Quality control & Production unit of

Uttar pradesh drugs and pharmaceutical

limited (updpl), lucknow, u.p.

by:Shivendu Ranjan

&Nandita dasgupta

UPDPL, Lucknow,Uttar Pradesh.

FIRM ADDRESS :UTTAR Pradesh Drugs And Pharmaceuticals Limited Lucknow.ADDRESS :- Uttar Pradesh Drugs and Pharmaceutical Co. Ltd.(A Joint Enterprise of Central & U.P. Govt.)A-5, Industrial Area, Kanpur Road Lucknow-226008

LOCATION:- The factory is located in a calm and serene environment of Sarojani Nagar near to Amausi Airport. Which is 10 Kms. away From tehe Charbagh Railway Station, Lucknow.

Introduction

Uttar Pradesh Drugs and Pharmaceutical Co. Ltd. is the only Public sector drug manufacturing company of Uttar Pradesh.

The plant functions as per the WHO/GMP guidelines.

Quality control department in pharmaceutical company is very important . Its role is to analyze quality of raw material, in process and finished products.

List of Products manufactured

by the company

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 mg

10 Furazolidone Tablets IP 100 mg

11 Ibuprofen Tablets IP 200 mg

12 Ibuprofen Tablets IP 400 mg

13 Mebendazole Tablets IP 100 mg

14 Metronidazole Tablets IP 200 mg

15 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 mg

10 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 instruments including, spectrophotometer, dilution test apparatus, disintegration test apparatus, bursting strength apparatus etcTesting of drugs

Tablet – paracetamolCapsule – amoxycillinPowder – ORS

Testing of empty capsules for the presence of any microbesTesting of packaging materials.

microbiology

chemical

Packaging

Q.C. Department is divided in three sections

Standard operating procedures of instruments at quality control chemical department:

Mettler balance Disintegration test apparatus

Polarimeter

Friability test apparatus

Dissolution rate test apparatus

Disintegration test apparatus

Spectrophotometer

Standard operating procedures METTLER BALANCE:

Standard operating procedure Of polarimeter:

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 Indian Pharmacopeia (IP).Following tests were done to found the % purity of active component which should not be less than 95.0% and not more than 105.0% of the stated amount of paracetamol C8H9NO2 :

Identification i.e. Assay of paracetamol Tab. following Indian 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 active component 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 Indian Pharmacopoeia (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 Indian Pharmacopeia 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

Disintegration

microbial limits and loss on drying

For microbial limits : total microbial count should not be more than 1000 per gram of the capsule shells and the capsules are free from the presence of E. coli and Salmonella

THE TOTAL AEROBIC MICROBIAL count was done by plate count method.

For bacteria For fungi

Only two bacterial culture were observed,, Similarly for fungi 3 colonies were observed.

Test for specific micro-organisms was done :

E. Coli (Media used =Mac conkey broth)

Salmonella (Media Used = Xylulose lysine desoxycholate agar )

Since after primary test we got negative result, hence there is absence of salmonella so no need of secondary test.

No Acid formation and No Gas bubble formation after primary 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 •Storage

MATERIALS USED IN PACKAGING ARE:Aluminium foil (thickness- 0.025 ±0.008mm)PVC rigid (thickness-0.25 ± 0.02mm)Polyglycine paperCartonsCaps and closures Tubes and glass bottles Pouches strip packs

Types of Packaging :

1) Strip packaging

2) Blister Packaging

3) Corrugated Box Packaging

4)ORS Packaging

Earlier 4 layer packaging was done – polyglycine paper, polyethene, aluminium foil and polyethene having a dosage of 27.9gm which is now replaced by a three layer packaging –polyester, aluminium foil and polyethene having a dosage of 21.0 gm. The dosage was reduced to decrease the salty taste of ors by decreasing the composition of sodium chloride. The polyester layer prevented moisture penetration as lumps were formed in the 4 layer

packaging.The polyester layer prevented moisture penetration as lumps were formed in the 4 layer packaging.

A tablet is a mixture of active substances and excipients, usually in powder form, pressed or compacted into a solid. The excipients include binders, glidants (flow aids) and lubricants to ensure efficient tabletting; disintegrants to ensure that the tablet breaks up in the digestive tract; sweeteners or flavours to mask the taste of bad-tasting active ingredients; and pigments to make uncoated tablets visually attractive. A coating may be applied to hide the taste of the tablet's components, to make the tablet smoother and easier to swallow, and to make it more resistant to the environment, extending its shelf life.

Advantages and disadvantages

Tablets are easy and convenient to use. They provide an accurately measured dosage in a convenient portable package, and can be designed to protect unstable medications or disguise unpalatable ingredients. Coatings can be coloured or stamped to aid tablet recognition. Manufacturing processes and techniques can provide tablets special properties; for example enteric coatings or sustained release formulations.Tablets cannot be used adequately in case of emergency cases. This is because the rate at which the active ingredient reaches the site to be treated is slow.

ManufacturingIn the tablet-pressing process, it is important that all ingredients be dry, powdered, and of uniform grain size as much as possible. The main guideline in manufacture is to ensure that the appropriate amount of active ingredient is equal in each tablet so ingredients should be well-mixed. Compressed tablets are exerted to great pressure in order to compact the material. If a sufficiently homogenous mix of the components cannot be obtained with simple mixing, the ingredients must be granulated prior to compression to assure an even distribution of the active compound in the final tablet. Two basic techniques are used to prepare powders for granulation into a tablet: wet granulation and dry granulation.Powders that can be mixed well do not require granulation and can be compressed into tablets through Direct Compression

Direct Compression

This method is used when a group of ingredients can be blended and placed in a tablet press to make a tablet without any of the ingredients having to be changed. This is not very common because many tablets have active pharmaceutical ingredients which will not allow for direct compression due to their concentration or the excipients used in formulation are not conducive to direct compression.

Wet granulation

Wet granulation is a process of using a liquid binder or adhesive to the powder mixture. The amount of liquid can be properly managed, and over wetting will cause the granules to be too hard and under wetting will cause the granules to be too soft and friable. Aqueous solutions have the advantage of being safer to deal with than solvents.

Dry granulation

This process is used when the product needed to be granulated may be sensitive to moisture and heat. Dry granulation can be conducted on a press using slugging tooling or on a roller compactor commonly referred to as a chilsonator. Dry granulation equipment offers a wide range of pressure and roll types to attain proper densification. However, the process may require repeated compaction steps to attain the proper granule end point.

TABLETS COATING:The coating in tablets, which is additional step in the manufacturing 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 REMEDY

Unsuitable 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.

Double feed may occur when tablets adhere to the punches or if they are not properly ejected due to incorrect due to incorrect setting of ejectors check the setting of ejectors.

2. DOUBLE FEED:

3. CAPPING: In capping the top or bottom part of the tablet 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 binders

Increase the binder or re-granulate with a 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 Factors

Excessive 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 granules

Unsuitable lubricants Change the lubricants

Mechanical factors

Cam 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 individual ingredient

Separately granulate such 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 design

Use rounded edges.

Mottling is an unequal distribution of colour on a tablet, with light or dark areas standing an otherwise uniform surface. One cause of mottling is a drug whose colour differs from the tablet excipients or a drug whose degradation products are colored. The use of colorants may solve the above problem.

6. MOTTLING:

Capsule

In the manufacture of pharmaceuticals, encapsulation refers to a range of techniques used to enclose medicines in a relatively stable shell known as a capsule, allowing them to, for example, be taken orally or be used as suppositories. The two main types of capsules are hard-shelled capsules, which are normally used for dry, powdered ingredients, and soft-shelled capsules, primarily used for oils and for active ingredients that are dissolved or suspended in oil. Both of these classes of capsule are made both from gelatine and from plant-based gelling substances like carrageenans and modified forms 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 to produce a single-piece gelatin capsule that was sealed with a drop of gelatin 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 form the capsules. Although some companies still use this method, the equipment 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 the capsules, with the filling taking place by blow molding. This method reduced wastage, and was the first process to yield capsules with highly repeatable dosage.

Two-part gel capsules

Two-part hard gelatin capsules

James Murdock patented the two-part telescoping gelatin capsule in London in 1847. Basically, the capsules are made in two parts by dipping metal rods in molten gelatin solution. The capsules are supplied as closed units to the pharmaceutical manufacturer. Before use, the two halves are separated, the capsule is filled with powder (either by placing a compressed slug of powder into one half of the capsule, or by filling one half of the capsule with loose powder) and the other half of the capsule is pressed on. The advantage of inserting a slug of compressed powder is that control of weight variation is better, but the machinery involved is more complex.

Hard Gelatin Capsule Formulation Development

Although hard gelatin capsules are perceived to be a simple dosage form, the design of formulations for the capsules can present significant challenges. The authors have created a prototype hybrid system by linking a decision module (ES) with a prediction module (ANN) capable of yielding formulations of a model BCS Class II drug CAPSULE GEL

CAPSULES PARAMETER AS PER I.P.

Product Dose (m.g.)

Conversion (m.g.)

Drug content

(%)

Dissolution (%)

Amoxicillin 250 285 90-110 80

Ampicillin Trihydrate

250 287 92.5-104.5

75

Cephalexin Monohydrate

250 270 90-110 75

Doxycycline 100 116 90-120

Rifampicine 150 92.5-107.5

PROCESS OF MANUFACTURING CAPSULE

STEP-1Based on production planprepare batch seat and

authenticate from Section Incharge. Make issue indent slip and obtained material from store.

STEP-II. Weighed the material and pass through sieve no.40

STEP-IIITransferred the sieved material in to planetary

mixture, cover it and blend it for 30 minutes.

STEP-VOn receipt of the report from Q.C. transfer the material to

production area.Encapsulate powder on the basis of drug content, reporting

by Q.C. in semi automatic Performa.STEP-VI

Send setting advice to Q.C. for drawing sample on printed Performa. Stored the filling capsule in P.V.C. bag contained in fibers drums. Tie the bags, cover the drums & labeled & keep in quarantine.

STEP-IVSend in process sample to Q.C. for testing of drug under

sample testing active covering particulars of the batch and theoretical average weight. Transfer the bulk of P.V.C. bags contained in fiber drum like the bags cover & label.

Preparation of SYRUP :-

STEP-1Based on the production plan prepare bach sheet and & authentical from section incharge. Make issue indenr sleep to obtain marerial from store.

STEP-2Take dimineralised water (DM) water styeem jacketed kettle and heat to boiling. Weight the sugar & transfer to the boning water with constant stirring. Continue to stirrer until sager dissolving strain though filter filter press using noonan propylene filter into a S.Svessel capacity 1200 lit. Add preservative in D.M eater in 10 lits.S.S bowl. Add dilure acetic acid to make up the syrup ph to 5.5 with contain stirring.

STEP-3(Incorporation of active ingredients.)Prepare aqueous solution of water soluble ingredients by tacking weighed quantity of each separately in small volume of DM water in a 10 lit S.S.bowl.

For dissolving insoluble ingredients use sprit chloform or propylene glycol as mention regalement.

Add these solutions gradually to cooled sugar solution with continious stirring.

Add flavors colors make up the volume with D.M water & stirrer for half an hour. Adjust the Ph between the range given under regalement of the respective product.

STEP-4Filter the bach using filter press.

PREPARATION OF SUGAR SYRUP

Ist Step

INGREDIENTS:-D.M. Water - 200 ltr.P.G.Sugar - 400 KgMethyl Paraben Sodium - 1 KgPropyl Paraben Sodium - 100 GmCitric Acid - 1 Kg.

IInd Step (Soaking of Drug)

INGREDIENTS:-Glycerin - 60 Kg.Sorbitol - 60 KgTrimethoprim - 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 Methyl Cellulose)

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.

CHLORAMPHENICOL SUSPINSION:Batch size – 400 lit1. Chloramphenical Palmitate - 17.360 kg 2. Sod. Citrate - 4.000 kg 3. Citric Acid - 0.400 gm 4. Sod. Saccharin - 0.480 gm 5. Nipagin Sodium - 0.200 gm 6. Nipasol Sodium - 0.200 gm 7. Sod. C.M.C. - 3.000 Kg 8. Sugar - 160.0 kg9. Essence Banana - 1 lit Procedure: D.I. water + sugar + Nipagin Sodium + Nipasol Sodium + Saccharin + citric acid Sod citrate – Solution AD.I. Water + Sod. Carboxy methyl cellulose + Chloramphenical Palmitate- Solution B Add A to B while homogenizing – Solution C Add essence.

Packaging is the science, art and technology of enclosing or protecting products for distribution, storage, sale, and use. Packaging also refers to the process of design, evaluation, and production of packages. Package labelling (BrE) or labeling (AmE) is any written, electronic, or graphic communications on the packaging or on a separate but associated label.Packaging can be described as a coordinated system of preparing goods for transport, warehousing, logistics, sale, and end use. Packaging contains, protects, preserves, transports, informs, and sells. It is fully integrated 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 protection from, among other things, shock, vibration, compression, temperature, etc.

Barrier protection - A barrier from oxygen, water vapor, dust, etc., is often required. Permeation is a critical factor in design. Some packages contain desiccants or Oxygen absorbers to help extend shelf life. Modified atmospheres or controlled atmospheres are also maintained in some food packages. Keeping the contents clean, fresh, and safe for the intended shelf life is a primary function.

Containment or agglomeration - Small objects are typically grouped together in one package for reasons of efficiency. For example, a single box of 1000 pencils requires less physical handling than 1000 single pencils. Liquids, powders, and granules 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 by governments.

Marketing - The packaging and labels can be used by marketers to encourage potential buyers to purchase the product. Package design has been an important and constantly evolving phenomenon for several decades. Marketing communications and graphic design are applied to the surface of the package and (in many cases) the point of sale display.

Convenience - Packages can have features which add convenience in distribution, handling, stacking, display, sale, opening, reclosing, use, and reuse.

Portion control - Single serving or single dosage packaging has a precise amount of contents to control usage. Bulk commodities (such as salt) can be divided into packages that are a more suitable size for individual households. It is also aids the control of inventory: selling sealed one-liter-bottles of milk, rather than having people bring their own bottles to fill themselves.

Packaging machines

A choice of packaging machinery includes, technical capabilities, labor requirements, worker safety, maintainability, serviceability, reliability, ability to integrate into the packaging line, capital cost, floorspace, flexibility (change-over, materials, etc.), energy usage, quality of outgoing packages, qualifications (for food, pharmaceuticals, etc.), throughput, efficiency, productivity, ergonomics, etc.

High speed conveyor with bar code scanner for sorting transport packages

Label printer applicator applying a label to adjacent panels of a 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 oral preparations 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 concentrateBatch No. UV/01/02/03Batch Size 1275 liter

Step 1: Distilled water 800 liter was takenStep 2: Preparation of 20 % cetrimide solutionStep 3: Mixing of tartrazine with chlorhexidine gluconateStep 4: Mixing of IPA and flavoursStep 5: Mixing of distilled water to make 1275 liter

Sunset yellow color citronella oil, Turpinol were used.

UVLON PRODUCT

INGRIDIENTS UVLON (H.C)

UVLON (LOTION)

UVLON (PLUS)

Cetrimide 15%w/v 3%w/v 0.6%w/v

Chlorhexidine gluconate 7.5%w/v 1.5%w/v 0.3%w/v

IPA 6-8%w/v 3-4%w/v 2%w/v

Color Tartrazine Tartrazine sunset yellow

Tartrazine sunset

Flavour Jasmine/terpinol

Jasmine/terpinol Jasmine

PREPERATION OF PHENYL PHELO-PHILL

In Tank -1 saponification of rosin (obtained from pine tree) with 20% Caustic Soda heating was done in steam jacketed tank.

In Tank -2 saponification of castor oil was done by caustic soda also a steamed jacketed tank.In Tank -3 mixing of both the mixtures was done in a tank of 3500 liters capacity with stirrer.

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