Undergraduate Industrial Training

FDC INDIA (Research & Development) Training period:-14.02.2011 31.03.2011 Report for the term 14.02.2011 -19.02.2011

Ms. Gunjan S. Patel Roll No.:- 41

FDC
FDC (Foods, Drugs & Chemicals) formerly known as Fair Deal Corporation, has been in the pharmaceutical business for more than seven decades now.

History Of FDC
1936:-With a modest beginning in 1936 marketing vitamins and a range of prescription formulations - FDC set up its first formulations manufacturing facility in 1949. 1963:-Subsequently, in 1963, FDC pioneered the manufacture of specialized ophthalmic formulations in India.FDC was the first organization to introduce the BFS (BLOW-FILL-SEAL) technology for ophthalmics in South East Asia. 1972:-In 1972, FDC initiated the concept of Oral Rehydration Salts (ORS). Today its pioneer brand 'Electral', stands apart with a special identity- an impressive achievement in a fiercely competitive market. 1984:-FDC's API plant at Roha (Maharashtra) was among the first few API facilities in India to get US-FDA approval in 1984. Since then, FDC has to its credit a number of new molecules, introduced for the first time in the nation.

Achievements
} } 2008:- * Received US FDA nod for two ophthalmic products * USFDA approval received for Waluj without any observations (No 483's) } 2002:- * First UK-MHRA approval for oral solids facility at Goa } 1999:- * Formed a JV in UK

} }

2007:- * MHRA approval received for Goa} I * MHRA reapproval received for Waluj }

1998:- * UK-MHRA approval for ophthalmic facility at Waluj

2006:- * Forbes rates FDC as the "BEST UNDER A BILLION COMPANIES" }

1996:- * Public issue of 26, 28, 200 equity shares of Rs. 10 each at a premium of Rs. 90 each * FDC awarded 'Export House' status * FDC established a specialized & dedicated field force to promote its ophthalmic specialties

} }

2005:- * First US-FDA approval for ophthalmic facility at Waluj * Filed 2 ANDAs for ophthalmic dosage forms in the U.S.

} }

2004:- * JV in the UK converted to a Wholly Owned Subsidiary * Established JV in South Africa

Achievements
} 1994:- * FDC became the first company in } India to introduce ophthalmics in blow-fillseal packs, which optimize sterility and are highly user friendly 1992:- * National Award from the Council of Scientific Research and Industry for Indigenous R&D of Flurbiprofen and Timolol 1991:- * Biotechnology research center set up at Waluj. } 1984:- * Foods division set up for manufacture of specialized infant foods at Roha 1977:- * Active Pharmaceutical Ingredient (API) plant commissioned at Roha, Maharashtra 1974:- * FairDeal's R&D facilities obtain recognition from the Govt. of India 1972:- * Electral introduced by FairDeal a result of pioneering work in rehydration therapy 1963:- * FairDeal introduced Vanmycetin Eye Drops starting point for its ophthalmic and ENT range 1949:- * Formulation plant established in Jogeshwari, Mumbai 1936:- * Mr. Anand Chandavarkar set up FairDeal Corporation (FDC) to import drugs, infant foods and surgical appliances for distribution in India }

} }

* Started production of Timolol Maleate } (API). 1989:- * Began commercial production of Flurbiprofen 1987:- * Commissioned a formulation Plant at Waluj, Aurangabad (Maharashtra) } 1986:- * FairDeal Corporation (Pvt.) Ltd. was renamed FDC Pvt. Ltd. and thereafter FDC Limited 1985:- * First US FDA approval of API plant at Roha

Locations Of Plants
Besides being successful in marketing its wide range of products in the domestic market, FDC also exports many of these products to Canada, USA, UK, Europe, Japan and several countries in the Middle East, Asia and Africa. The company has the most modern manufacturing facilities at Mumbai, Waluj (UK-MHRA approved) , Roha(US-FDA and WHO-GMP certified ) , Sinnar(a technologically advanced and a high capacity plant for ORS-Oral Rehydration Salts) and Goa (UK-MHRA approved) .

Products Manufactured
Anti Fungal/Dermatological Anti-Anaemic Anti-Diabetic AntiDiarrhoeals/Intetinals/ORS Anti-Haemorrhagics Anti-Oxidants Anti-Spasmodics Antibiotics/Antibacterials Antiemetics/Antinauseatic Antivirals Antimalarials Antiulcerants Calcium Supplements Cardio-Vascular Central Nervous System ENT and Related Genito Urinary Syatem & Sex Hormones Laxatives Musculo-Skeletal System Opthalmics Orthopaedics Otologicals Pre-Probiotics Respiratory & Antiallergic Stomatologicals Vitamins &Nutraceuticals

Organogram of Research & Development Department

Research & Development Department (Analytical)

ARDLI

ARDLII

ARDLIII

Method Develo pment (Semiregulat ory & Domes tic Market )

Domest ic

Validati on & Technol ogy Transfer

Semiregulat ory Querie s& Validat ion

Regula tory Market

Stabilit y Studie s

ANDA

Stabilit y

Third Party Sampl e Analysi s or Loan Licens e

Sampl e Analysi s from Locatio n

Brief Introduction
I have been placed under ARDL-I Department. Mr. Rajesh N. Mali is the Manager of this department. In this department the various sub-units are; Method Development (Semi-Regulatory & Domestic Market) Domestic Department Validation & Technology Transfer Semi-Regulatory queries & Validation.

I was in the Method Development Department whose Group Leader is Dr. Gunesh Gundi. The Group Leader of Domestic Department is Mr. Pravin Botre. The Group Leader of Validation & Technology Transfer id Mr. Sarvesh Bane. The Group Leader of Semi-Regulatory queries & Validation is Mr. Avadhoot Supal.

In the Method Development Department, the various analytical methods for specific durgs which are manufactured are developed. These include Assays, Dissolution ,Related Substance, pH, Identification tests, etc.

14th February, 2011.

On 14.02.2011, I met the HR. He took me to the ARDL-I (Analytical Research & Development Laboratory-I) and there I met Mr. Rajesh Mali who is the manager of the department. Mr. Rajesh Mali introduced me to the whole department employees and further from there Dr. Gunesh Gundi guided me. Dr. Gunesh Gundi gave me a detailed information on how their group worked on the development of the methods and all other units in that department. Thereafter I was given SOPs (Standard Operating Procedure) of all the instruments which were used in the laboratory and I read all of them the whole day.

14th February, 2011 contd

List of SOPs r : Use of Standard Units & Abbreviations. Stability Test Chamber. Operation & Cleaning of Lab Refrigerator. Magnetic Stirrer. pH Meter. Milli-Q water purification system. Dissolution Tester. HPLC. Analytical Balance. Gas Chromatography. Ultrasonic Bath.

Chromatography

15th February, 2011

On 15th February, I was with Mr. Sachin. He gave me a brief introduction of the working of the HPLC instrument. We performed and experiment to develop assay ethod for the preservatives used in Azapentacene Eye Drops. Preservatives : Methyl Paraben Propyl Paraben Thiomersal

HPLC
Pri cipl of HPLC:High Perforamnce Liquid Chromatography is a chromatographic technique that can separate a mixture of compounds is used in biochemistry and analytical chemistry to identify, quantify and purify the individual components of the mixture. Diff r c b tw Norm l Ph s R v rs Ph s Chrom to r phy:Normal Phase Chromatography separates analytes based on polarity, it has a polar stationary phase and a non-polar mobile phase. Reverse Phase Chromatography separates analytes using a non-polar stationary phase and a moderately polar mobile phase.

15th February, 2011 cont

Different Parts of HPLC: Mobile Phase / Solvent Reservoir Degasser Solvent Delivery System (Pump) Injector Precolumn Column Temperature Control Detectors Recorder (Data Collection)

HPLC Basic Instrumentation

Solvent Delivery Injector Column Separation Mobile phase Pump Sample Injection

Detector

Data Processor

r ,

11

On 1 t r r I p rform d TLC. W w r id ntif ing Ros Oil from MOISAL E Drops. TLC Principl : T Principl is C rom togr p s d on ADSORPTION ffinit tow rds t

T compon nt wit mor st tion r p s tr v ls slow r.

T compon nt wit l ss r ffinit tow rds t st tion r p s tr v ls f st r.

St tio
NAME Silica gel H Silica gel G Silica gel GF Alumina Al203 G Cellulose powder Cellulose powder Kieselguhr G Polyamide powder Fullers earth Magnesium Silicate

ry ph s
COMPOSITION Silica gel without binder Silica gel + CaSO4 Silica gel + Binder + fluorescent indicator Al203 Without Binder Al203 + Binder Cellulose Without Binder Cellulose With Binder Diatomaceous earth + binder Polyamide Hydrous magnesium alumina magnesol

Mobile phase
1) Nature of the substance to be separated i e weather it is polar or non-polar. non2) Mode of Chromatography. 3) Nature of Stationary phase. 4) Mode Separation i e Analytical or Preparative. Examples: 1) Petroliam ether 3) Acetone 5) Ethyl acetate 7) Alcohols 9) Chloroform 2) Cyclohexane 4) Toluene 6) Benzene 8) Water 10) Pyridine

Application of sample
The concentration of the sample shoul be 2--5l of a 1% solution. 2--5l

Sample is spotte usi g a capillary tube or micropipette.

Spots ca be place at ra

om process .

Spots shoul be kept atleast 2cm above the base of the plate.

Spotti g area shoul

ot be immerse i the Mobile phase.

Go for evelopme t.

Development tank
The development tank should be lined Inside with filter paper moistened with mobile phase to saturate the atmosphere & also prevent the EDGE EFFECT .

Detecting agents
Detecting agents are two types. they are, (A)Non(A)Non-Specific method
1) Iodine chamber method. 2) Sulphuric acid spray method. 3) UV chamber for fluorescent compounds. 4) Using fluorescent stationary phase.
(B)

Specific method
1) 2) 3) 4) 5) Ferric chloride. Ninhydrine in acetone. Dregendroff reagent. 3,5 Dinitro benzoic acid. 2,4 - Dinitro phenyl hydrazine.

detection
The Rf value is calculated for identification "Rf value is the ratio of distance travelled by The solute to the distance travelled by the solvent front front Distance travelled by solute Rf = Distance travelled by solvent front

Comparison of tlc & hplc

17th, 18th &19th February, 2011

On all these 3 days I worked alongwith Mr. Sachin to develop the Assay method for Nizi tablet. Label Claim: Each uncoated tablet contains: Nimesulide-100mg Tizanidine HCl equivalent to Tizanidine-20mg.

Nimesulide

Nimesulide
} Nimesulide is a relatively COX-2 selective, non-steroidal antiinflammatory drug (NSAID) with analgesic and antipyretic properties. Its approved indications are the treatment of acute pain, the symptomatic treatment of osteoarthritis and primary dysmenorrhoea in adolescents and adults above 12 years old. Due to concerns about the risk of hepatotoxicity, Nimesulide has been withdrawn from market in many countries } Central Drugs Standard Control Organization of India bans Nimesulide } Several reports have been made of adverse drug reactions in India . On Feb 12, 2011, Express India reported that the Union Ministry of Health and Family Welfare had finally decided to ban the paediatric use of the analgesic, Nimesulide suspension. A notification to this effect was expected soon, following which the drug would be off the shelves

Tizanidine

Tizanidine cont
Tizanidine has been found to be as effective as other antispasmodic drugs and have superior tolerability than baclofen and diazepam.[2] Tizanidine may cause hypotension, so caution is advised when it is used in patients who have a history of orthostatic hypotension. Use caution with this drug as it can be very strong even at the 2 mg dose. Also use caution when switching from gel cap to tablet form and vice versa. Tizanidine can occasionally cause liver damage, generally the hepatocellular type. Clinical trials show that up to 5% of patients treated with tizanidine had elevated liver function test values, though symptoms disappeared upon withdrawal of the drug. Care should be used when first beginning treatment with tizanidine with regular liver tests for the first 6 months of treatment. The tablets are composed of the active ingredient, tizanidine hydrochloride (2.288 mg equivalent to 2 mg tizanidine base and 4.576 mg equivalent to 4 mg tizanidine base), and the inactive ingredients, silicon dioxide colloidal, stearic acid, microcrystalline cellulose and anhydrous lactose.

} The method development for Nizi tablets was by HPLC Method. } The method is yet not developed and is still under development.

Thank You