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PARACETAMOL

CONTENTS

SECTION I PRODUCT CHARACTERISTICS AND SPECIFICATION SECTION II PRODUCT APPLICATIONS SECTION III INDIAN MANUFACTURERS SECTION IV IMPORT/EXPORT LEVEL SECTION V PRICE DETAILS SECTION VI INDIAN DEMAND SECTION VII BROAD OUTLINE OF MANUFACTURING PROCESS SECTION VIII RAW MATERIAL REQUIREMENTS, UTILITY

AND AVAILABILITY SECTION IX GLOBAL SCENARIO SECTION X DISCUSSIONS ON ECONOMIC CAPACITY, PROJECT COST AND PROFITABILITY PROJECTIONS SECTION XI SWOT ANALYSIS SECTION XII FACTORS INFLUENCING THE POSITION FOR

A NEW INDUSTRY AND RECOMMENDATIONS

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SECTION I

PRODUCT CHARACTERISTICS AND SPECIFICATION

General Details Pharmaceutical grade Paracetamol is white. However, on prolonged exposure to air, a grey or pink colour develops. Physical properties: Alternate names Acetaminophen, p-Hydroxy acetanilide, p-acetyl aminophenol,

Acamol, Abensanil Chemical formula C8H9NO2 Appearance White crystalline powder Molecular weight 151.16 Melting point 169 to 170.5 deg.C. PH 5.3 to 6.5 at 25 deg.C. Density 1.293 gm/cc Solubility Very slightly soluble in cold water considerably more soluble in

hot water. It is soluble in methanol ethanol, dimethyl formamide, ethylene dichloride, acetone, ethyl acetate. Slightly soluble in ether. It is insoluble petroleum ethers, pentone, benzene.

Grades and Specification of Paracetamol Generally, two types of Paracetamol are commercially produced namely powder and granules. Purity level: Powder 99.5% Granules 90% The granular grade is called 'direct compressible' product which is easier to use for making tablets . Specification of Paracetamol I.P (Powder) Property Description White crystalline powder slightly bitter in taste Assay <99.53% Solubility About 10% MCOH (as per IP) Identification Confirm to ABCD of IP Melting range 169 to 170 deg.C. pH 10% suspension 5.7 Heavy metals <0.001% 4-amino phenol <0.005% 4-chloro acetanilide <0.001% Loss on drying <0.1256%

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Sulphated ash <0.0715% Specification of Paracetamol Granules B.P. Description White granules or white granular powder

odourless;slightly bitter taste. Assay, % by mass 90.59% as C8H9NO2 Solubility Sparingly soluble in water, freely soluble in alcohol,

very slightly soluble in chloroform and in ether. Identification Test A, IR Absorption spectrum Melting range Between 168 to 172 deg.C. Heavy metals Not more than 20 ppm. 4-aminophenol Not more than 0.005% Related substances By TCL method Sulphated ash Not more than 0.1% Loss on drying Not more than 0.5%

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SECTION II

PRODUCT APPLICATIONS

Paracetamol is used in the treatment of *. Reduction of fever *. Relief of muscle and joint&pain *. Relief of cold and flu symptoms *. Relief of common headache Paracetamol lacks anti inflammatory action in rheumatic disorders. However, it is less toxic than the Aspirin and does not produce anemia and liver damage, which sometimes result from the continued use of acetanilide and acetophenotidine. Paracetamol is also an important intermediate in the manufacture of other pharmaceuticals like the antimalarial amodiaquine. Analgesic Action The analgesic action of Paracetamol involves peripheral

and central influences. Paracetamol is a valuable central analgesic but weak peripheral anti inflammatory agent and exhibits good and prompt antipyretic action. It does not stimulate respiration and causes less gastric irritation and have no effect on cellular metabolism or clotting factors.

Formulations Paracetamol is available as tablets, syrups and injections.

Common side effects Side effects of Paracetamol are rare and usually mild

Usage in pregnant women and nursing mother

Paracetamol is widely used in pregnant women and nursing mothers without any significant adverse effects on the mother or infant.

Usage in infants and children Paracetamol is safe for use in children with appropriate adjustments in dosage as per the weight of the child.

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SECTION III

INDIAN MANUFACTURERS

There are number of manufacturers of Paracetamol in the country. Earlier, most of the units were setup in small scale level with low capacities. In view of the uneconomic capacity, several units where closed in the past. The important manufacturers of Paracetamol include the following * Dinesh Chemicals Pvt. Ltd.

Plot No.3, 4 & 5, G.I.D.C., Nandesari,Baroda-391 340.

* Investa Chemicals

13/2, Rasulpura, Secunderabad-500 010

* Jagson Pal & Co.

20,K.Milestone, Mathura Road, Faridabad-121 003

* Jehovah Laboratories Pvt. Ltd./Jehovah Organics

Kakarolia,Tal.Jambughoda,Dist Panchmahals, Gujarat-389 390

* Joy Pharmaceuticals Labs.

17, Pagnispaga, Indore-4,M.P

* Kumar Pharmaceutical Works Pvt. Ltd.

(At present not in operation) 3/13B,Asafali Road, New Delhi-110 002

* Rajasthan Drugs & Pharmaceuticals Ltd., (A "Miniratna" Enterprises of Govt. of India) Road No.12, V.K.I. Area, Jaipur-302 013,

* Regent Chemicals Ltd. 52, M.I.D.C. Industrial Area, Dhata V, Roha, Dist. Raigad,

Maharashtra.

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* Rohini Chemicals Pvt. Ltd., Regd. Office & Factory Plot No.54/1 & 2, Site IV Sahibabad, Dist. Ghaziabad,

Uttar Pradesh

* Smruthi Organics Ltd. A-165, Balaji Bhavan, 1st Floor, Railway Lines,

Solapur-413 001

* Sarvotham Care Ltd. Corp. Office : 1-20-248, Umajay Complex, Ist Floor, Rasoolpura, Secunderabad-500 003

* Srinivasa Agro Industries & Drugs Pvt. Ltd. D.No.60-3-26/1, Ashok Nagar, Near I.T.I. Bus Stop, Vijayawada - 520 010, A.P.

* Thomson Drugs & Chemicals Aruvacode, Nilambur-679 329. Dist. Malappuram, Kerala.

* Triochem Products Ltd. 10-2,MIDC Indl Estate, Ambernath-421 501. Maharashtra.

* Union Chemicals 14-A,Udyognagar,Udhna,Dist Surat,

Gujarat.

* Vijayalaxmi Drugs & Chemicals Plot No.12, I.D.A., Jeedimetla,Rangareddy,

Andhra Pradesh. Installed capacity of Paracetamol : Around 18000 tonnes per annum

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SECTION IV

IMPORT/EXPORT LEVEL

4.1. Present import level Around 1000 tonnes per annum Countrywise Imports Period April 2001 to March 2002 Country

Quantity in Kgs

Australia 950 Belgium 16320 Chinese Taipei 32400 China P RP 840125 Indonesia 990 Switzerland 81000 UK 19250 USA 325625 Sample of individual imports of Paracetamol Period 2002 Name of the Importers Quantity in

tonnes Value in Rs. Country Date Port

Ajanta Pharma Ltd. 12.000 1059567 China 01.01.2002 to 08.01.2002

Mumbai

Allianz Impex 14.000 1203837 China 01.02.2002 to 09.02.2002

Mumbai

Agog Pharma Ltd. 15.300 1373879 China 01.03.2002 to 08.03.2002

Mumbai

Flamingo Pharmls. 32.000 2777096 China 08.04.2002 to 15.04.2002

Mumbai

Flamingo Pharmls. 16.000 1367088 China 08.05.2002 to 14.05.2002

Mumbai

Flamingo Pharmls. 16.000 1372679 China 03.06.2002 to 10.06.2002

Mumbai

Pan Drugs Ltd. 16.000 1771209 China 01.07.2002 to 05.07.2002

Mumbai

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Anti dumping duty on Paracetamol The Designated Autority in the Commerce Ministry has recommended imposition of definitive anti dumping duty on all imports of Paracetamol originating in or exported from China and Taiwan. Paracetamol is a bulk pharmaceutical active ingredient, displaying analgestic and anti pyretic properties and used in a number of Rx and OTC drug formulation in the form of powders, granules, injectibles and tablets. In its final findings, the authority held that the domestic industry has suffered injury caused by imports from the subject countries, Accordingly, it recommended anti dumping duty, which should be the difference between $3.33 per kg and the landed value of imports in the case of both China and Taiwan. 4.2. Present export level Countrywise Exports Around 1000 tonnes per annum Period April 2001 to March 2002 Country

Quantity in Kgs

Australia 36000 Benin 7800 Burkina Faso 126 Cameroon 24000 Canada 100 Congo P REP 36155 German F REP 158950 Ireland 12000 Israel 1000 Italy 2700 Jordan 15000 Kenya 24500 Korea RP 150 Malaysia 1560 Mayanmar 290 Mexico 33250 Namibia 6900 Netherland 10000 NetherlandAntil 1023 Niger 760

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Nigeria 41100 Pakistan 19050 Philippines 10900 Spain 5000 Sri Lanka 1800 Sudan 12005 Switzerland 32500 Tunisia 24000 Uganda 16500 U Arab Emts 150 UK 261125 USA 168500 Zambia 6700 Sample of individual exports of Paracetamol Period 2002 Name of the Exporters Quantity in

tonnes Value in Rs. Country Date Port

Vamsi Labs P.Ltd. 8.000 875295 Aqaba 01.01.2002 to 16.01.2002

Mumbai

Granules India Ltd. 12.000 1621200 Sydney 01.02.2002 to 15.02.2002

Chennai

Granules India Ltd. 12.000 2369250 Auckland 11.07.2002 to 31.07.2002

Chennai

Newton Pharma 0.100 14550 Dar E Salaam 20.08.2002 to 31.08.2002

Mumbai

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SECTION - V

PRICE DETAILS

Present price level for Paracetamol Around Rs.148 per kg Taxes and duties Extra as applicable

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SECTION VI

INDIAN DEMAND Paracetamol is extensively used in India. There are 174 brand names for Paracetamol in India, which are sold in the market in the formulated form. Therefore, the market is highly competitive Indian demand for Paracetamol 10000 tonnes per annum. Export demand 1000 tonnes per annum Total demand 11000 tonnes per annum In spite of the fact that the adequate capacity for Paracetamol in India, the product is still imported from China, mainly due to the price and credit terms offered. Growth rate in demand It can be reasonably projected that the growth rate in demand for Paracetamol would be in the region of 9 to 10% per annum in the coming years.

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SECTION VII

BROAD OUTLINE OF MANUFACTURING PROCESS Two processes are generally used in the country for the manufacture of Paracetamol. i) From phenol ii) From Paranitrochlorobenzene From phenol The manufacture of Paracetamol involves preparation of para amino phenol as the first step and acetylation of para amino phenol to produce Paracetamol as the next step. Para amino phenol can be prepared from phenol by first converting the phenol to para nitro phenol with sodium nitrite and sulphuric acid and then converting the nitrosophenol to para amino phenol by reduction with sodium sulphide and ammonium carbonate. From Para NitroChloroBenzene 80% of the country's production is presently carried out by the Para nitro chloro benzene route. The process by PNCB route is briefly described below. Para nitro chloro benzene is reacted with caustic soda under pressure of 5 kg/sq.cm and temperature of 150 deg.C for a period of 8 hours in an autoclave. The product of the reaction would be Para nitrol phenol (PNP), which would be separated by crystallisation and filteration. The PNP would be treated with acetic acid to pH level of 3 and then subjected to reduction, for conversion of PNP to para amino phenol (PAP). The Para amino phenol would be acetylated to produce crude Paracetamol. The product would be further bleached with Activated carbon to produce Paracetamol of snow white colour. The product would be then dried in a tray dryer and then ground to the size of 40 microns. The shop floor operations require careful and optimum control to get satisfactory process efficiency and quality levels . Source of technology Central Drug Research Institute, Lucknow, Uttar Pradesh

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Major plant and machinery and suppliers Name of the equipment

Name of the company

Reactor Chemitherm Plants & Systems P. Ltd., 30, Anandha Street Alwarpet, Chennai-600 018 Texel Fabricators Pvt. Ltd., 335, Sidco Industrial Estate, Ambattur, Chennai-600 098, Tamil Nadu

Neutraliser Sharplex Agro Process (I) Pvt. Ltd., 302, Hill View Industrial Estate, LBS Marg Ghatkopar (W), Bombay-400 086

Crystalliser Excel Industrial Services White House, D-111/8,Ist Main Road, Anna Nagar (East) Chennai-600 102 Richard Engineering (Bombay) Pvt. Ltd. 42, IIF, Veerabadran Street Near Valluvar Kottam Nungambakkam, Chennai-600 034

Centrifuge Hydrabad Met Chem. Pvt. Ltd., 34, C.I.E., Phase II, Gandhinagar, Opp. IDPL Colony Hyderabad-500 037 Spark Engineers Pvt. Ltd., 5/332, State Bank Colony II Salem-636 004

Tray dryer Richard Engineering (Bombay) Pvt. Ltd. 42, IIF, Veerabadran Street Near Valluvar Kottam Nungambakkam, Chennai-600 034 Ganson Ltd. 645, Anna Salai, Chennai-600 006

Pulveriser ACE Pack Machines 23, V.N. Industrial Estate Bharathi Colony,Near Athiparasakthi Temple Peelamedu, Coimbatore-641 004

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Frigmaires Engineers PO Box 16353, 8, Janata Industrial Estate Senapati Bapat Marg Opp Phoenix Mill, Lower Parel (W) Mumbai-400 013

Boiler Cethar Vessels Ltd., No.4, Dindigul High Road, Trichy Firetech Boilers Pvt. Ltd. No.211, 2nd Cross, 38th Main, B.T.M. Layout 2nd Stage, Bangalore-68

Refrigeration plant Karna Industries Ltd. 10/67, Industrial Area Kirti Nagar, New Delhi-110 015 Neptune Refrigeration Co. Ltd., 153, Mount Road, Chennai-600 002

Air compressor ELGI Equipments Ltd., Elgi Industrial Complex III, Trichy Road, Singanallur, Coimbatore-641 005 K.G. Khosla Compressors Ltd., 19.8 KMS, Delhi-Mathura Road, Faridabad-121 003, Haryana Kaeser Kompressoren India 9 & 10, Symphony `C' Bldg., Range Hill Road Shivaji Nagar, Pune-411 020

Vacuum pump Southern India Instrumech Pvt. Ltd., 160, Baba Nagar, Villivakkam Chennai-600 049 Travaini-Maneklal Vacuum Technology Pvt. Ltd., Manek Mahal, 7th Floor, 90, Veer Nariman Road, Churchgate, Mumbai-400 020

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Neutch filter Aristo Engineers

J-3, Vikas Udyog Nagar, Behind Kasturi Tiwer Phatak-Goddeo Road, Bhayander (E), Thane-401 105 A.V. Industrial Plastics Corp. 202/Him Shikhar, 1st Floor, Plot No.113 Sector 21, Near Apna Bazar Nerul, Navi Mumbai-400 706 Bifriends Engineering Works Klm College, Sant Narsi Mehta Marg, Parsiwadi, Ghatkopar (W), Mumbai-400 084

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SECTION VIII

RAW MATERIAL REQUIREMENTS, UTILITY AND AVAILABILITY Raw material requirements for Paracetamol production: Basis : One tonne of Paracetamol Para nitrochloro benzene (PNCB) 1.25 tonne Acetic anhydride 0.76 tonne Acetic acid 0.34 tonne Caustic soda 0.75 tonne Iron powder 0.30 tonne Hydrose 0.01 tonne Activated carbon 0.01 tonne Sulphuric acid 0.25 tonne Source of raw material availability Sulphuric acid Coimbatore Pioneers Fertilisers Ltd.,Coimbatore

Activated carbon

Active Carbon India Ltd.,Hyderabad Bleachaid Minerals, Hyderabad Gowrishankar Chemicals, Karnataka Indo German Carbons Ltd.,Kerala Core Carbons Pvt. Ltd. Coimbatore

Caustic soda

Chemfab Alkalies & Chemicals Ltd., Pondicherry SPIC Heavy Chemicals Ltd., Chennai Chemplast, Mettur, Tamil Nadu

Acetic acid EID Parry (India) Ltd.,Madras Trichy Distilleries & Chemicals Ltd.,Senthannipuram, Trichy

PNCB Hindustan Organic Chemicals Ltd., Maharashtra Deepak Nitrite Ltd., Pune

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SECTION IX

GLOBAL SCENARIO International Scenario for Analgesics: Worldwide, the OTC analgesics market is worth $5.5 billion per annum, with 5% per year growth. 40% consumption is in the U.S. 30% in Europe, and 30% in the rest of the world, mainly Japan and South America. Of the three important products, Aspirin and Paracetamol have equal market shares and Ibuprofen has a share half the size. Rhone-Poulenc is the biggest producer worldwide of Aspirin. Mallinckrodt is the biggest producer of Paracetamol worldwide, followed by Hoechst Celanese which has expanded Ibuprofen capacity in Bishop, Texas in a joint"venture with Boots, UK which developed Ibuprofen. Boots has the biggest share of the Ibuprofen market, followed by Ethyl. Global trends for Analgesics Thanks to the trend toward self-medication and the increasing number of consumers over 65, internal analgesics, particularly prescription to over-the-counter products, may be poised for a comeback. In the past few months, there have been several new entrants, starting with Ketoprofen. Both Whitehall-Robins Healthcare and Bayer Consumer Care received the green light from the FDA to sell Ketoprofen as an OTC remedy. Sold in a 12.5 milligram dose, both Orudis KT from Whitehall and Actron from Bayer are expected to be well received, given their ability to provide quick relief with few side effects. These products join the growing number of nonsteroidal anti-inflammatory drugs that are now available in non prescription strength. On a milligram-to-milligram basis, Ketoprofen is said to be the strongest OTC analgesic on the market today. It has four to six hour dosing compared with a product like Aleve that lasts for 12 hours.

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Global market for Paracetamol 60000 tonnes per annum. Market share for analgesics Aspirin 24 percent Paracetamol 46 percent Ibuprofen 22 percent Others 8 percent The international producers of Paracetamol * Mitsui Pharmaceuticals Inc.,

12-2, Nihonbashi 3-chome, Chuo-ku, Tokyo 103

* Mitsui Toatsu Chemicals Inc.,

2-5 Kasumigaseki, 3-chome, Chiyoda-ku, Tokyo-100

* Asiamerica International Inc.,

P.O.Box 22281, Fort Lea, NJ 07024 * Alfa Chem

98, Kings Point Road, Great Neck, NY 11024-1303

* Graymor Chemical Co. Inc.,

40 Parker Road, Suite 210, Elizabeth, NJ 07208

* �Hoechst Celanese Corporation

Post Box No.428, Bishop, Texas TX 78343

* Rhone- �Poulenc North American Chemicals

Rhone-Poulenc Pharmaceutical Ingredients CN 7500, Cranbury, NJ 08512-7500

SECTION X

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DISCUSSIONS ON ECONOMIC CAPACITY, PROJECT COST AND

PROFITABILITY PROJECTIONS Economic capacity 240 tonnes per annum Project cost Rs. 215 lakhs Assessment of project cost 1. Land S.No. Description Cost

Rs.in lakhs 1.1 Cost of land of one acre at Rs.5.5 lakh per acre 5.5 1.2 Cost of levelling, laying internal roads/fencing and

compound wall

0.55

Subtotal 6.05 2. Building S.No. Description Cost

Rs.in lakhs 2.1 Factory building of area 620 sq.m. at Rs.3200/sq.m. 19.84 2.2 Non-factory building of area 60 sq.m.at Rs.4500/sq.m. 2.70 Subtotal 22.54 3. Cost of Plant & Machinery S.No. Description Cost

Rs.in lakhs 3.1 Cost of basic plant and machinery 75 3.2 Instrumentation and control 5.63 3.3 Pipelines and valves 7.5 3.4 Structurals for erection 3.75 Subtotal 91.88 3.5 Octroi, excise duty, sales tax, etc.at 12%� 11.03 3.6 Packaging and insurance charges (2%) 1.84 3.7 Transportation charges (2%) 1.84 3.8 Machinery stores and spares (2%) 1.84 3.9 Foundation charges (2%) 1.84 3.10 Installation charges (2%) 1.84 Total cost of plant and Machinery 112.11 4. Technical know-how fees Rs.2.5 lakhs

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5. Miscellaneous fixed assets S.No. Description Cost

Rs.in lakhs 5.1. Electrification 4 5.2. Steam boiler and auxillaries 4 5.3. Water storage tank, borewell etc. 1 5.4. Fuel storage tank 2 5.5. Laboratory equipment 0.8 5.6. Office machinery & equipment 1.6 5.7. Material handling equipment, packaging machinery,

weigh balance, etc. 1.5

5.8. Diesel generator 4.5 5.9. Effluent treatment 1.4 Total 20.8 6. Preliminary & Pre-operative expenses: S.No. Description Cost

Rs.in lakhs 6.1. Preliminary expenses 0.8 6.2. Pre-operative expenses:- - 6.2.1 Establishment 0.8 6.2.2 Rent rates and taxes 0.8 6.2.3 Travelling expenses 1.2 6.2.4 Interest and commitment charges on borrowings 7.2 6.2.5 Insurance during construction period 3.5 6.2.6 Other preoperative expenses and deposits - 6.2.7 Interest on deferred payment - Total 14.3 7. Provision for contingency Rs.11.17 lakhs 8. Working capital margin Rs. 26.25 lakhs 9. Total project cost Rs.215 lakhs 10. Means of Finance Promoter's contribution Rs.86 lakhs Term loan from financing institutions Rs.129 lakhs Total project cost Rs.215 lakhs 11. Financial statements

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Cost of production A Variable cost

Rs. in lakhs

Raw material and utilities 194.32 Spares and maintenance 6.73 Selling expenses 17.76 Total variable cost (A)

218.81

B Fixed cost

Salaries and wages 18 Interest on term loan and working capital loan 37.38 Depreciation 14.46 Administrative expenses 10.66 Total fixed cost (B)

80.5

C. Total cost of production (A+B)

299.11

D. Selling price per kg. (in Rupees)

148

E. Annual sales turnover

355.2

F. Net profit before tax (E-C)

55.89

G. Breakeven point in %

59%

SECTION XI

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SWOT ANALYSIS

Strength Steady growth in demand, due to higher

investment in health care in the country

Weakness Competitive product

Opportunity Export market

Threat Mushroom growth

SECTION XII

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FACTORS INFLUENCING THE POSITION FOR A NEW INDUSTRY

Paracetamol is currently the safest and most widely used agent in the treatment of fever, muscle and body aches, flu and cold symptoms. Its side effect are few. It is economical and effective. The demand for Paracetamol is likely to go up steadily in the coming years due to the following reasons. * Increasing percentage of ageing population in the country and consequent increasing demand for Analgesics. * Low cost of the drug * Absence of side effects * Popularity of the drug due to reputation gained during long years of use. * Paracetamol has maintained its market share inspite of the competitive analgesics that have emerged in the market. The export market for Paracetamol is likely to maintain its growth trends, since the Indian units are competitive in the global market in terms of quality and product specifications. Considering the above facts, strong case exists to create additional capacity for Paracetamol in the country, to meet the growing demand in the coming years.