Kamlesh traning report

PREFACE

This training report highlights the techniques and procedures studied and performed in
the QA/QC department of Lupin Ltd.Mandideep.the student of VNS Institute of
Pharmacy.(Affiliated to Rajiv Gandhi Prodyogiki Vishwavidhalaya) undergoes a one
month traing programme to enhance his skill and knowledge. Thus it helps to understand
the industrial application of various theoretical aspects of Pharmacy.

Lupin product reach more than 50 countries with significant presence in besides
India,Russia,US,Kazhakistan and China.

The lupin plant at Mandideep manufactures both APIs and finished dosages.

SOFTOVAC
FIBRIL
SOFTOVAC SF
FIBRIL SF

AKNOWLEDGEMENT

i wish to express my sincere thanks to those who helped me to develop this project report.

at first i extend my thanks to Mr.C.A.Nair (personel and administration manager) for giving me
this oppourtunity to complete my industrial training in LUPIN LTD.

i express my sincere indebtness and profound sense of gratitute to my project guide Mr.Johnson
MJ for their untiring labour and generous efforts which enabled me layout the work of this project.

i am also thankful to Mr.Ajit Jaiswal and Mr.Praveen Kumar Sahu for their valuable suggestion,
constant encouragement, overwhelming help and cooperation.

This project would never have taken this shape without the parenteral care watchful help of Mr.Jai
Devan and other staff members of LUPIN LTD.

with immerse pride and deep gratitute for which i am left with no word.

i express my indebtness to my principal Mr.S.K.Yadav and training and placement officer

Mr.Vipender Khatik for their valuable guidance, readiness and inspiration.

Finally, i have no reservation in admitting that it was nothing else but the grace of God that
enabled me to achieve this seemingly invisible task.

CONTENTS
 1. INDUSTRIAL PROFILE
2. QUALITY POLICY OF LUPIN
3. QUALITY ASSURANCE
4. QUALITY CONTROL
5. ABOUT THE PRODUCTS
6. INSTRUMENTS USED IN QA/QC LAB
7. PRODUCTION DEPARTMENT
8. INTRUMENTS USED IN FORMULATION
9. GENERAL TESTS OF SOFTOVAC
10. LIMIT TESTS PROCEDURE FOR ANALYSIS OF SOFTOVAC
11. MANUFACTURING OF SOFTOVAC
12. CONCLUSION

INTRODUCTION

LUPIN is multidivisional and multilocational organization.the company was founded in

1972.it has presence in pharmaceutical formulations like bulk drugs,herbal drugs
andbiotecnology based products.the specialities include antituberculor
drugs,cephalosporin, cardiovascular drugs.lupin has its manufacturing activities located
as Ankleshwar in Gujrat,Aurangabad,Tarapur in Maharashtra and Mandideep in M.P.

Lupin and its pharma and R$D facility,generic research of API,new chemical
entities,research facilities at Pune,Lupin Ltd. Mandideep has pharmaceutical formulation
and bulk plants located at 198-202,New Industrial Area no.2,
Mandideep,distt:Raisen(M.P.)

Lupin (pharma plant II ) is located at 211,New Industrial Area no.2, Mandideep on a

23774 sq.m.plot. the facilities include raw and packaging material warehouses.it also has
finished goods, warehouses and full fledged utilities section. All testing of
raw,intermediate and finished goods is done in a well equipped self sufficient quality
control laboratory.

The company has about 3000 employees on its roll for all the sites put together. the total
area is allocated for the following functions-

-manufacturing
-quality assurance
-warehouse
-utilities
-administration and canteen

QUALITY POLICY OF LUPIN

 • The company shall estabilish and maintain high standards of quality of its
products manufactured at various locations.

• Product shall be manufactured and marketed meeting all quality parameters

related to identity,purity,safety and efficacy through well defined quality
assurance and validation systems.

• Company shall comply with current, national and international regulations as

applicable and continuously move towards meetin stringent global standards.

• Continuous training shall be given to the employees in organization to enhance

their skill in performing their organized tasks.

QUALITY ASSURANCE

The quality assurance department (QED) has the responsibility and authority to define
norms and regulations for various activities including personel training,sanitization and
cleaning of general areas. Quality assurance department rewiews the production records
to ensure that all manufacturing operations are carried out as per the laid down
instruction.

The QA department is assigned to the following responsibilities_

• Evaluation and approval of all validation protocols.

• Specific sampling procedures.
• Evaluation and approval of all validation protocols.
• Rewiew and approval of BPRs prior to the release of goods for distribution to
ensure compliance to GMP during the manufacturing of any batch.
• Audit and approval of vendors and contract manufacturers.
• Evaluation and analysis of market complaints and batch recall.
• Routine finished product stability.

GOODS MANUFACTURING PRACTICES

Quality assuarance department ensures that_

• All production facilities are provided to meet cGMP requirements and adequately
trained and quality person for carrying out the operation.
 • All manufacturing operations are clearly designed and checked routinely to
confirm the quality of finished products.

IN PROCESS QUALITY ASSURANCE

Quality assuarance is responsible for in process controls at all critical stages of

manufacturing. Separate IPQC lab is provided inside the plant to carry out the routine
process tests by qualified persons.

FINISHED PRODUCT RELEASE

After the completion of labelling and packing operation, finished goods are transferred to
inhouse quarantine area, on completion of testing and final inspection of finished
goods,the batch records are sent to quality assurance for rewiew. On satisfactory
compliance the quality assurance/ quality control department shall issue release note for
further distribution.

QUALITY CONTROL

the quality control department is part of quality assurance department.it is the department of
pharmaceutical industry which deals with the control of quality of raw materials are manufactured
product. the major activities of Quality control department are:-

- sampling and testing of raw and packaging materials.

- sampling and testing of inprocess materials
- sampling and testing of finished products
- carrying out stability studies
- testing of water samples
- microbiological monitoring
- calibration of instruments
- qualification of working standards

GOODS MANUFACTURING PROCESS

It is responsible for approving or rejecting the raw materials,packing materials and finished
manufactured,process,packed or label by the company.

the company follows ths specifications and test methods as per IP/BP/USP for raw materials and
finished products.the company has also additional in-house laid down specifications for testing of
finished products and raw materials,which are stringent than the pharmacopoeial limits for better
control on quality of products.

Quality control department has following two sections_

1.For raw materials and manufactured drugs.

2.packaging material quality.
(1)FOR MANUFACTURE AND RAW MATERIALS

it consists of following department-

• Intrumental analysis
• Microbiological section
• Documentation section

INSTRUMENTATION ANALYSIS

it is a part of QC department in responsible person recieve the sample of manufactured drugs

from batch and check the quality of product by using instrument. In this section responsible
person check the quality of powder by comparing standard reference.

MICROBIOLOGICAL SECTION

It is second part of QC,it detects the biological load present in the drug.

DOCUMENTATION SECTION

it is the main department of QC where all records,files and reports are stored and maintained by a
responsible person.this department perforns following functions_

-maintains and store records like calibration records,SOPs,GMPs etc.

-maintains guidelines
-verification of records

(A) FOR RAW MATERIALS

recieve the sample from RM store

check the quality by performing various tests

if pass, then transfer to manufacturing department, if fail, then reject.

(B) FOR MANUFACTURED DRUGS

recieve the sample of manufactured drugs from production department

check the quality by perforning various tests

if pass, then the batch is approved,if fail,then reject

(2) PACKAGING MATERIAL QUALITY CONTROL

it deals with quality control of various packaging materials.it checks the following parameters_

-batch no
-printing quality
-thickness of aluminium foil
-width of material
-size of label
-adhesive quality
-colour scheme.

Packaging material recieved by PM store

Testing in QC

Approved

Packaging department

PRODUCTS

1. SOFTOVAC
2. SOFTOVAC SF
3. FIBRIL
4. FIBRIL SF

INSTRUMENTS USED IN QA/QC LAB

• MELTING POINT APPARATUS

• BURSTING STRENGTH TESTER
• BULK DENSITY APPARATUS
• TABLET DISSOLUTION APPARATUS
• DISINTEGRATION TESTER
• CYCLOMIXER
• DIGITAL PH METER
• MOISTURE BALANCE
• ANALYTICAL BALANCE
• FOURIER TRANSMISSION INFRA RED SPECTROMETER
• UV VISIBLE SPECTROPHOTOMETER
• INCUBATOR
• DRYING OVEN
• FUMING CHAMBER
• WATER BATH
• AUTOCLAVE
• VACCUM OVEN
• DRY HEAT STERILIZER
• MUFFLE FURNANCE

PRODUCTION DEPARTMENT

INGREDIENTS

SOFTOVAC

isabgol (plantago ovata) husk

sonamukhi (senna)
amaltas (cassia fistula)
terminellia chebula (hard)

liquorice (mulethi)
rose petals (gulab dal)
fennel seeds (saunf)
sugar (sharkara)
sodium benzoate

DOSAGE

adult : 5-10 gm
children : 2.5-5.0 gm

MECHANISM OF ACTION

FIBRIL : isabgula husk 3.4g/11gm

SOFTOVAC : each 5 gm provides isabgol husk 2 gm

BULK FORMING AGENTS

ISABGULA

mechanism of action :- it contains natural colloidal mucilage which forms a gelatinus mass by
absorbing water, thus softening and facilitating colonic transit of stool.

indications :- functional constipation, constipation with IBS

dosage :- adults : 5-10 gm of husk mixed with water or milk at bed time.
children :not recommended

contraindications : history of peptic ulcers, subacute or acute intestinal obstruction, avoid in

patients with undiagnosed abdominal pain or vomiting,
abdominal malignancy and in constipation due to hypothyroidism or drug induced constipation.

status in :-
pregnancy : contraindicated
lactation : use with caution
old age : use with caution
children : not recommended

INTRUMENTS USED IN FORMULATION

• FLUIDISED BED DRYER

• OCTAGONAL BLENDOR
• MECHANICAL SIFTER
• HYDRAULLIC LIFT
• PLANETORY MIXER
• FILLING MACHINE
• SCREW CAPPING MACHINE
• INDUCTION SEALING MACHINE
• WEIGHING MACHINE
• IN PROCESS CONTAINORS
• INTERMEDIATE PRODUCT CONTAINERS

GENERAL TEST PROCEDURE FOR THE ANALYSIS OF SOFTOVAC

Description/appearance

It helps in the preliminary evaluation of an article.

Procedure
1. Visually check the product liquid or solid dosage forms with unaided eyes.
2. Check the following whether the material is liquid or solid.
3. Colour of material.
4. Odour/Odourless

Loss on drying (LOD):- Loss on drying is the loss in weight in %w/w resulting from
water and volatile matter of any kind can bedriven of under specified conditions.

Apparatus:-

1. LOD bottles with glass stoppers.

2. Electric oven.
3. Dessicators with silica gel.
4. A calibrated balance with thermometer.

Procedure-

1. weigh accurately 1g of the sample in previously dried and weighed LOD

bottle.
2. put the bottle in an electric oven under specified conditions along with the
glass stopper in open condition .
3. after drying is completed weigh it and calculate the LOD of the sample under
study by:-
LOD%=(A-B)/B*100
Where,
A is wt. of sample in gm taken for LOD.
B is wt. of sample in gm after drying.
RESIDUE ON IGNITION (SULPHATED ASH):-

Sulphated ash determines the inorganic impurities present in the substance by

incinerating the substances with the aid of sulphuric acid at 600+ or – 50c.

Apparatus:-
1. silica or platinum crucible.
2. muffle furnace.
3. calibrated balance.
4. desicators.

Procedure-

1. weigh 1g of the sample in a previously dried and weighed crucible.

2. moisten the sample with small amount of sulphuric acid (1ml) and heat
gently until the sample is thoroughly charred.
3. cool, moisten the residue again with a small amount of sulphuric acid, heat
gently until white fumes are no longer evolved.
4. ignite at 60+ or -50c in a muffle furnace until the residue is completely
incinerated.
5. cool the crucible in a dessicator and weigh it.
6. calculate the % residue let out in the crucible.

Residue on ignition;
(%w/w)=B/A*100
where,
A is wt. of the residue in gm.
B is wt. of the sample in gm.

TOTAL ASH

Total ash determines the inorganic impurities present in the substance by

incinerating the substance at 600+ or – 25c.

Apparatus-
1. Silica/Platinum crucible
2. A calibrated balance.
3. A dessicator.

Procedure-
1. Weigh 1g of the sample in a previously weighed crucible.
2. Place the crucible in a muffle furnace maintained at 600+ or -25c for at least 2hrs.
4. Cool the crucible to room temperature in a dessicator and weigh it.
5. Calculate the weight of residue left out in the crucible.

Total ash (%w/w)=B/A*100

 Where,
A is wt. of residue in gms.
B is wt. of sample in gms.

TOTAL ACID INSOLUBLE ASH

Acid insoluble ash determines the organic impurities present in the substance by
incinerating the substance at 600= or -25c.

Apparatus-
1. Silica/Platinum crucible.
2. A calibrated balance.
3. A dessicator.

Procedure-
1. Boil the ash obtained in the test for total ash with 25ml of 2 molar HCl for 5min
and filter on the filter paper.
2. Wash with hot water and ignite the filter paper in the crucible at 600+ or -25c till
all residues becomes white.
3. Cool the crucible and weigh it.
4. Caklculate the % of acid insoluble ash with help of weight of residue left out in
the crucible.

Acid insoluble ash (%w/w)=B*A100

Where,
A is wt. of substances under examination in gms.
B is wt. of residue of gms.

pH
The pH value conventionally represents the acidity or alkalinity of an aqueous solution.
It is also defined as the negative logarithm of the hydrogen ion conc.of solution.

pH= -log(H)

Procedure-
1. Use calibrated pH meter to measure the pH of aqueous solution.
2. Wash the electrode and temperature sensor with distilled water.
3. Remove the excess of water with the help of a filter paper.
4. Immense the pH electrode and temperature sensor in the test solution and read its
pH value at 25 + 2c.
5. After measurement wash the electrode 2-3 times with the distilled water.

SWELL VOLUME / SWELL POWER

It enables us to determine the swelling volume of the mucilage of isapgol in water.

Apparatus-
1. Calibrated balance.
2. 100ml graduated measuring cylinder.
3. Glass rod.

Procedure-
1. Weigh 1gm of sample in a 100ml graduated measuring cylinder and add 10ml
distilled water.
2. Shake gently for 1min and make up the volume upto 90ml with water.
3. Make up the volume to 100ml with water again shake gently with glass rod
approximate for 1min.
4. Allow it to stand for 3hrs.
5. Measure the volume of mucilage.
6. Carry out the test in triplicate and the average of 3 samples determine the swell
power of isapgol mucilage.

BULK DENSITY / TAPPED DENSITY

Bulk density of a powder is the value if the density in gm/ml as per powered or as
passively filled into a measuring vessel. Bulk density may also be defined as the ratio
of the sample weight taken and the sample volume occupied before tapping. The
tapped density is a limiting attained after tapping down. Usually in a device that lifts
and drops a volumetric measuring cylinder containing the powder a fixed distance.

Apparatus-
1. A calibrated balance.
2. Bulk density apparatus.
3. Dry 50ml graduated cylinder with stopper.

Procedure-
1. Fill the stopper dry granulated cylinder with sample under examination upto 50ml
mark.
2. Note the wt. of the sample and calculate the bulk density by the formula.

Bulk density (gm/ml) = w/v

Where,
w = wt. of the sample in gm.
v = vol. occupied by the sample before tapping

Procedure for tapped density-

1. Place the stopper and fix the cylinder on the bulk density apparatus.
2. Switch on the apparatus and start continuing the tapping for 50 taps.
3. Switch of the apparatus.
4. Note the volume occupied by the sample in the cylinder and calculate the tapped
density by the formula.
 Tapped density (gm/ml) = w/v
Where,
w = wt. of sample in gm.
vf = vol. occupied by the sample before tapping.

WATER SOLUBLE EXTRACTIVES

This test describes the procedure of determining water soluble extracts in sample or
material.

Apparatus-
1. Calibrated balance.
2. Pteridish / flat bottomed shallow dish.
3. Desscaiir with silica gel.
4. Water bath.
5. Electric oven.

Procedure-
1. Weight 1gm of powder in a 250ml stopper flask.
2. Add 100ml distilled water and keep for 24hrs shaking frequently during the first
6hrs and allow to stand for next 18hrs.
3. Filter and pipette out 25ml of the filterate in a pteridish.
4. Evaporate the filterate on water bath and then dry the dish at 105c.
5. Cool the dish in a dessicator.
6. Calculate the % of water soluble extract with the help of the residue left in the
pteridish after evaporation of filterate.

% water soluble extractives (% w/w) = A*100 / B*D

Where,
A = wt. of residue after evaporation of filterate.
B = sample wt.
C = volume of filterate taken for evaporation.

ASSAY
(a) Tannins (sample prepration)-
1. Weigh accurately 0.4gm of softovac powder in a 100ml volumetric flask.
2. Make up the vol. with water and stir for 15min and decant the supernatant.

Procedure-
1. Pipette out 50ml of the above solution in a 1000ml beaker and add 700ml of
distilled water.
2. Add 25ml of indigo sulphuric acid solution, stir the content with the help of a
magnetic stirrer.
3. Titrate with 0.01N potassium permagnet sol. Till a golden yellow end point
appears.
4. Each ml of 0.01N potassium permagnet sol. Is equipment to 0.0004157g of
tannins.
5. Run a blank test by titrating 25ml of indigo sulphuric acid in 750ml of water in a
1000ml beaker.

% tannins = ( burette reading blank) * N of potassium permagnet 0.0004157 * 2 *

100
0.1 * wt. of sample in gms.

(b) Calcium sennosoid ( reagents used)-

1. Ferric chloride solution (10.5%).
2. Magnesium acetate solution ( 0.5%).
3. Di-ethyl ether.
4. Conc. Hydrochloric acid.
5. Sodium bicarbonate.

Procedure-
1. Weight accurately 0.4gm of sample in a 100ml of volumetric flask.
2. Add 20ml of ferric chloride solution.
3. Add 0.1-0.5gm of sodium bicarbonate and 10ml of distilled water.
4. Shake gently and heat by dipping in a water bath for 20min.
5. Add 1.5ml of conc. HCl, shake well and heat again on water bath for further
20min till the precipitate or solution becomes clear.
6. Take out the the flask and cool.
7. Transfer the contents into a separating funnel and extract with 40ml of diethyl
ether.
8. Collect ether layer in the 100ml of volumetric flask and make up the volume with
ether.
9. Again extract twice with 25ml of diethyl ether.
10. Pipette out 25ml from it and transfer in the 100ml beaker and evaporate it on a
water bath at 50c to dryness.
11. Dissolve the residue in 25ml of magnesium acetate solution.
12. Pink colour is produced, shake well till the residue dissolves completely.
13. Filter and take the absorbance of the solution at 515nm.

% calcium sennosoid = SA*100 / SW

Where,
SA = sample absorbance
A = 240
SW = sample wt. in gms.
 MANUFACTURING PROCESS

RAW MATERIAL

SENT TO WAREHOSE

DISPENSING OF RAW MATERIAL

TRANSFER TO MANUFACTURING AREA

(as per batch manufacturing record)

SIFTING

MILLING

MIXING

DRYING

FINAL BLENDING

TRANSFER TO IPC

LOD AND MOISTURE CONTECT TESTING

(in process testing)

POWDER TRANSFERED TO POWDER FILLING MACHINE

FILL THE CONTAINOR

TO SCREW CAPING MACHINE TO CAP THE CONTAINOR

TO INDUCTION SEALING MACHINE TO SEAL THE CONTAINOR

LABEL THE CONTAINOR

PACK

FINALLY PACK IN CFB BOXES

LABEL FAKED GOOD TO DISTRIBUTION

CONCLUSION

I achieved a great deal of satisfaction and knowledge during my one month training at LUPIN
LTD. pharma industry.i gained a lot of insight into the industry by comparing the theoritical
aspects with practical aspects being followed. i got aquinted with industrial environment and with
industrial norms and practices being followed.

all my superiors and officers were very cooperative to lend the necessary support during my
traing period despite their hectic schedule.

i once again extend my heartfelt gratitute to each and every individual who directly or indirectly
helped me in completing my training successfully.