TRIP

TO
MEDICAMEN BIOTECH
Ltd. (BHIWADI)

Amit Anand
VII Semester
04219611
Contents:
1. Introduction
2. Receiving the material
3. Storage
4. Dispensing
5. General manufacturing process
6. Manufacturing of Tablets
7. Capsules
8. Liquids
9. Quality Assurance and Quality Control
10.Utility
11.Conclusion

MEDICAMEN BIOTECH LIMITED ( BIWADI ) was established on 22nd December

1993 while it entered the stock –exchange in 1995 .Second plant at HARIDWAR was
established in 2007 .We visited the BHIWADI PLANT on
BHIWADI PLANT
It is spread over an area of 2, 10,100 sq.ft. having ultra modern production facilities
incorporating latest state of art technology with combination of technically qualified and hard
working force. It is divided into 5 blocks
 Ware House ,QA and QC
 Non Beta –Lactum :Tablets ,Capsules /P.F.S
 ORS and Liquids
 Beta-Lactum
 Utility
PRODUCTION CAPACITY

NON BETA-LACTUM
1. Tablets ____________________ 8 Million per Day.
2. Capsules ___________________1 Million per Day.
3. Oral Liquid _________________4600 Liters per Day.
4. Dry Syrup __________________6000 K.G. per Day.
5. ORS ________________________1, 80,000 Sachets per Day.
BETA-LACTUM
1. Tablets ____________________1 Million per Day.
2. Capsules ___________________1 Million per Day.
3. Liquid _____________________1300 Liters per Day.
4. Dry Syrup __________________50,000 Bottles per Day
HARIDWAR PLANT

NON –BETALACTUM preparation like tablets, capsules, oral liquids and ointments and
creams are produced.

PRODUCTION CAPACITY
1. Tablets ___________________4 Million per Day.
2. Capsules __________________0.5 Million Per Day.
3. Oral Liquid _______________ 4000 Liters per Day.
4. Ointments & Creams_________200 Kg. per Day.

RECEIVING OF RAW MATERIALS:

Raw materials are received at Receiving Bay whose entrance is on front side of block.

Before coming at receiving bay security at entrance gate of plant takes the challan and inform
and inform store in charge .On receipt ,visual examination of labels are made, damage to
containers, spoilage are examined .Particulars of challan are tallied with labels on container of
label .Then Goods –in Inspection Report is prepared .
Goods –in Inspection Report

Date of receipt………….
Delivery challan/invoice No………….. Dated………

Name and Address of Supplier …………………………………………………….......................

Name of items mentioned in Delivery challan /invoice (D/C/Inv)

1)……………………………..

2)……………………………..

3)………………………………

A. Check the following

a) Whether total number of containers mentioned in challan Yes/No (State total No. tallies with the number of
containers received? Containers)

B.What is the break up Name of items No. of containers

Of items and No. of containers

C.Do the following particulars Name of item………………..Yes/No

On label of container and challan tally Name of manufacturer………Yes/No

Batch No. …………………Yes/No

Date of expiry …………… Yes/No

B. Inspect all the containers and record the observation

aware all the containers damaged Yes/No

b. If no (1) No of containers damaged ………………………………................

(2)Name of item along with batch No…………………………………

C. Extent of damage:

a) Is damage to outer covering only? Yes/No

If no, to what extent has container been damaged?.....................................

b) Has material been contaminated with dust, fibers, and pieces of packaging Yes/No

materials?

D. Put conspicuous identification mark on damaged containers

Signature

Name of the person who carried out inspection ……………………….

Date ……………………….. Signature with Date Store in-charge

SOPS for Handling Shortage /Damaged and Open raw materials

1. If raw material being received is open/damaged/shortage store in-charge should prepare
“Open Delivery Certificate “and get dully signed by transporter.
2. Should submit the same to Account /Purchase department
3. If raw material is open ,it should be covered and sealed with polythene bag .Spillage
should be collected in polythene bag and dispose of as “disposable material from
warehouse

STORAGE
 Starting material is then transferred to quarantine area and is labeled as “Under Test “.
 Request is made to In-charge Quality control for sampling .Quality control personnel, on
receipt of request draw sample from raw material so quarantined.
 On receipt of “approval “or “rejection “starting material should be transferred to are
marked for approved material or rejected material according to status of the material
Colour codes are also used
Green : approved
Yellow: under test
Red: rejected
 Labels indicating status of the material are attached by the person authoriosed by Quality
control department.
 Those materials that require special storage condition (controlled temperature and
humidity) are stored in special storage area provided for this purpose.
 All materials are stored in such a way that permit batch segregation and stock rotation by
a “first in –first expiry –first out “.
 Inventory of all starting materials should be maintained as per schedule U to the Drugs &
Cosmetics Rules.
 Raw materials in storage area are labeled with following particulars
i. Designated name and internal code if any
ii. Analytical reference number
iii. Manufacture’s name ,address and batch number
iv. Status of the content (quarantine, approved ,rejected)
v. Manufacturing date, expiry date and re-test date
DISPENSING
There is separate dispensing booth where ingredients are weighed and dispensed. It consists of
three filters:

 HEPA: 0.3 micrometer pore size

 INTERMEDIATE: 0.5 micrometer pore size
 PRE FILTERS: 0.10 micrometer pore size

It also consists of Magnehelic meter –Reading should be between 0.5-15 mm hg of water.

Magnehelic pressure gauze

Inside the dispensing area pressure is kept positive while outside is kept negative so that any
microorganism or dust is present is thrown outward.

 Material is issued against written demand (requisition) for each batch of product.
 Each dispensed material and its volume /weight should be checked by another person and
such check should be recorded.
 Only those materials which has been released by Quality control department and have
adequate shelf life should be used in manufacturing of drugs.
 Inventory of all starting materials should be maintained as per schedule U to the Drugs &
Cosmetics Rules.

GENERAL MANUFACTURING PROCEDURE

 PLANNING DEPARTMENT

PRODUCTION ORDER (PO) FORMULATION ORDER (FO)

Raw material /packing material are checked

Sent to QA

QA submit report to production

Report goes to dispensing unit

Checking for quantity of material

According to BPR Production unit gets the ingredient from dispensing unit

Materials are checked Fabrication quality checked once more

According to label

Formulation

SOP S

In process quality control viscosity, density, other parameters

After preparation sample sent to QA for quality control

Approval for packaging (production)

Filling starts and packaging is done

QA for finished good quality control

Approved

Packed in shippers

Transfer ticket

Storage Market
 OUTLINE OF MANUFACTURING

MANUFACTURING OF TABLETS
 Dispensing according to BPR ( batch production record )
 Raw material staging
 Granulation
 Blending
 Compression
 Coating
 Packaging

MIXING: We first mix the active drug with the excipients such as Diluents Binding agent,
disintegrants, lubricants, glidants and flow promoters in shifter with specified mesh size .The
above shifted materials are loaded in RMG.

GRANULATION:
It is pharmaceutical process that attempts to improve the flow of powdered material by
forming sphere like or regularly shaped aggregates called granules.

TYPES OF GRANULATION 

GENERAL PROCESS SPECIFIC METHODOLOGY

Wet granulation Wet massing

Fluid bed granulation
Spray drying
Pan granulation
Extrusion and palletizing

Dry granulation Roller compaction

Slugging

Other processes Humidification

Melt pelletization
The major reason for granulating the powdered starting material in the
manufacture of tablets and granules are to:

 To improve the flow properties so that, the mass uniformity of the dose.
 To prevent segregation of ingredients in the mixture.
 To improve the compression characteristics of the mixture.
 To reduce the environmental hazards for the working personnel due to dust formation
from toxic materials.
 To reduce the bulk volume of voluminous powders and make them more convenient for
storage and transport.
 To improve the appearance of the product.(4)
 The granules being heavier do not blow out of the die and do not clog the lower punch.

WET GRANULATION: The unique property of wet granulation process involve the wet
massing of powders, wet sizing or milling and drying.
 It forms granules by binding the powders together with adhesive (BINDER). Wet
granulation employs solution, suspension or slurry containing binder .Many times binders
are mixed with other ingredients and solvent is added later on in RMG (rapid mixing
granulator).
Instruments required for wet massing granulation
 RMG(rapid mixing granulator
 Fluid Bed Dryer
 Vibro Sifter
 Multimill
 Paste making kettle
Procedure (For wet massing)

STEP 1: Granulation
 The active ingredient and excipients are weighed and mixed and loaded in RMG and
mixed for about 20 minutes to insure inform distribution of drug.
 Next added water in interval of 1-2 minutes while slowly mixing in RMG.When all water
has been added mix at high speed for 4-5 minutes.
 Added extra water if needed.
 Switch on the chopper for 1 minute and unload the RMG in bowl of Fluid bed dryer.
 Note
i. Dial reading of agitator
ii. Dial reading of chopper
iii. Extra water added
iv. Time of granulation
 RAPID MIXING GRANULATOR

STEP 2: Wet screening

Wet screening converts the moist mass into coarse ,granular aggregates by passage through a
Hammer mill or oscillating granulator ,equipped with screens having large perporations .The
purpose is to further consolidate the granules ,increase particle contact and increase surface area
to facilitate drying .

STEP 3: Drying
A drying process is required in all the wet granulation procedures to remove the solvent that
was used in forming the aggregates and to reduce the moisture content to an optimum level of
concentration within the granules .Mostly it is carried in Fluid Bed Dryer:

Fluid Bed Dryer:

It works on the principle that when hot air is passed at a high pressure through a perforated
bottom of the container containing the granules to be dried ,the granules are lifted from bottom
and suspended in stream of air .This condition is called “fluidized state ./The hot air is
surrounding each granule to completely dry them.

Construction: as shown in the diagram.

Working: The granule to be dried I placed in a detachable bowl .The bowl is pushed in the
dryer .Fresh is allowed to pass through pre filters, subsequently gets heated by passing through
heat exchanger. The hot air is blown from bottom of bowl .Simultaneously fan is allowed to
rotate .The air velocity is gradually increased till granules are suspended in air stream.

Uses: It is popularly used in drying of granules .It can be used for mixing, granulation and
drying.
 FLUID BED DRYER
Note:

(1) Initial temperature of air (2) Inlet temperature (3) Outlet temperature

(4) LOD (loss on drying) (5) Temperature for drying.

Step 4: Dry screening and milling

After drying sift the material through a specified mesh (mentioned in BPR) and collect in a
polythene bag. Lumps are broken multimill and then subjected to shifting.

Sifting :It is process of separation of mixture of various sizes of particles into two or more
portions by means of screening surface.

VIBRO SIFTER

Size reduction: It is a process of reducing large solid unit masses into small unit masses,
coarse particles or fine particles .Helps in content uniformity.

Multimill: To manage the size reduction of the material, the pharmaceutical Multimill uses all
the principles of variable forces such as grinding, compression, impact and shearing in an
effective manner in its functions

Multimill
Step 5: Sifting of lubricants through a particular mesh in vibro sifter (such as #
36)
1) A. MMC B. Sodium starch glycolate c. Colloidal anhydrous silica
2) Magnesium stearate and Talc through # 60

Step 6:Blending –It means to mix smoothly and inseparably together .Screened and milled
powder is placed in octagonal or double cone blender and blended with the lubricant for
specified time .
 Double Cone Blender

 Mechanism of mixing by double cone and octagonal blender is Tumbling action.

Octagonal blender

Step 6: Compression

Powder compression:
Powder compression it is defined as the reduction in volume of a powder owing to the
application of forces. Because of the increased proximity of particle surfaces accomplished
during compression, bonds are formed between particles which provide coherence to the powder
i.e. compact is formed.

Effect of Compression:
Effect of Compression When external mechanical forces applied to a powder mass there is
reduction in bulk volume as follows Repacking Particles deformation Elastic deformation-e.g.
acetyl salicylic acid, MCC Plastic deformation-at yield point of elastic. Brittle fracture – e.g.
sucrose Micro quashing-irrespective of larger particles, smaller particles may deform plastically.

Tablet production:
Tablet production Powders intended for compression into tablets must possess two essential
properties Powder fluidity The material can be transported through the hopper into the die To
produce tablets of a consistent weight Powder flow can be improved mechanically by the use of
vibrators, incorporate the glidant Powder compressibility The property of forming a stable, intact
compact mass when pressure is applied

Compression process:
 Filling
 By gravitational flow of powder from hopper via the die table into die.
 The die is closed at its lower end by the lower punch.
 Compression
 The upper punch descends and enters the die and the powder is compressed until a
tablet is formed.
 During the compression phase, the lower punch can be stationary or can move
upwards in the die.
 After maximum applied force is reached, the upper punch leaves the powder i.e.
the decompressed phase.
 Ejection
 During this phase, the lower punch rises until its tip reaches the level of the top of
the die.
 The tablet is subsequently removed from the die and die table by a pushing
device.

Tablet compression machine:

 Hopper for holding and feeding granulation to be compressed
 Dies that define the size and shape of the tablet
 Punches for compressing the granulation within the dies
 Cam tracks for guiding the movement of the punches
 Feeding mechanisms for moving granulation from the hopper into the dies
 TABLETINGMACHINE

Step 7: Tablet coating – It is done to mask the taste ,odor or the colour of the drug .It also
provides physical and chemical protection to the drug .Further release can also
controlled.Colours used are approved by Drug$ Cosmetic Act.

TABLET COATING MACHINE

Step 8: Packaging

It is of two types Blister packaging and Strip packaging

BLISTER PACKAGING MASCHINE.

STRIP PACKAGING MACHINE

CAPSULES: These are solid dosage form in which medicines are enclosed in a small shell of
gelatin .Shell is of two types

Hard gelatin: formed from animal skin by acid hydrolysis.

Soft gelatin: formed of bovine bones by alkaline hydrolysis.

Excipients used are colouring agent, diluents, preservatives and antioxidants .Soft gelatin also
contains Plasticizer such as glycerin and sorbitol.
LIQUIDS (syrups)
It involves following unit operations

 Dispensing according to BPR ( batch production record )

 Raw material staging
 Dissolving all materials except active in water
 Filter through filter press
 Mixing in main tank
 Addition of colour with stirring
 Size reduction in Colloidal mill
 Addition of flavouring agent
 Passing the liquid in storage tank
 Finally adding the Actives with stirring
 Preparation is ready for packaging in Pouch or bottle

Colloidal mill:
It works on the principle that when material is passed through two discs in which one is
rotating and other is static ,the particles are broken down into small particles due to shear
.

QUALITY

QUALITY ASSSURANCE: It establishes systems for ensuring quality of the products .QA
serves as the primary contact with the regulatory bodies and is the final authority for product
acceptance or rejection.
Medicamen follows Good Manufacturing Practices (CGMP) and current Good Laboratory
Practices (cGLP).Production and all other operation are clearly specified in a written form and
Standard Operating Procedures (SOPS) are adopted .All necessary controls on starting materials
including vendor audit ,intermediate products, and bulk products and other in quality controls,
calibrations and validations are carried out regularly .

QUALITY CONTROL : It most commonly function to test and measure material and
product QC is responsible for day to day control of quality within the company .It is staffed with
scientists and technicians for sampling and analytical testing of incoming raw materials and
inspection of packaging components including labeling .Finally it conduct tests on finished
products.

INSTRUMENTS USED IN QC:

HPLC: High-performance liquid chromatography (or high-pressure liquid

chromatography,HPLC) is a chromatographic technique that can separate a mixture of
compounds and is used in biochemistry and analytical chemistry to identify, quantify and purify
the individual components of the mixture.
 OUTLINE OF HPLC

PH meter: It is used to measure pH of given formulation. PH METER

 DIAGRAMATIC VIEW OF PH METER

DISSOLUTION APPARATUS: It is used to determine dissolution of tablets.

SECTROPHOTOMETERY: Spectrophotometry involves the use of a spectrophotometer.

A spectrophotometer is a photometer (a device for measuring light intensity) that can measure
intensity as a function of the light source wavelength. Important features of spectrophotometers
are spectral bandwidth and linear range of absorption measurement.
U.V CHAMBER
DISINTERATION TESTING : For a drug to be absorbed from a solid dosage form after
oral administration, it must first be in solution, and the first important step toward this condition
is usually the break-up of the tablet; a process known as disintegration.. Tablet Disintegration
Apparatus is used to measure the time taken by the tablet or a capsule to disintegrate.
Utilities Area – Control Room and Floor Operations

General Objectives:

 Operate & Monitor site (including satellite location) building and utility systems to:
 Supply critical services to the site including Steam, Electricity, Chilled Water, Potable
Water, and Nitrogen
 Maintain Building conditions within required parameters for ongoing scientific endeavors
 Respond to and restore conditions/services upon recovery from unplanned/abnormal
events such as power outages or system failure.

CONCLUSION:
The trip to the industry was a chance to see the manufacturing process at industrial level .It was
really exciting to see the changes from laboratory level. It provided insight to the manufacturing
equipments and processes with the help of which we can better understand the text part of the
same.