1) Doshi Achal Rohitkumar Parul Institute Of Pharmacy, Gujarat University.

Report of the ONE MONTH training : 13 th may’08 - 13 th june’08

Company Name : Elysium Pharmaceuticals Ltd.

Address : Post : Dabhasa, Tal : Padra,

 

Dist : Vadodara, Gujarat - 391 440.

  India.

Phone No : (02662) - 223825 / 223295 / 221555 / 221617 / 221819

Fax No : (02662) - 223513

Email : info@elysiumpharma.com

CERTIFICATE

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This is to certify that this is the original report as per the industrial training undergone by

us for partial fulfillment of B.Pharm as per Gujarat University, Ahmedabad, in The

ELYSIUM PHARMACEUTICALS Ltd. from 13/05/2008 to 13/06/2008. We also certify

that this is an authentic report submitted by us and not duplicated or copied from any

source already available.

Dr. Rajesh K.S.

Principle,

Parul Institute of Pharmacy.

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Acknowledgement

We are grateful to our principal sir, Dr. Rajesh K.S. and Mrs. Anveshna Bhatt for

organizing this industrial training for us.

We are also very much thankful to,

Mr. Y.C.Patel, M.D. of elysium pharma. ltd

Mrs. Jigansha Oza, Q.A. Manger of elysium Pharma Ltd.

They all took out time from their busy schedule to enlighten us on some very

interesting aspects of industry.

The experience has been highly knowledgeable and helped us in understanding

pharmacy from a different perspective. It has definitely enlightened us and shown

us a part that we were unaware of.

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INDEX

1. Introduction & layout of Elusium pharmaceutical 4

2. Products List 6

3. Training schedule 10

4. Brief report on the nature of training under gone department wise 11

5. General scheme for receipt and testing of Raw material 14

6. Flow chart for the processing of Tablets/capsules 21

7. Summary 22

8. Conclusion 23

INTRODUCTION & LAYOUT

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The Company was incorporated as Elysium pharmaceuticalsLtd. in the year 1995 as a formulation unit, situated at

Dabhasa, 19 kms. Away from Vadodara city, Gujarat State, India. The Company commenced its manufacturing

operations in the year 1997. The Company is promoted by Mr. Yashwant Patel in 1995. The Company is involved

in manufacturing of sterile formulations like Liquid and Dry Parenterals, and non-sterile formulations like Tablets,

Capsules, Liquid orals, Ointment, Dry Syrups etc under third party and Contract Manufacturing segment for

established Pharma Companies and Produces its own products Viz.drugs under Ethical segment. Elysium

is committed to maintain and improve the quality of manufactured products to meet customer satisfaction.

The systems and technology are up-graded from time to time, through continuous training & updation. The various

areas of training consist oftechnical as well as general training like quality awareness, communication skills, attitudinal training etc.

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5

PRODUCT LIST

Products Name Name of Active Material Form

EASYPLEX FORTE TAB TabletVitamin A (as Acetate) IP 5000 IU

Vitamin E Acetate IP 25 IU

Ascorbic Acid IP 100mg

Thiamine Mononitrate IP 10mg

Riboflavine IP 10mg

Oyridoxine Hydrochloride IP 3mg

Cyanocobalamin IP 5mcg

Niacinamide IP 50mg

Folic Acid IP 1mg

Calcium Pantothenate IP 12.5 mg

Zinc oxide IP equivalent to:

Elemental zinc15mg

Cupric oxide equivalent to:

Elemental Copper2.5mg

Sodium Selenate euivalent to :

Elemental selenium 60mcg

Manganese Chloride equivalent

to : Elemental manganese1.4mg

Chromium chloride equivalent

to : Elemental chromium65mcg

Excipients q s Colour : Sunset

Yellow FCF  

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EASYPLEX SYR 200ml Syr

EASYPLEX DROPS 15ml Drops

ELCLAVE 1.2gmAmoxicillin 1gm

Clavulanic Acid 200mgInj

ELCLAVE 300gm Amoxicillin 250mg

Clavunic Acid 50mgInj

ELCLAVE 600gm Amoxicillin 500mg

Clavunic Acid 100mgInj

Vit A (as Palmitate) IP 8000 IU

Cholecalciferol IP 100 IU

Vitamin E (As a Tocopheryl

Acetate)Thiam. HydrochlorideIP 0.75mg

Riboflavine Phosphate Sodium IP 1.00mg

Pyridoxine Hydrochloride IP 0.5mg

Cyanocobalamin IP 0.5mcg

D-Panthenol IP 0.5mg

Nicotinamide IP 7.5mg

L-Lysine Monohydrochl. UPS 5mg

Potassium lodide IP 50mcg

Copper Sulphate 100mcg

Copper Sulphate 100mcg

Zinc Sulphate IP 22.2mg

Flavoured syrup base q s  

Vitamin A (as Palmitate) IP 2500 IU

Vitamin E (As a Tocopheryl

Acetate)IP 2.5 IU

Cholecalceferol IP 200 IU

Thiamine Hydrochloride

RiboflavineIP 1mg

Sodium Phosphate IP 1.00mg

Pyridoxine Hydrochl IP 0.5mg

D-Panthenol IP 1mg

Nicotinamide IP 10mg

Ascorbic Acid IP 40mg

L-Lysine Hydrochloride UPS 10mg

Zinc Sulphate IP 13.3mg

Flavoured sorbitol base q s  

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ELCODIN SYR Syr

ELTAX 1 gm Sterile Cefotaxime Sodium IP equiv to Cefotaxime 1gm Inj

ELTAX 250mg Sterile Cefotaxime Sodium IP equiv to Cefotaxime

250mgInj

ELYCET TAB Levoceterizine 5mg Pseudoephedrine Hcl 120mg Tab

ELYCET TAB Aceclofenac 100mg Paracetamol 500mg Tab

ELZONE 1mg Sterile Ceftriaxone Sodium UPS equivalent to Ceftrixone

1gmInj

ELZONE 250mgSterile Ceftriaxone Sodium UPS equivalent to Ceftrixone

250gmInj

FEEL PLUS CAP Cap

Codeine phosphate IP 10mg

Sodium Citrate IP 75mg

Chlorphenramine Maleatel IP 4mg

Menthol IP 1.5mg

Alcohol IP 0.15mg

In a pleasantry flavoured

syrup base Alcohol 3 % v.v.

Ferrous Glycine Sulphate

Zinc Sulphate280mg

Monohydrate UPS 30mg

Folic Acid 5mcg

Selenium (as Sodium selenite)

Histidine Hydrochloride50mg

Monohydrate BP 4mg

Lysine Hydrochloride UPS 25mg

Choline Bitatrate 50mg

Excipients q.s

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FEEL SYR Syr

FRELUNG SYR Syr

NOPIDOL 50 CAP Tramadol Hydrochloride 50mg Water for Injection IP q s Cap

NOPIDOL DP Tramadol 37.5mg+

Paramacetamol 325mg+

Domperidone 10mg Tab

Tab

NOPIDOL 50mg 1ml INJTramadol Hydrochloride 50mg

Water for Injection IP q s

Inj

NOPIDOL 100mg 2ml INJTramadol Hydrochloride 100mg

Water for Injection IP q s

Inj

OMEL RD TabRabiprazole Sodium 20mg

Domperidone 30mg

Tab

SUCRAZEN 200ml SUSP Sucralfate UPS 1gm Susp

Ferrous Amno Citrate IP

75mg(equivalent of 75% of

protein) Vitamin B-12

IP 2.5mcg

Folic Acid IP 0.5mg

Zinc Sulphate IP 35mg

Selenium (as sodium selenate) IP 25mcg

Manganese Sulphate UPS 0.25mcg

Copper Sulphate BP 25mcg

Flavoured syrupy base q.s

Each 10ml contains :

Bromhexine Hydrochl IP 8mg

Dextromethorphan

Hydrobromide

IP 10mg

Ammonium Chloride IP 100mg

(L) Mentol IP 5mg

Flavoured Syrupy base q s

Colours : Brilliant Blue FCF & Tartraxine

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SUCRAZEN-O 100ml SUSPSucralfate USP 1gm

Oxetacaine BP 20mg

Susp

SUCRAZEN CREAMSucralfate USP 7% W/w

Metronidazole IP 1% W/w

Tube

XTRAVIT CAP

Alpha Lipoic Acid USP 200mg, Elcosapentaenoic Acid

90mg, Docosahexaenoic Acid 60mg, Methylcobalamin

1500mcg, Folic Acid IP 1500mcg

Cap

TRAINING SCHEDULE

DATE DEPARTMENT CONTACT TO INCHARGE

13-5-08 to 18-5-08 Parentrals Mr. Nilesh Shah

19-5-08 Liquid Orals Mr.Bharat Patel

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20-5-08 RM/PM/FPS Mr.Vipul Suthar21-5-08 to 23-5-08 Quality Control Mr. M. M. Shah

25-5-08 to13-6-008 Quality Assurance Mr. Thakor Padhiyar

13-6-08 Report Submission to QA Manager

Ms. J. N. Oza

13-6-08 Certification Mr. Jitubhai(Administration)

PARENTRALS13 TH to 18 th of May

Contact person: Mr. Nilesh Shah

Manufacturing Product : 1) Baralgin M 5ml inj.(Metamizol Sodium E.P.) 2) Novalgin 2ml inj. (Analgin)

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3) Deriphylline (Theophyllin + Ectophyllin) 4) Lincolin (quinine HCL)

This unit also operates according to its own S.O.P. The most important feature in this unit is sterility. Care is taken that each and every step involved in the manufacturer of injectables should be free of contamination i.e sterilization is carried out first.

Injectables prepared are Baralgin 5 ml Injection; Novalgin 2ml injection; Deriphyllin 2ml injection To enter into the parenteral area one has to first change clothes…there is a separate uniform for it. One also has to disinfect him or herself with disinfectants such as dettol

First of all decartoning of ampoules takes placeAfter this ampoule washing takes place- 4 washings first with Air, DM water, WFI and then Air. Next is the process of Dry Heat Sterilization which is a 5hr cycle

- 1 hr at 100o C- Sterilization hold time of 2 hrs at 240o C- Cooling at room temperature for 1 ½ hrs

Apart from these processes sterilization of filtration tank (200 litres) by autoclave is also done. Nitrogen flushing of ampoules is also done.

8-STOCK FILLING AND SEALING

6-STOCK WASHING SEALING STERILIZATION FILLING AND

VIAL FILLING AND SEALING

D.H.S. TROLLY

FILTRATIONTANK

PROCESS RAW MATERIAL

DECARTING

LEAK TESTING AND AUTOCLAVE WASHING

CONTAINER

.

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Then ampoule filling and sealing is done and then it goes for visual inspection and finally labeling and packing.

LIQUID ORALS19 th may 08

Contact person : Mr. Bharat patel

Manufacturing Product : Combiflam suspention Syrup AVENTIS Pharmaceuticals (Ibuprofen and paracetamol)

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Suspending agent used : veegum K

1) This also works according to a separate S.O.P

Here liquid dosage forms such as suspensions and syrups are prepared.Eg:- Combiflam suspension and Valparin syrup

There are 2 units in this manufacturing area. In the first area syrup is prepared without active material. The ingredients such as sugar, water ,preservatives are mixed to prepare a syrup in a Bulk manufacturing Tank ( 2000 litres)

From the Manufacturing Tank the preparation goes for Milling (Colloid Mill).From this it goes to the Hopper, at the same time other ingredients such as liquid glucose and fructose and a gum previously soaked in water and stored in a holding tank in case of suspension are added directly into the hopperFrom the hopper it goes to the manufacturing unit where active material along with flavoring and coloring agents are added and mixed thoroughly

The second Unit consists of following through which liquid preparation takes place:-

1) Mini tunnel empty bottle washing machine – Here washing of empty bottles with DM water takes place :- 4 sprays inside and 2 sprays outside

2) Then there is an Empty Bottle Inspection unit3) Filling Tank with 8 syringes ( 35 litres)4) Block filling and sealing machine5) Filled Bottle Inspection Unit for visual inspection6) Labeling and Packing

RM /PM /FPS20-5-08

Contact Person : Mr. Vipul Suthar

2) RM :- Raw Material StorePM :- Packing Material Store

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FPS :-Finished Product Store

All the above three stores work according to S.O.P (Standard Operating Procedure) and cGMP norms are followed

a) RM-

There are various zones through which the raw material passes before it goes for dosage form preparation. The various zones in the RMS are:-

a) Receipt Zone(Receiving Bay)

This is the first zone through which the raw material is receivedGRN(Goods Receipt Note) is prepared.Labelling (Name of RM, Date of Receipt, Quantity received , Batch No., Manufacturer’s Name, Mfg. Date, Expiry Date etc) of RM is checked, RM is also checked for any damages

b) Sampling BoothHere sampling of material takes place under RLAF (Reverse Laminar Air Flow) in presence of QC Chemist—after this RM is labeled SAMPLEDRM is stored in Under Test Area awaiting QC Release demarcated by yellow stringOn Approval from QC- RM is stored under Approved AreaIf Rejected By QC- RM is stored under Rejected AreaFor storing bulk liquids there is a separate store, for flavoring agents, preservatives there is an A.C Store

c) Dispensing Area

Two dispensing zones for RM

1) Dispensing-I-for RM of Tablets, Capsules, Liquid orals2)Dispensing-II-for Parenterals

Dispensing takes place after verification of Material Requisition order (MRO) given by the production department with batch no., batch sizeMaterial issued on FIFO basisFor dispensing of RM the dispensing person should wear proper uniform, gloves, nose mask and proper footwear

RLAF is switched 10 mins prior to dispensingRLAF has 3 filters –HEPA (limit 7-15 mm) , Intermediate Filter (limit 4-6 mm) and Negative pressure (1-4 mm)RLAF takes place in presence of QA chemist

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Each zone in the stories daily checked for maintenance of proper temperature (8-25 oC) humidity(NMT 65 %) and pressure. The stores are cleaned periodically

The S.O.P also mentions about-

Retesting of raw material Handling & Disposal of rejected material Inventory checking Scrap Disposal Maintenance of RLAF. Balances, Cleaning Of AHU, disinfection of various areas

b) PM

(b) The Packing Material Store works in a similar manner as the RM1) The materials stored in this store include:-

1) Primary Material (direct contact with the drug)Eg:- PVC foils, Aluminium foils, Ampoules, Vials,Bottles

2) Secondary MaterialEg:- Cartons, tape roll, boxes, bubbling bag, thermool balls, interlocker, literature.Labels are stored under lock and key

a) FPS

In the FPS the finished dosage forms packed and labelled are stored under appropriate conditions. As and when required the materials are dispatched prior to appropriate notificationFor Export dosage forms there are various norms fulfilled by the pharmaceutical.

QUALITY CONTROLL21-5-08 to 24-5-08

Contact Person : Mr. M. M. shahThis is a very important department in the pharmaceutical.

The various instruments used for quality control of a pharmaceutical are:

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1) HPLC Unit consisting of SPD-10A Shimadzu UV vis detector, LC 10 AT VP Shimadzu Liquid Chromatograph

2) FTIR-8400 S Shimadzu Fourier Transform Infrared Spectrophotometer3) Karl Fischer Titrator-for determining moisture content in material4) Chemiline Photo fluorometer 5) Tablet dissolution tester- for determining the dissolution time of tablet6) Disintegration Tester ED-ZAL 7) Refractometer8) Polarimeter – for determining the optical rotation9) UV-1601 UV Visible Spectrophotometer10)Friabilator USP- for determining surface hardness of tablets11) Bulk Density Apparatus12) Melting and Boiling Point Apparatus13) Ubique- Bursting Strength Apparatus14) pH meter and Conductivity meter15)Brookfield Viscometer16)Autoclave and Hot Air Ovens 17)Titration Equipments18)Analytical balances

QUALITY ASSURANCE25-5-08 to 13-6-08

Contact person : Mr. Thakor PadhiyarQuality Assurance makes sure you are doing the right things, the right way. This department is involved in human resource matters as well as the programming and management of quality assurance operations in design, developing, manufacturing and packaging of pharmaceutical products .It ensures customer satisfaction.

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The works carried out are-

1) Issuance of BMR( Batch Manufacturing Record)

This is the document which consists details of each and every step right from dispensing of raw

material upto its labeling and packing. The details of each and every step is filled by

theconcerned departments and it is the responsibility of the QA chemist to check and verify

whether the various parameters of product manufacturing mentioned in the BMR are fulfilled or

not during its manufacturing at regular intervals of time.

2) Checking parameters during product manufacturing

The various parameter mentioned in the BMR are regularly checked by the QA chemist.For Eg: In case of tablets- parameters checked are –

Humidity and Temperature of various units Weight variation of tablets Friability Hardness Disintegration time Coating Leak Testing Labels and packing- the label should have the correct Batch Number,

Manufacturing Date, Expiry Date, Price.a) There should not be any overprinting on the label.b) The name of the Drug and its details should be clearly visible.c) There should not be any empty space in the strip nor any greasing in the

strip.d) The boxes consisting of cartons of tablets should have proper weight and

packing.

In case of ampoules Visual Inspection is the most important step. The parameters checked in this process are:-

a. Glass particlesb. Fibre particlesc. Black particlesd. Volumee. Shape and size of ampoule

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f. Presence of any sharp edgesg. Cross labeling should not be there

In case of any of above defects in ampoulesor tablets it is rejected and is recorded and the corrective measures are taken.If the defects found are large in number then the whole batch is given for rechecking by the QA chemist

After the verification of all the parameters if appropriate the batch is approved by the QA department and then it goes for sale. At the same time a control of the batch is also kept by the QA department for future reference

TABLET & CAPSULE

TABLETS

Tablets manufactured are Combiflam tablets, Rantac tablets and Nimegesic tablets

The main steps involved in formulation of a tablet are:

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Dispensing and Sieving of ingredients Blending Granulation and Milling Drying Compression Film Coating Packaging

1) Dispensing is the first step in any pharmaceutical manufacturing process. Dispensing is one of the most critical steps in pharmaceutical manufacturing; as during this step, the weight of each ingredient in the mixture is determined according to dose.

The active material is sieved through 20 micron sieve whereas the excipients are sieved through 60micron sieve.

2) Blending is the successful mixing of powders .The powder/granules blending are involved at stage of pre granulation and/or post granulation stage of tablet manufacturing. Each process of mixing has optimum mixing time and mixing speed.It is done with the help of Octangonal Blender.

3) Following particle size reduction and blending, the formulation may be granulated, which provides homogeneity of drug distribution in blend.Granulation is of two types:-

a) Dry granulationb) Wet granulation

4) Drying is a most important step in the formulation and development of pharmaceutical product. It is important to keep the residual moisture low enough to prevent product deterioration and ensure free flowing properties. The commonly used dryer is Fluidized bed dryer

5) After the preparation of granules,they are compressed to get final product. The compression is done by multi station machine

6) Coating is also performed for the following reasons:

1. Maintaining physical or chemical drug integrity 2. Enhancing product acceptance and appearance

The commonly used coatings are Sugar coating and Film coating.

7) The type of packaging will depend on the formulation of the medicine. 'Blister packs' are a common form of packaging used for a wide variety of products.Strip packing is another form of packing.

CAPSULES

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Capsules manufactured are Hostacycline 250/500 mg.

The steps involved in capsule manufacturing are similar to tablets. First of all dispensing and sieving of the raw materials takes place followed by mixing. Empty hard gelatin capsule shells of size 0 are taken.

Then the mixed powder is put in an hopper attached in the capsule filling and locking automatic machine AF 40T.

The machine also has a vaccum system (deduster) to remove the dust of powder that spills on the machine.It also has sensors to separate empty capsule shell from the filled ones and brushes to clean capsule that are often covered with powder.

While this process is on the necessary parameters of the capsule are checked like the weight, locking strength etc.

Finally it goes for packing and labelling.

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Summary

As a summarization, we would like to lay that the industry was truly based on

hard-work and perfection. From our perspective and from what we saw, the industry

made a genuine effort to bring out a good quality of products.

Being a small scale industry it has managed to survived through the high

competition.The instruments used and certain processes were up dated and more of

automated, it could make as much as products of its own and also serve to loan

licensees(or third party contract) of some of the most respected pharma companies

like. SANOFI-AVENTIS,ALEMBIC, ZYDUS SARABHAI , TORRENT etc.

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Conclusion

After completing our training at ELYSIUM PHARMACEUTICALS Ltd. , we will

have to revise our thoughts about the pharmacy. Running a Pharmaceutical Industry is

not only about manufacturing drugs but it also requires technical knowledge,

management & marketing abilities and foresight.

This training proved to be very beneficial for us and it will help us in the better

understanding of our final year subjects.

Lastly, this one month training has proved to be a booster for making a good

Pharmacist from us in the future.

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