevented moisture penetration as lumps wereformed in the 4 layer packaging.
A tablet is a mixture of active substances andexcipients, usually in powder form, pressed orcompacted into a solid. The excipients includebinders, glidants (flow aids) and lubricants toensure efficient tabletting; disintegrants to ensurethat the tablet breaks up in the digestive tract;sweeteners or flavours to mask the taste of bad-tasting active ingredients; and pigments to makeuncoated tablets visually attractive. A coating maybe applied to hide the taste of the tabletscomponents, to make the tablet smoother andeasier to swallow, and to make it more resistant tothe environment, extending its shelf life.
Advantages and disadvantagesTablets are easy and convenient to use. They provide anaccurately measured dosage in a convenient portablepackage, and can be designed to protect unstablemedications or disguise unpalatable ingredients. Coatingscan be coloured or stamped to aid tablet recognition.Manufacturing processes and techniques can providetablets special properties; for example enteric coatings orsustained release formulations.Tablets cannot be used adequately in case of emergencycases. This is because the rate at which the activeingredient reaches the site to be treated is slow.
ManufacturingIn the tablet-pressing process, it is important that all ingredients bedry, powdered, and of uniform grain size as much as possible. Themain guideline in manufacture is to ensure that the appropriateamount of active ingredient is equal in each tablet so ingredientsshould be well-mixed. Compressed tablets are exerted to greatpressure in order to compact the material. If a sufficientlyhomogenous mix of the components cannot be obtained with simplemixing, the ingredients must be granulated prior to compression toassure an even distribution of the active compound in the final tablet.Two basic techniques are used to prepare powders for granulation intoa tablet: wet granulation and dry granulation.Powders that can be mixed well do not require granulation and can becompressed into tablets through Direct Compression
Direct CompressionThis method is used when a group of ingredientscan be blended and placed in a tablet press tomake a tablet without any of the ingredientshaving to be changed. This is not very commonbecause many tablets have active pharmaceuticalingredients which will not allow for directcompression due to their concentration or theexcipients used in formulation are not conduciveto direct compression.
Wet granulationWet granulation is a process of using aliquid binder or adhesive to the powdermixture. The amount of liquid can beproperly managed, and over wetting willcause the granules to be too hard and underwetting will cause the granules to be toosoft and friable. Aqueous solutions havethe advantage of being safer to deal withthan solvents.
Dry granulationThis process is used when the product needed to begranulated may be sensitive to moisture and heat.Dry granulation can be conducted on a press usingslugging tooling or on a roller compactorcommonly referred to as a chilsonator. Drygranulation equipment offers a wide range ofpressure and roll types to attain properdensification. However, the process may requirerepeated compaction steps to attain the propergranule end point.
TABLETS COATING:The coating in tablets, which is additional step in themanufacturing process.OBJECTIVES: •To makes the taste, odor, or color of the drug: •To provide physical and chemical protection for the drug •To control the release of the drug from the tablet. •To protect the drug from the gastric environment of the stomach with an acid resistant enteric coating.
The tablet pressing operation an old Cadmach rotary tablet press
Different Views of old Cadmach rotary tablet press
SOME COMMON PROBLEMS IN TABLETING: 1. WEIGHT FLUCTUATIONS: REASON REMEDYUnsuitable granule size Change the granule size, usually small granules are for smaller tablets.Granule shape Prepare as round granules as possible to avoid uneven air spaces.Powder content The proportion of the fine powder should be kept below 20% of granulate.Volume differential The filling volume in the die should be near as possible to the loose volume density.
Flow Control Lubricants- Choice and quantity may be changed to control the flow of granules usually 1-5% are sufficient.Electrostatic charging This can be eliminated by spraying the granules with water in order to increase their conductivity so that the electricity is conducted t0 the surrounding machine parts and earthed.Humidity If the granulate is too wet Re-dry the granules.
2. DOUBLE FEED:Double feed may occur when tabletsadhere to the punches or if they are notproperly ejected due to incorrect dueto incorrect setting of ejectors checkthe setting of ejectors.
In capping the top or bottom part of the tablet3. CAPPING: separates from the main body completely are partially.Insufficient moisture Spray the granules with water or water glycerin mixture.Excessive moisture Re-dry the granules.Insufficient binders unsuitable Increase the binder or re-granulate with abinders more suitable binder.Excess air in granulate Adjust the relative punch travels to compress in upper part of the die or use tapered dies.Excess powder content Sift out the fine powder or regranulate with different binders.Mechanical FactorsExcessive pressure Reduce the compression speed.Insufficient air escape Use tapered dies. Compression should take place in upper part of before actual compression.
4. CRACKING:Excess moisture in granulate Re-dry the granulesUnsuitable lubricants Change the lubricantsMechanical factorsCam tolerance exceeded Repair or replace the cam.Incorrect fitting of punches Recheck
5. STICKING: Adherence of granules to die walls is referred to as ‘sticking’ Excessive humidity Dry the granules and or air condition the room. Low melting point of Separately granulate such individual ingredient ingredients. Insufficient cohesion Slowly raise the compression pressure Excess powders Sift out excess powders Insufficient lubrication Increase or change the lubricant Dies and punches dull Polish the dies and punches. Defective engraving Use rounded edges. design
6. MOTTLING:Mottling is an unequal distribution of colouron a tablet, with light or dark areas standingan otherwise uniform surface. One cause ofmottling is a drug whose colour differs fromthe tablet excipients or a drug whosedegradation products are colored. The use ofcolorants may solve the above problem.
CapsuleIn the manufacture of pharmaceuticals, encapsulation refers to arange of techniques used to enclose medicines in a relatively stableshell known as a capsule, allowing them to, for example, be takenorally or be used as suppositories. The two main types of capsulesare hard-shelled capsules, which are normally used for dry,powdered ingredients, and soft-shelled capsules, primarily used foroils and for active ingredients that are dissolved or suspended in oil.Both of these classes of capsule are made both from gelatine andfrom plant-based gelling substances like carrageenans and modifiedforms of starch and cellulose.
Soft gel encapsulation Cod liver oil soft gel capsules.In 1834, Mothes and Dublanc were granted a patent for a method toproduce a single-piece gelatin capsule that was sealed with a drop ofgelatin solution. They used individual iron moulds for their process,filling the capsules individually with a medicine dropper. Later on,methods were developed that used sets of plates with pockets to formthe capsules. Although some companies still use this method, theequipment is not produced commercially any more. All modern soft-gel encapsulation uses variations of a process developed by R.P.Scherer in 1933. His innovation was to use a rotary die to produce thecapsules, with the filling taking place by blow molding. This methodreduced wastage, and was the first process to yield capsules withhighly repeatable dosage.
Two-part gel capsules Two-part hard gelatin capsulesJames Murdock patented the two-part telescoping gelatin capsule inLondon in 1847. Basically, the capsules are made in two parts bydipping metal rods in molten gelatin solution. The capsules aresupplied as closed units to the pharmaceutical manufacturer. Beforeuse, the two halves are separated, the capsule is filled with powder(either by placing a compressed slug of powder into one half of thecapsule, or by filling one half of the capsule with loose powder) andthe other half of the capsule is pressed on. The advantage of insertinga slug of compressed powder is that control of weight variation isbetter, but the machinery involved is more complex.
Hard Gelatin Capsule Formulation DevelopmentAlthough hard gelatin capsules are perceived tobe a simple dosage form, the design offormulations for the capsules can presentsignificant challenges. The authors have created aprototype hybrid system by linking a decisionmodule (ES) with a prediction module (ANN)capable of yielding formulations of a model BCSClass II drug CAPSULE GEL
PROCESS OF MANUFACTURING CAPSULESTEP-1 Based on production planprepare batch seat andauthenticate from Section Incharge. Make issue indent slip and obtained material from store.STEP-II. Weighed the material and pass through sieve no.40STEP-III Transferred the sieved material in to planetarymixture, cover it and blend it for 30 minutes.
STEP-IV Send in process sample to Q.C. for testing of drug undersample testing active covering particulars of the batch andtheoretical average weight. Transfer the bulk of P.V.C. bagscontained in fiber drum like the bags cover & label.STEP-V On receipt of the report from Q.C. transfer the material toproduction area. Encapsulate powder on the basis of drug content, reportingby Q.C. in semi automatic Performa.STEP-VI Send setting advice to Q.C. for drawing sample on printedPerforma. Stored the filling capsule in P.V.C. bag contained infibers drums. Tie the bags, cover the drums & labeled & keep inquarantine.
Preparation of SYRUP :-STEP-1Based on the production plan prepare bach sheet and &authentical from section incharge. Make issue indenr sleep toobtain marerial from store.STEP-2Take dimineralised water (DM) water styeem jacketed kettle andheat to boiling. Weight the sugar & transfer to the boning waterwith constant stirring. Continue to stirrer until sager dissolvingstrain though filter filter press using noonan propylene filter intoa S.Svessel capacity 1200 lit. Add preservative in D.M eater in 10lits.S.S bowl. Add dilure acetic acid to make up the syrup ph to5.5 with contain stirring.
STEP-3(Incorporation of active ingredients.)Prepare aqueous solution of water soluble ingredients by tackingweighed quantity of each separately in small volume of DM waterin a 10 lit S.S.bowl.For dissolving insoluble ingredients use sprit chloform orpropylene glycol as mention regalement.Add these solutions gradually to cooled sugar solution withcontinious stirring.Add flavors colors make up the volume with D.M water & stirrerfor half an hour. Adjust the Ph between the range given underregalement of the respective product.STEP-4Filter the bach using filter press.
PREPARATION OF SUGAR SYRUPIst StepINGREDIENTS:- D.M. Water - 200 ltr. P.G.Sugar - 400 Kg Methyl Paraben Sodium - 1 Kg Propyl Paraben Sodium - 100 Gm Citric Acid - 1 Kg.
IInd Step (Soaking of Drug)INGREDIENTS:- Glycerin - 60 Kg. Sorbitol - 60 Kg Trimethoprim - 8 Kg. Sulfamethoxazole - 40 Kg. Twin 80 - 02 Kg.The above composition is passed thought 60-80 mesh sieve to provide a good suspension.The PH is adjusted between 4 – 5.5
IIIrd Step (Soaking of Carboxy MethylCellulose)INGREDIENTS:- D.M.Water - 150 Kg. Sunset Yellow - 50 Gm. Methyl Paraben Sodium - 1 Kg. Propyl Paraben Sodium - 100 Gm. Carboxy Methyl Celluclose - 5.5 Kg.
Packaging is the science, art and technology of enclosingor protecting products for distribution, storage, sale, anduse. Packaging also refers to the process of design,evaluation, and production of packages. Packagelabelling (BrE) or labeling (AmE) is any written,electronic, or graphic communications on the packagingor on a separate but associated label.Packaging can be described as a coordinated system ofpreparing goods for transport, warehousing, logistics,sale, and end use. Packaging contains, protects,preserves, transports, informs, and sells. It is fullyintegrated into government, business, institutional,industry, and personal use.
The purposes of packaging and package labelsPackaging and package labelling have several objectives:Physical protection - The objects enclosed in the package may require protectionfrom, among other things, shock, vibration, compression, temperature, etc.Barrier protection - A barrier from oxygen, water vapor, dust, etc., is oftenrequired. Permeation is a critical factor in design. Some packages containdesiccants or Oxygen absorbers to help extend shelf life. Modified atmospheresor controlled atmospheres are also maintained in some food packages. Keepingthe contents clean, fresh, and safe for the intended shelf life is a primary function.Containment or agglomeration - Small objects are typically grouped together inone package for reasons of efficiency. For example, a single box of 1000 pencilsrequires less physical handling than 1000 single pencils. Liquids, powders, andgranules need containment.Information transmission - Packages and labels communicate how to use,transport, recycle, or dispose of the package or product. With pharmaceuticals,food, medical, and chemical products, some types of information are required bygovernments.
Marketing - The packaging and labels can be used by marketers toencourage potential buyers to purchase the product. Packagedesign has been an important and constantly evolvingphenomenon for several decades. Marketing communications andgraphic design are applied to the surface of the package and (inmany cases) the point of sale display.Convenience - Packages can have features which add conveniencein distribution, handling, stacking, display, sale, opening,reclosing, use, and reuse.Portion control - Single serving or single dosage packaging has aprecise amount of contents to control usage. Bulk commodities(such as salt) can be divided into packages that are a more suitablesize for individual households. It is also aids the control ofinventory: selling sealed one-liter-bottles of milk, rather thanhaving people bring their own bottles to fill themselves.
Packaging machinesA choice of packaging machinery includes, technical capabilities, laborrequirements, worker safety, maintainability, serviceability, reliability, ability tointegrate into the packaging line, capital cost, floorspace, flexibility (change-over,materials, etc.), energy usage, quality of outgoing packages, qualifications (forfood, pharmaceuticals, etc.), throughput, efficiency, productivity, ergonomics, etc. High speed conveyor with bar Label printer applicator applying a code scanner for sorting transport label to adjacent panels of a packages corrugated box.
Packaging machines may be of the following general types:• Blister packs, skin packs and Vacuum Packaging Machines• Bottle caps equipment, Over-Capping, Lidding, Closing, Seaming and Sealing Machines• Cartoning Machines• Box, Case and Tray Forming, Packing, Unpacking, Closing and Sealing Machines• Cleaning, Sterilizing, Cooling and Drying Machines• Conveyors, Accumulating and Related Machines• Feeding, Orienting, Placing and Related Machines• Filling Machines: handling liquid and powdered products• Package Filling and Closing Machines• Form, Fill and Seal Machines• Inspecting, Detecting and Checkweigher Machines• Palletizing, Depalletizing, Unit load assembly• Product Identification: labeling, marking, etc.• Wrapping Machines• Converting Machines• Other speciality machinery: slitters, perforating, laser cutters, parts attachment, etc
PHENYL SECTION is totally separate section from where oralpreparations are manufactured .section has large area which has – 1.Two steamed jacketed tank for saponification of rosin and caster oil. 2. Two mixing tank. Steps involved in preparation of uvlon hospital concentrate Batch No. UV/01/02/03 Batch Size 1275 liter Step 1: Distilled water 800 liter was taken Step 2: Preparation of 20 % cetrimide solution Step 3: Mixing of tartrazine with chlorhexidine gluconate Step 4: Mixing of IPA and flavours Step 5: Mixing of distilled water to make 1275 liter Sunset yellow color citronella oil, Turpinol were used.
PREPERATION OF PHENYL PHELO-PHILLIn Tank -1 saponification of rosin (obtained frompine tree) with 20% Caustic Soda heating was donein steam jacketed tank.In Tank -2 saponification of castor oil was done bycaustic soda also a steamed jacketed tank.In Tank -3 mixing of both the mixtures was done ina tank of 3500 liters capacity with stirrer.