medicamen report

8/8/2019 Medicamen Report

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The manufacturing facility is divided into different block for Smooth

Functioning and to comply with the international norms: It has Beta-

Lactum, Non Beta- Lactum Block, ORS Block, Utilities Block and store

and quality control block.

1.3 Status of company :-

ISO 9001:2000 Certification :-

Medicamen recognizes quality to be the prime driver in pharmaceutical

industry and committed to adhere to international standards. The

company was granted ISO 9001:2000 with improved version valid till 12

June 2006.

WHO GMP :-

Medicamen has recognized the importance of WHO-GMP certification

for manufacturing medicines for export market and complied with

its requirement and obtained the certification on 19-11-1998 which

has been subsequently renewed after every two years. Beside WHO

GMP the company has faced a number of inspections from various

international agencies and by implementing the observation of these

agencies; medicamen has acquired distinction amongst the

companies of its size. To name, medicamens plant is approved in

Brazil, Uganda, Zimbabwe, Nigeria, Ghana, Yemen and Tanzania.

Membership :-

It has always been the policy of the company to have membership of

leading associations/organizations to have active interface with the

industry vis a vis government policies and the active legal and technical


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environment. Currently medicamen is the active member of the following

association/organizations

Confederation of Indian industry

Federation of Indian chambers of commerce and industry

Indian drug manufactures associations

Federation of Indian export organizations

CHEMEXIL

PHARMMAXIL

Indian trade promotion organization

Indian institute of management studies

Rajasthan pharmaceutical manufactures association

Bhiwadi manufactures association

Sh. B.K. Gupta, managing director is active member in various

specialized comities of FICCI, such as biotechnology committee,

taxation committee etc.

Export market :-

Medicamen had a mere turnover of Rs. 3 crores during 1996-97 but now

it is about to touch Rs. 50 crores with the constant growth in export

market. The company has grown from strength to strength and has the

distinction of getting IRYAT SHREE gold trophy from the ministry of

commerce, Govt. of India for 2 consecutive year of excellence in export

performance.

Joint Venture with Pharmadanica, Denmark :-

To strengthen its overseas operation Medicamen had entered into

strategic joint venture with Pharmadanica, Denmark in November 2002.

Our partners have the active marketing & logistic operation in 75


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countries throughout the world. They have participated both in equity

shares of the company and provide soft loan. The co-operation is going

on very well and we are working full-fledged in developing new products

and fixed dose packs for anti-malarial, anti-TB and HIV products for the

world market. We are targeting WHO Geneva approval in the near future

followed by approval in UK MHRA. European registration and then

finally US-FDA. The company is planning to be a major player in

generics in international market with the help of its partners.

Domestic Marketing :-The domestic ethical marketing was introduced during the year 2001 but

was at very nascent stage, but keeping in view the importance of ethical

business. The company has taken vigorous steps to penetrate into ethical

market. The company has appointed franchises throughout India and the

ethical market is slowly and steadily in the growth path.

Currently the company has a range of around 40 branded products in themarket and has established its network in the status of Delhi, Rajasthan,

Uttar Pradesh, Bihar, west Bengal, Orissa, Andhra Pradesh, Tamilnadu,

Kerala, Maharashtra, and J. & K., and is now in the process of covering

remaining territories.

Medicament also has a formalized under-license manufacturing

arrangement with its partner, Pharmadanica A/S Denmark to promote toethical market. The response from the market for the product range

packaging standard has been very encouraging.

Institutional Marketing :-

Institutional marketing has been one of the core business areas of the

company since inception. By virtue of its long list of WHO COPP


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approval, respectable turnover, market standing of large range of

products, the institutional business has been growing substantially every

year. The company has been participating in almost all national level

tenders and selected state level tenders.

Contract Manufacturing :-

For the better utilization of idle manufacturing facilities the company has

initiated contract manufacturing for come reputed pharmaceutical

companies in India. The company is currently contract manufacturing for

M/S Torrent Pharma Ltd and M/S Menarini Rounaq Pharma Ltd.

(affiliated to M/S A. Menarini,Italy). It was also contract manufacturing

some reputed brand of M/S Ranbaxy Laboratory Ltd. For more than six

years.

New Ventures :-

The company has an ambitious plan to establish a new formulation unit in

tax free zone to support its domestic business and the plant is likely to

come up in the financial year 2008-2009.


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2. FACTORY PREMISIS (SCHEDULE M)

2.1 Requirements of Factory Premises :-

(A) Location and surroundings : - The Factory shall be situated in a

place which shall not be adjacent to on open sewage, drain, public lavatory

or any factory which produces a disagreeable of obnoxious odor or fumes

or large quantities of soot, dust or smoke. The factory shall be located in

sanitary place, remote from filthy surroundings.

(B) Buildings : - The buildings used for the factory shall be

consummated so as to permit of production under hygienic conditions. The

walls of the room in which manufacturing operations are carried out shall,

up to a height of six feet from the floor, be smooth, water-proof and must be

capable of being kept clean. The flooring shall be smooth, even and

washable and shall be such as not to permit of retention or accumulation of

dust.

(C) Water Supply : - The water used in manufacturing shall be pure

and of drinkable quality, free from pathogenic micro-organisms.

(D) Disposal of waste : - Waste water and other residues from the

laboratory which might be prejudicial to the workers or to public health

shall be disposed of after suitable treatment to render them harmless.6


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(E) Health, clothing and sanitary requirement of the staff: - All

workers shall free from contagious or obnoxious disease. Their clothing

shall consist of a white or coloured uniform suitable to the nature of work

and the climate, and shall be clean.. Adequate facilities for personal

cleanliness, such as clean towels, soap and hand scrubbing brushes shall be

provided separately for each section.

(F) Medical services: - The manufacturing shall provide :

1. Adequate facilities for the first aid.

2. Medical inspection of the workers.

3. Facilities for vaccination and inoculation against the enteric or any

other epidemic group of diseases.

4. Adequate precautions for safeguarding the head of the workers.

(G) Working benches : - shall be provided for the carrying out

operations such as filling, labeling, packing etc.

(H) In factories where operations involving the use of containers, such

as bottles, vials, jars ampoules, are conducted, there shall be adequate

arrangements separated from the manufacturing operations for washing,

cleaning and drying such containers with suitable equipment for the

purpose . Sterilizing facilities where necessary should also be provided.

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2.2 Requirements of Plant and Equipments :-

(A) The following equipments are recommended for the manufacture

of syrups, elixirs and solutions :-

1. Mixing and storage tanks

2. Portable mixer

3. Filter press or other suitable filtering equipment, such as meta filter

or sparkled filter

4. Vacuum or gravity filter

5. Water still or Deionizer

An area of 30 square meters is recommended for the basis

installations.

(B) Equipment for the manufacture of pills and compressed tablets

including hypodermic tablets :-

For operations the tablet production department shall be divided into

three distinct and separate sections:

(a) Granulating section

(b)Tableting section

(c) Coating section

The following equipments are recommended in each of the three sections.

(a) Granulating section :-

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1. Disintegrator

2. Powder mixer

3. Mass mixer

4. Granulator 5. Ovens, thermostatically controlled

(b) Tableting section :-

1. Tablet machine, single punch or rotary

2. Pill machine

3. Punch and dies storage cabinet4. Tablet counter

(c) Coating section :-

1. Jacked kettle, steam, gas or electrically heated for preparing solution

2. Coating pan

3. Polishing pan

(d) The following equipments are recommended for filling of hard

gelatin Capsules :-

1. Mixing and blending equipment.

2. Capsule counters.

3.3 Manufacturing Area :-

1. Storage equipment for container

2. Water still

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3. Mixing and preparation tanks or other containers

4. Filtering equipment such as filter process or sintered glass funnel

5. Autoclave

6. Hot air sterilizer

7. Benches for filling and sealing

8. Filling and sealing unit

9. Bacteriological filters such as seitz filter candles or sintered glass

filters.

10. Filling and sealing unit

11. Inspection table

12.Leak testing equipment

13.Labeling and packing benches

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3. BETA - LACTUM BLOCK

3.1 Production Section :-

The term good manufacturing practices (GMP). I will understand, however

people having good theoretical knowledge of pharmaceutical principle and

adequate relevant experience in manufacturing generally compliance to

GMP.

In medicament biotech specially observed in appreciated the following

general aspect are

1. All equipment are utilized are of standard qualification.

The manufacturing process are regularly reviewed and revalidated.

2. Efficient clinic system and transfer from shift to shift use.

3. Equipments are arranged regularly.

There are four sections in production in beta - lactum block:

1. Tablet section2. Dry syrup section

3. Syrup section

3.1.1 Tablet Section :-

Tablet Production Area :-

1. Fabrication area2. Compression area

3. acking area

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Equipment available in fabrication area :-

Electronic balance

Mechanical sifter

Double cone blender

Machine available in compression area :-

Double side rotatory tablet compression machine

Machine available in packing area :-

Strip packing machine

Blister packing machine

Tablet counter machine

Mechanical sifter :-

In this moment is used to separate different fraction fraction at particular

size by using sieves of different no. (Siever no.

0,12,14,16,18,20,22,24,30,40,60,80,100,120.)

Multi mill granulator :-

In has eight curser in diameter, which crushes the lump, formed during

mixing. Its motion is oscillating type and out come is 22 kg per hour.

Screen no. used in multimill. (Screen no. 2mm,2.5mm, 3.0mm, 3.5mm.)

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Double cone blender :-

Figure 1: Double cone blender

Double cone blender is an electrically operated double cone shaped pan

rotating around its central axis. It is used for blending of screened granules

with lubricants and disintegrates.

Filling capacity of double cone blender = 250 kg,

Rotating speed = 10 rpm,

Motor Horse power = 5 H.P

3.1.2 Dry Syrup Section :-.

Dry syrup production area :-

1. Fabrication

2. Dry Syrup filling/sealing area

3. Labeling or final packing area

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Fabrication area available equipment :-

Shifter

Multimill granulator

Double cone blender

Dry syrup filling/ sealing area available machine :-

Dry syrup bottle cleaning machine

Dry syrup filling machine

Bottle sealing machine

Dry syrup packing area available machine :-

Semi automatic labeling machine.

Dry Syrup filling machine :-

Semi automatic dry syrup filling machine capacity = 60 bottle/min.

Dry syrup powder filling capacity =1gm 40 gm/bottle

3.1.3 Liquid Section :-

Liquid section is divided in different area :-

Fabrication Area

Formulation area

Bottle washing/ drying area

Liquid filling/sealing area14


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Packing area

Fabrication area available equipment :-

Shifter

Multi mill

Double cone blender

Formulation area available equipment :-

Heating SS tank

Manufacturing SS tank

Collided mill

Liquid transfer pump

Bottle washing/drying machine

Liquid filling/sealing area available machine :-

Eight head liquid filling machine

Cap holding/ cap sealing machine

Induction cap sealing machine

Packing area available machine :-

Semi automatic labeling machine

Heating SS tank :-

There tank that are using for storing of prepared liquid in constant temp is

capacity is 1000 liter.

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Manufacturing tank :-

There is a 1600 liter capacity syrup preparation tank.

Colloidal mill :-

Figure 3: Colloidal Mill

This is used for particle size reduction.

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4. NON - BETA - LACTUM BLOCK

Non-beta lactum block are two type of dosage form are manufacture.

Solid dosage form Liquid dosage form

Tablet Capsule Dry Syrup Suspension Syrup

4.1 Production of Solid Dosage Form :-

4.1.1 Tablet Section :-

Fabrication area

Compression area

Coating area

Packing area

Tablet compression area available machine :-

Onside rotatory machine 16 station

Double side rotatory machine 20,35,45 station

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Tablet coating area available equipment :-

Coating Pan

Solution manufacturing tank

Polishing Pan

Tablet packing area :-

Blister packing machine

Strip packaging machine

Fabrication Area Machine :-

Fluidized Bed Dryer (FBD) :-

This dryer provides more efficient drying than hot air oven it consist of

two ports, one is movable port in which granules to be dried are placed and

covering part has a material holding cloth and a sanction above the cloth.

After the attaching both portions hot and pressurizes air up lifts the granules

and dried efficiently. The sanction take out the humid airs which by passing

through heating coils re circulated.

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Figure 4: Fluidized Bed Dryer

RMG (Rapid Mass Granulator) :-

This mixer provides more efficient granule than planetary mixer.

Capacity the mixing material : 250 kg.

Rotating speed : 1428-2856 rpm.

Rotating speed in granulator : 50-60 rpm.

Motor power : 50 H.P. in mixer motor.

Tablet Compression Machine (number of machine 4):-

Tablets are made by compressing a formulation containing a drug or drug

with excipient on stamping machine called presses.

1. One side rotatory machine

2. Double side rotatory machine

Table 3: Comparison of Machines.

One side double side

rotatory machine rotator Machine

No. of station 16 20,35,45

Type of tolling 1 2

Max.operating 10 tones 6.5 tones

Pressure.

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Die size 8mm-12.5 mm 8m-12.5 mm

Coating pan :-The standard coating pan system consist of a circular matter pan mounted

some what angularity on a stand. There are five coating pan in this block

consisting a Aquarius shaped steel body that is used for sugar and film

coating, enteric coating. It consisting of a air pipe through which hot air

comes for drying for coating material filling capacity of each pan is 12kg, 40

kg, 60kg, for film coating 25 kg for sugar coating. This pan rotates on three

speeds in a slightly titled position.

Filling capacity :-

1. Small pan 12kg

2. Medium pan 40kg

3. Large pan 60kg

Figure 5: Coating Pan

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Type of coating :-

1. Sugar coating

2. Filling coating

3. Enteric coating

Polishing Pan :-

It is cylindrically shaped pan having an inner lining of wax and slightly

rough cloth and is used for polishing of coating material. It rotates in a

slightly inclined position at a speed 20rpm. Its filing capacity is 20 kg.

Process Adopted for Tableting :-

Tablet manufacturing process involves following steps:-

1. Preparation of granules for compression , it include

(a) weighing the ingredients

(b) mixing the powdered ingredients and excipients

(c) Converting the mixed ingredients into granules.2. Compression of granule into tablet

3. Coating of tablets

Preparation of Granules :-

(a) Weighing of the ingredients :-

The appropriate quantities of raw material are weighed using a balance of high quality.

(b) Mixing of the powdered ingredients and excipients :-

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Appropriate quantities of raw material mixed in a mass mixer in accordance

with GMP for blending of free flowing material with components of uniform

size and density.

(c) Converting the mixed ingredient into granules :-Granulating agent isadded in a mixed material; generally starch past is added to form a raw

material appropriate for granulation. Two method are used for granulation

1. Wet granulation: Dumped mass formed by mixing of drug material with

liquid placed in material for making granules which than dried in tray dryer

or fluidized bed dryer. Their dried granules are than screened by shifter.

2. Dry granulation: For dry granulation evaporating solutions are usedmixing of raw material is than placed into the roll compactor, through which

we get slug which than crushed and screened by shifter.

Compression of granules into tablet :-

Granules obtained from shifter are blended with lubricants and disintegration

agent in double cone blender. This blended material transferred into the

hopped of the tablet compression machine, which passes into dies through

bed shoe where this granule are compressed between upper and lower

punches and then collected in a double line drum.

4.2 Production of Liquid Section :- Liquid section is divided in different area

Bottle washing area / drying area

Fabrication area ( formulation chamber)

Liquid filling / sealing area

Labeling /packing area

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Formulation area available equipment :-

Heating S.S. tank

Mixing S.S. tank

Manufacturing S.S. tank

Liquid transfer pump

Colloidal mill

Filling area available machine :-

Liquid four head filling machine

Baby liquid filling machine

Sealing machine

Packaging area :- Automatic labeling machine

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5. INPROCESS QUALITY CONTROL TEST

5.1 Tablet :-

(1) Hardness (Limit N.M.T 1.0%):-

Tablets require a certain amount of strength, or hardness to withstand

mechanical shocks of handling in manufacturer, packaging and shipping. In

addition, tablets should be able to withstand reasonable abuse when in the

hands of consumer.

The following devices are commonly used by analyst to find out the

hardness of tablet.

Monsanto Hardness Tester:-

The

Monsanto chemical company limited had designed spring, pressure device to

test the hardness a tablet. It has a graduated scale which gives the reading in

Kg/sq Cm

Pfizer Tablet Hardness Tester:-It is bases on the principle of ordinary pliers. Pfizer tablet hardness tester is

a pliers fitted with a pressure dial.

(2) Friability (Limit NMT 1.0%):-24


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The crushing strength test may not be the best measure of potential tablet

behavior during handling packaging.

Figure 9: Friability Apparatus

(3) Weight Variation:-

A tablet must contain a proper amount of drug, for testing weight

variation a sample of 20 tablets. Taken hourly and random weighted on

electronic and physical balance. The tablet must having acceptable

average weight.

Table 9: Limits for weight Variation as per IP85

AVERAGE WEIGHT

OF TABLET

PERCENT

AGE

DEVIATI

ON1. 80 Mg or less 10%2. More than 80 Mg and

less than 250 Mg

7.5%

3. 250 Mg or more 5%

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(4) Thickness and diameter of tablet:-

Instrument Use - Vernier caliper scale

(5) Disintegration time:-

This is time in which breakdown of tablet in GIT occurs. To test D.T.

there is disintegration test apparatus is used that is stated as per

pharmacopoeia. A starch past is employed as disintegration agent which

may standards for D.T.

D.T. of various type tablets:-

D.T. for uncoated tablet = 15 minute

D.T. for coated tablet:-

Film coated = 30 minute

Other coated = 60 minute

D.T. for enteric coated tablet:-

No sign of disintegration in 0.1 N HCL for 2 hour and disintegrate in

phosphate buffer pH 6.8 in 1 hour.

D.T. for soluble tablet = 3minute

D.T. for effervescent tablet = 5 minute

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Figure 10: Disintegration Apparatus

(6) Leakage test:-

For this purpose leaker test apparatus is used

Strip pack -Maintain Vacuum at 250 mm for 30 sec.

Blister pack -Maintain Vacuum at 180 mm for 30 sec.

(7) Checked the common defect of tablet:-

Capping & lamination

Picking & sticking

Chipping

5.2 Dry Syrup :- Test performed for dry syrup:-

Weight variation

Average weight

Sealing checking test

Leaker test

5.3 Liquid :- Test performed for dry syrup:-

Average weight27


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Uniformity of weight/volume

Inspection for foreign particles

Bottle leakage test

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6. QUALITY CONTROL LABORATORY

The maintain the quality of product in last or finished product called quality

control (Q.C.), ensures product stability keeping the compliance to GMP

going and assures that the product will retain all their claims till they are

consumed.

Q.C department is divide in following area:-

Instrumental lab

Chemical lab

Microbiology lab

Instrumental lab:-

Equipment available in Instrument Lab:-

Polari meter

Digital P H meter

Dissolution rate apparatus [6 basket is used at a time]

Inflorescence light apparatus

Karl fisher universal titrator

Flame photometry

U.V/visible spectrometer

Refractrometer

Karl fisher titrator

HPLC-2 {one is manual & one is automatic}

Fourier transform infrared spectrophotometer

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Chemical lab:-

Disintegration test apparatus

Friability apparatus

Action shacking machine

Centrifuge machine

Magnetic stirrer

Melting point apparatus

Sonicator

Bulk density apparatus

Single distillation still [ for HPLC water]

Microbiological lab:-

Equipment available

Auto clave

Refrigerator

B.O.D

Laminar air flow

Incubator

Cubic colony counter

Antibiotic zone reader

Membrane filter assembly

Kimark stand

Vacuum pump

Hot air oven

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Fumicator

Temperature tester

Procedure of quality control:-

1. Raw material analysis:-

After receiving raw material in store division. Q.C. dept is called for

sampling for testing its quality & purity as per pharmacopoeia. If the raw

material stood in its Q.C. passes the raw material for production for

inspections two samples from each of the tablet, capsule, liquid section are

selected, one is meant for testing and another is for storage.

2. In process control:-

There is a real and significant difference between a finished product and the

quality assurance of the manufacturing process.

For control sample size usually taken as-

1. 100 tablets [ 10 packets ]

2. 10 bottles of liquid

3. 10 bottle of powder

4. 100 capsule [ 10 packet]

There are many equipment used in each section for testing during the in

process are-

1. Electronic balance2. Disintegration test apparatus

3. Friability test apparatus

4. Hardness tester

5. Vernier calipers

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6. Measuring cylinders

Description:- Describe physical property of sample as color, odor, physical

state.

Solubility:- Maximum amount of solute dissolve in minimum quantity of solvent.

Identification:- Conformation about sample.

Color & color of solution:- Substances give specific color in presence of

reagent specified in I.P.

Limit test:- Quantitative and semi qualitative determination of elements

present in sample.

Loss on drying:- Rare observed water or water of hydration is determined by

specified condition.

Sulphated ash:- Sample dissolves in sulphuric acid and put in to MUFFLE

FURNACE. Determined residue as sulphated ash.

Titration:- Titrand and titrent are used in titration in standardization of

solution.

Assay:- To determine actual quantity of active ingredient present in sample.

Disintegration:- A generally accepted maxim is that for a drug to be readily

available to the body, it must be in solution. For most tablets, the first most

important step towards solution is breakdown of the tablet in to smaller

particles or granules, a process knowledge known as disintegration.

Dissolution:- The original rationale for using tablet disintegration test wasthe fact that as the tablet breaks down small particles it offers a greater

surface area to the dissolving media and therefore must be related to the

availability of the drug to the body.

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Test for water:- This test is done to determined quantity of moisture/water

present in sample. Determined by KARL FISHER titrametric method.

Stability data generation and handling:-HPLC- In the past few years, stability testing has been revolutionized by too

highly technologic advancement -high pressure liquid chromatography

(HPLC) methodology, and the computer for stability data acquisition,

storage, analysis and reporting.

Method used for checking the quality:-

1. Electrical method:-

It is a titrametric method that can be used for the precise analysis of active

ingredients.

2. Solvent extraction method:-

It is possible to extract acidic, neutral, of basic compounds from organic

solvent on the basis of partial behaviors of their ionized and unionized

species.

3. Spectrophotometric Method:-

This methods is widely used in pharmaceuticals for this material is separated

by the solvent and than its put in the spectrophotometer and observations

taken

4. chromatographic method:- Now days TLC is replaced by HPLC and rarely used in Medicamen Biotech

Ltd.

Quality assurance control:-33


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The concept of quality control refers to the process of starting to produce a

perfect product by a series of measures requiring an organized effort at

every stage in production.

Quality control ensures product stability keeping the compliance to GMPgoing and assures that the product will retain all there claims till they are

consumed.

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7. BIBLIOGRAPHY

1. Indian Pharmacopoeia, Government of India, Ministy of Health and

Family Welfare, The controller of publication,1996 New Delhi.

2. Lachman Leon, Libberman A Herbert, The Theory and practice of

industrial Pharmacy,1991, Varghese Publishing House, Bombay.

3. Remingtons- The science and practice of pharmacy, international student

edition, 20 th ed. 2000 Philadelphia College of Pharmacy and Science,

Philadelphia.

4. Ansels Pharmaceutical Dosage forms and Drug Delivery Systems 8th

ed.B.I. Publications Pvt. Ltd. Lippincott Williams and willkins, Philadelphia.

5. Bentleys textbook of Pharmaceutics 8 th ed. Published by all India

Traveler Book Seller, Delhi.

6. Pharmaceutics The science of Dosage from Design International

Student edition, edited by M.E Aulton, London.

7. Kohli D.P.S and Shah D.H Drug formulations Manual Eastern

Publishers, New Delhi.

8. Sharma P.P How to Practice GMPS , Vandana Publications Pvt. Ltd.

New Delhi.

9. United State Pharmacopoeia, 23 rd edition.

medicamen report

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