M/s. S. M. Labs (P) Ltd., Unit - IIIenvironmentclearance.nic.in/writereaddata/form-1/0_0_09_Dec_2013... · M/s. S. M. Labs (P) Ltd., Unit - III Prepared by Rightsource Industrial

M/s. S. M. Labs (P) Ltd., Unit - III

Prepared by Rightsource Industrial Solutions Pvt Ltd

LIST OF CONTENTS

S. No Content Name Page No’s

1 Form -I 1-12

2 List of Products 13

3 List of By-products 14

4 List of Raw Materials 15-24

5 Process Description 25-99

6 Water Consumption Details 100

7 Waste water Details 101-102

8 ETP Flow Chart 103

9 Solid Waste Details 104-105

10 Stack Emission Details 106-107

11 Process Emission Details 108

12 Spent Solvents 109-110

13 Freasibility Report 111-113

14 Draft TOR 114-116

15 Project Report 117-131

ENCLOSURES

16 Pollution Load Details Enclosed

17 Topo Map Enclosed

18 Site Plan Enclosed

19 Land Document Enclosed

20 Consultant Details Enclosed


Prepared by Rightsource Industrial Solutions Pvt Ltd. 1

APPENDIX-I

FORM -1

I) Basic information S. No ITEM DETAILS 1. Name of the project/s M/s. S. M. Labs (P) Ltd., Unit - III 2. S.No.in the schedule 5 (f) 3. Proposed capacity

/area/length/tonnage to be handled/command area/lease area/ number of wells to be drilled

Proposed production capacity - 1600.00 Kg/Day. Source of water : Bore well water and water tankers Total project area : 28327.78 SQM

4 New/Expansion/Modernization New 5. Existing Capacity/Area etc. New

6. Category of Project i.e.’ A’ or ‘B’ A 7. Does it attract the general

condition? If yes, please specify. No

8. Does it attract the specific condition? If yes, please specify.

No

9. Location Sy. No. 1058,1059,Manchanapally (V), Bommalaramaram(M),Nalgonda (Dt) Andhra Pradesh.

10. Nearest railway station/airport along with distance in kms.

Bhongiri – 18KMs Hyderabad(Shamshabad Air port) – 70 Kms National High way – No:202 (Warangal – Hyderabad)

11. Nearest Town, City, District Headquarters along with distance in kms.

Bhongiri – 18Kms Nalgonda – 80 Kms

12. Village Panchayats, Zilla Parishad, Municipal Corporation, Local Body (Complete postal addresses with telephone nos. to be given)

Village Panchayat Manchanapally (V), Bommalaramaram(M),Nalgonda (Dt)

13. Name of the applicant G. Manikya Reddy 14. Registered Address M/s S. M. Labs (P) Ltd., Unit - III

Plot No.C-5, IDA, Moula Ali Hyderabad-500040.

15. Address for correspondence: Rightsource Industrial Solutions Pvt. Ltd. Plot No.203, H.No.5-36/203,Prashanti nagar, IDA, Kukatpally, Hyderabad-500072.

Name G. Manikya Reddy Designation

(Owner/Partner/CEO) Executive Director

Address M/s. Rightsource Industrial Solutions Pvt. Ltd. Plot No.203, H.No.5-36/203,Prashanti nagar, IDA, Kukatpally, Hyderabad-500072



Pin Code 500072

E-mail [email protected] [email protected]

Telephone No. 040-23075699, 40126589 Fax No. 040-23070602 16. Details of alternative sites

examined, if any. Location of these sites should be shown on a topo sheet

N.A.

17. Interlinked Projects Nil 18. Whether separate application of

interlinked project has been submitted?

N.A.

19. If Yes, date of submission N.A. 20. If no, reason N.A. 21. Whether the proposal involves

approval/clearance under: if yes, details of the same and their status to be given. (a) The Forest (Conservation) Act, 1980? (b) The Wildlife (Protection) Act, 972? (c) The C.R.Z Notification, 1991?

Nil

22. Whether there is any Government Order/Policy relevant/relating to the site?

Nil

23. Forest land involved (hectares) NIL 24. Whether there is any litigation

pending against the project and/or land in which the project is propose to be setup? (a) Name of the court (b) Case No. (c) Orders/directions of the Court, if any and its relevance with the proposed project.

NIL

mailto:[email protected]�



II) Activity 1. Construction, operation or decommissioning of the Project involving actions,

which will cause physical changes in the locality (topography, land use, changes in water bodies, etc.)

S. No Information/Checklist confirmation

Yes/No Details thereof(with approximate quantities/rates, wherever possible)with source of information data

1.1 Permanent or temporary change in land use, land cover or topography including increase in intensity of land use (with respect to local land use plan)

Yes Permanent change in the land use. Construction of Buildings for manufacturing of Bulk Drugs & Intermediates in 7 Acres (28327.78 SQM) of land.

1.2 Clearance of existing land, vegetation and buildings?

No None

1.3 Creation of new land uses?

Yes Total Plot Area : 28327.78 SQM Green Belt : 17864.94 SQM

1.4 Pre-construction investigations e.g. bore houses, soil testing?

Yes Bore well water and Soil.

1.5 Construction works? Yes Production Block-I : 557.174 SQM Production Block-II: 557.174 SQM Boiler House &Coal Shed : 185.77 SQM Site paln Enclosed

1.6 Demolition works? No NA 1.7 Temporary sites used for

construction works or housing of construction workers?

No No temporary or permanent housing facilities will be provided. All labors will come from nearby villages.

1.8 Above ground buildings, structures or earthworks including linear structures, cut and fill or excavations

No None

1.9 Underground works including mining or tunneling?

No Not envisaged. No Mining or Tunneling Works.

1.10 Reclamation works? No Not envisaged. No Reclamation Works 1.11 Dredging? No No Dredging Work. 1.12 Offshore structures? No No Offshore Works. 1.13 Production and manufacturing

processes? Yes Enclosed

1.14 Facilities for storage of goods or materials?

Yes Storage area will be used for storage of goods and materials during operation phase.

1.15 Facilities for treatment or disposal of solid waste or liquid effluents?

Yes Municipal Solid Waste will be collected and segregated & handed over to local authorized body for further disposal Domestic effluent will be treated in Septic tanks & Soak pits. Effluent will be treated in ETP



ETP sludge & Hazardous waste will be sent to TSDF for further disposal.

1.16 Facilities for long term housing of operational workers?

No No housing facilities will be provided for operational workers. Most of the workers are locals and nearby villages.

1.17 New road, rail or sea traffic during construction or operation?

No Not envisaged.

1.18 New road, rail, air, waterborne or other transport infrastructure including new or altered routes and stations, ports, airports etc?

No Not envisaged.

1.19 Closure or diversion of existing transport routes or infrastructure leading to changes in traffic movements?

No

Not envisaged.

1.20 New or diverted transmission lines or pipelines?

No Not envisaged.

1.21 Impoundment, damming, culverting, realignment or other changes to the hydrology of watercourses or aquifers?

No No

1.22 Stream crossings? No There is no stream passing through the site.

1.23 Abstraction or transfers of water from ground or surface waters?

Yes Water requirement will be met from the Bore well and water tankers supply.

1.24 Changes in water bodies or the land surface affecting drainage or run-off?

No There will not be any changes in water bodies or the land surface affecting drainage or run-off.

1.25 Transport of personnel or materials for construction, operation or decommissioning?

No NA

1.26 Long-term dismantling or decommissioning or restoration works?

No No dismantling or decommissioning or restoration works

1.27 Ongoing activity during decommissioning which could have an impact on the environment

No

NA

1.28 Influx of people to an area in either temporarily or permanently?

Yes Workers /Employees will be increased and the working hours are in shifts / general.

1.29 Introduction of alien species? No No Introduction of alien species 1.30 Loss of native species or

genetic diversity? No No Loss of native species or genetic

diversity 1.31 Any other actions?

No __



2. Use of Natural resources for construction or operation of the Project (such as land, water, materials or energy, especially any resources which are non-renewable or in short supply)

S. No Information/Checklist

confirmation Yes/N

o Details thereof (with approximate quantities/rates, wherever possible) with source of information data

2.1 Land especially undeveloped or agricultural land (ha)

No Nil

2.2 Water (expected source & competing users) unit: KLD

Yes 128.56KLD Source of water: Bore well and water tankers.

2.3 Minerals (MT) No No Minerals required 2.4 Construction material – stone,

aggregates, sand/soil (expected source (MT)

No NA

2.5 Forests and timber (source MT)

No No Timber will be used.

2.6 Energy including electricity and fuels (source, competing users) Unit: fuel (MT), energy (MW)

Yes • Electricity–850 H.P - From APCPDCL

• Generator: 250 KVA - 2 No’s Fuel: HSD about 200 Liters per day

• Steam: Boiler: (Coal Fired) 4.0TPH - 2 No’s

• Fuel: Coal :20.0TPD

2.7 Any other natural resources (use appropriate standard units)

No None



2. Use, storage, transport, handling or production of substances or materials, which could be harmful to human health or the environment or raise concerns about actual or perceived risks to human health.


confirmation Yes/No Details thereof (with approximate

quantities/rates, wherever possible)with source of information data

3.1 Use of substances or materials, which are hazardous (as per MSIHC rules) to human health or the environment (flora, fauna, and water supplies)

Yes Enclosed list of hazardous chemicals are used in the products. Hazardous Chemicals are stored as per manufacture, storage and import of hazardous chemical rules 1989.

3.2 Changes in occurrence of disease or affect disease vectors (e.g. insect or water borne diseases)

No Effluent will be sent to ETP-ZLD System. All solid wastes will be stored in the covered platform with leachate collection system and sent to TSDF / Authorized agencies. Process emissions will be scrubbed in the scrubbers.

3.3 Affect the welfare of people e.g. by changing living conditions?

No Not applicable .

3.4 Vulnerable groups of people who could be affected by the project e.g. hospital patients, children, the elderly etc.,

No None

3.5 Any other causes

No Nil

3. Production of solid wastes during construction or operation or decommissioning

(MT/month) S. No Information/Checklist


quantities/rates, wherever possible) with source of information data

4.1 Spoil, overburden or mine wastes

No No Spoil, overburden or mine wastes

4.2 Municipal waste (domestic and or commercial wastes)

Yes Municipal Solid Waste will be collected segregated & Disposed to authorized party for further disposal. The commercial waste from the administration building is generated and is to scrap vendors.

4.3 Hazardous wastes (as per Hazardous Waste Management Rules)

Yes Details of hazardous wastes generated from the enhanced capacities /load /are given.

4.4 Other industrial process wastes

Yes Details of the industries process wastes from the enhances capacities /load are given.



5. Release of pollutants or any hazardous, toxic or noxious substances to air (Kg/hr) S. No Information/Checklist



5.1 Emissions from combustion of fossil fuels from stationary or mobile sources

Yes About 20.0 TPD Coal will be used in Boiler and about 200/liters/day diesel will be used in D.G. sets emission details are given.

5.2 Emissions from production processes.

Yes 219.33 Kg/day from all the products.

5.3 Emissions from materials handling including storage or transport

Yes Pumps will be used for handling of liquid raw materials and trolleys will be used for solid / powder type raw materials Vent condensers are provided for all storage tanks, centrifuges, catch pots.

5.4 Emissions from construction activities including plant and equipment

Yes It will be temporary during the construction of the project.

5.5 Dust or odors from handling of materials including construction materials, sewage and waste

Yes Dust will be generated due to construction activities and transportation of goods and materials. It will be reduced by handling as per MSDS and water will be sprayed at construction waste and on roads.

5.6 Emissions from incineration of waste

No No incineration of waste in the site

5.7 Emissions from burning of waste in open air (e.g. slash materials, construction debris)

No No burning activity in the site. No emissions will generate

5.8 Emissions from any other sources.

No None

4.5 Surplus product

No Surplus production is not envisaged since production will be as per the market demand only.

4.6 Sewage sludge or other sludge from effluent treatment

Yes Domestic waste water sent to septic tank and overflow to ETP. ETP sludge generation details are given

4.7 Construction or demolition wastes

No No demolition waste will be generated.

4.8 Redundant machinery or equipment

No Not envisaged

4.9 Contaminated soils or other materials

No Not envisaged

4.10 Agricultural wastes No Not Applicable

4.11 Other solid wastes

No Details of other solid waste are given.



6. Generation of Noise and Vibration, and Emissions of Light and Heat




6.1 From operation of equipment e.g. engines, ventilation plant, crushers

Yes Noise will be generated from the utilities section. Silencers will be provided for D.G. Sets.

6.2 From industrial or similar processes

Yes Noise from process utilities will be within the limits. About 56dB(A)

6.3 From construction or demolition

No No construction will taken place.

6.4 From blasting or pilling

No None, No blasting or pilling during construction

6.5 From construction or operational traffic

No None

6.6 From lighting or cooling systems

No Negligible.

6.7 From any other sources No Nil

7. Risks of contamination of land or water from releases of pollutants into the ground or into sewers, surface waters, groundwater, coastal waters or the sea: S. No Information/Checklist



7.1 From handling, storage, use or spillage of hazardous materials

Yes Spillages such as wastewater /solid wastes/raw material are possible and the risk of this would be limited to within the premises of the manufacturing facilitate. Precautionary measures are implementing in the existing permitted industry and will continue for spillage control and to avoid contamination of land or water from the pollutants or raw materials. Suggestions from the safety consultants will be followed to avoid the risk and prevent accidents.

7.2 From discharge of sewage or other effluents to water or the land (expected mode and place of discharge)

Yes 2.00 KLD Domestic sewage will be sent to soak pit. Process effluent will be treated and evaporated and recycled within the plant.

7.3 By deposition of pollutants emitted to air into the land or into water

Yes Possibility of deposition of pollutants emitted to air into the land / water can’t be ruled out and the precautions taken by the industries to control such emissions by adopting the suitable controlling equipment will be provided such as Bag filters, Scrubbers etc.

7.4 From any other sources No Process emissions are controlled by



scrubbers. 7.5 Is there a risk of long term

build up of pollutants in the environment from these sources?

No Not envisaged. Industry will implement all latest pollution control equipment and will adopt them build up of pollutants in the environment from the industrial activity.

8. Risk of accidents during construction or operation of the Project, which could affect human health or the environment

9. Factors which should be considered (such as consequential development) which could lead to environmental effects or the potential for cumulative impacts with other existing or planned activities in the locality. S. No Information/Checklist



9.1 Lead to development of supporting laities, ancillary development or development stimulated by the project which could have impact on the environment e.g. * Supporting infrastructure (roads, power supply, waste or waste water treatment, etc.) * Housing development

Yes

No

Supporting infrastructure such as roads, power supply, waste or waste water treatment etc. may be impacts on the project activities however the impact from such activates will be limited. No roads will be laid, since plant site is well connected to road. Power supply will be obtained from public supply and there will not be any effect on the environment .Waste water generation from the process will be treated and reused, waste water treatment plant will be constructed and there will not

S. No Information/Checklist confirmation

Yes/No Details thereof (with approximate quantities/rates, wherever possible) with source of information data

8.1 From explosions, spillages, fires etc from storage, handling, use or production of hazardous substances

Yes All the safety precautions will be taken by the industry to avoid such accidents.

8.2 From any other causes

Yes Static Electricity

8.3 Could the project be affected by natural disasters causing environmental damage (e.g. floods, earthquakes, landslides, cloudburst etc)?

No Not envisaged.



* Extractive industries * Supply industries * Other

No

Yes

No

be any impact on the environment. Not envisaged .possibility of extractive industries cannot be ruled out. Not envisaged. Not envisaged.

9.2 Lead to after-use of the site, which could have an impact on the environment

No Not envisaged.

9.3 Set a precedent for later developments

No Not envisaged.

9.4 Have cumulative effects due to proximity to other existing or planned projects with similar effects

No Marginal cumulative effects envisaged.

10. Environmental Sensitivity S. No Areas Name/

Identity Aerial distance (within 25 km) Proposed project location boundary

1 Areas protected under international conventions, national or local legislation for their ecological, landscape, cultural or other related value

No Note envisaged .There is no Eco sensitive area near the plant site.

2 Areas which are important or sensitive for ecological reasons – Wetlands, watercourses or other water bodies, coastal zone, biospheres, mountains, forests

No Not envisaged .There is no wetland near the plant site.

3 Areas used by protected, important or sensitive species of flora or fauna for breeding, nesting, foraging, resting, over wintering, migration

No Not envisaged.

4 Inland, coastal, marine or underground waters

No Nil



5 State, National boundaries

No None with in 10 KM radius

6 Routes or facilities used by

the public for access to recreation or other tourist, pilgrim areas

No Not envisaged.

7 Defense installations

No No defense establishments within the area.

8 Densely populated or built-up area

No ---

9 Areas occupied by sensitive man-made land uses (hospitals schools, places of worship, community facilities)

No There is no habitation /sensitive, manmade, land used within the specified distance.

10 Areas containing important, high quality or scarce resources (ground water resources, surface resources, forestry, agriculture, fisheries, tourism, minerals).

No NA

11 Areas already subjected to pollution or environmental damage. (Those where existing legal environmental standards are exceeded)

No N A

12 Areas susceptible to natural hazard which could cause the project to present environmental problems (earthquakes, subsidence, landslides, erosion, flooding or extreme or adverse climatic conditions)

No Not envisaged.




Prepared by Rightsource Industrial Solutions Pvt Ltd 13

LIST OF PRODUCTS

S. No Name of the Product CAS No's Quantity In Kg/Month

Quantity In Kg/Day

1 Metformin Hydrochloride 1115-70-4 20000.00 666.67 2 5-Cyano Pthalamide 82104-74-3 10000.00 333.33 3 Atorvastatin Calcium 134523-03-8 2000.00 66.67 4 Lansoprazole 103577-45-3 3000.00 100.00 5 Sildenafil Citrate 171599-83-0 2000.00 66.67 6 Zidovudine 30516-87-1 2000.00 66.67 7 Levocetirizine Di Hydrochloride 130018-87-0 2000.00 66.67 8 Escitalopram Oxalate 219861-08-2 2000.00 66.67 9 Lamivudine 134678-17-4 2000.00 66.67

10 Losartan Potassium 12470-99-8 3000.00 100.00 Total 48000.00 1600.00



LIST OF BY-PRODUCTS

S. No Name of the By-Product Quantity In Kg/Day

1 Thioacetic acid 26.67 2 Trityl alcohol 60.70 3 Triethyl methane sulfonate 26.67 4 Trityl methyl ether 35.89

M/s. S.M.Labs Pvt. Ltd., Unit - III


METFORMIN HDYROCHLORIDE

LIST OF RAW MATERIALS

S.No. Raw Material Consumption/ Batch in Kgs

Consumption/ Day in Kgs

1 Dimethyl amine Hcl 630.00 4200.00 2 Dicyandiamide 650.00 4333.33 3 Xylene 1550.00 10333.33 4 Activated carbon 2.00 13.33 5 Hyflo 2.00 13.33 6 Methanol 440.00 2933.33



5-CYANO PHTHALIDE




1 5-Carboxy Phthalic Acid 115.00 383.33 2 Thionyl Chloride 76.80 256.00 3 Toluene 1000.00 3333.33 4 Ammonia 30.00 100.00 5 Thionyl Chloride 75.20 250.67



ATORVASTAIN CALCIUM




1 Tert-Butyl-2-[(4R,6S)]-6-(cyanomethyl)-2,2-dimethyl-1,3-Dioxan-4-yl] acetate

66.40 44.27

2 Palladium carbon 1.20 0.80 3 Methanol 1016.00 677.33 4 Hydrogen 5.00 3.33 5 Aniline 27.20 18.13 6 Dimethyl Carbonate 27.20 18.13 7 2-Methyl-2-Butanone 27.20 18.13 8 Sulfuric Acid 0.80 0.53

10 Benzaldehyde 27.60 18.40 11 Potassium carbonate 5.00 3.33 12 Acetone 140.00 93.33 13 Toluene 740.00 493.33 14 Fluorobenzaldehyde 28.80 19.20 17 Paratoluene sulfonic acid 2.00 1.33 18 IPA 720.00 480.00 19 Sulfuric Acid 2.40 1.60 21 Calcium Acetate 15.00 10.00 23 Activated Carbon 2.00 1.33



LANSOPRAZOLE




1 2,3-Lutidine 46.00 46.00 2 Acetic Acid 64.00 64.00 3 Hydrogen Peroxide (50%) 55.00 55.00 4 Sulfuric Acid 108.00 108.00 5 Nitric Acid 30.00 30.00 6 Sodium Hydroxide 60.00 60.00 7 Potassium Carbonate 53.00 53.00 8 Tri Fluoro Ethanol 39.00 39.00 9 MIBK 130.00 130.00

10 Acetic Anhydride 130.00 130.00 11 TEBAC 1.00 1.00 12 Toluene 460.00 460.00 13 Hydrogen Chloride Gas 14.00 14.00 14 Activated Carbon 3.00 3.00 15 Methylene Dichloride 175.00 175.00 16 Thionyl Chloride 41.00 41.00 17 2-Mercapto Benzimidazole 49.00 49.00 18 Isopropyl Alcohol 250.00 250.00 19 Catalyst 1.00 1.00 20 Chloroform 465.00 465.00 21 Acetone 125.00 125.00



SILDENAFIL CITRATE




1 4-Amino-1-methyl-3-n-propyl pyrazole-5-carboxamide

29.50 19.67

2 2-Ethoxy-5-(4methylpiperazinyl) sulfonyl benzoic acid

53.10 35.40

3 Thionyl chloride 19.30 12.87 4 Ammonia 2.80 1.87 5 DMF 0.50 0.33 6 MDC 300.00 200.00 7 Sodium sulfate 20.00 13.33 8 Petroleum ether 60.00 40.00 9 Potassium hydroxide 10.00 6.67

10 Hydrochloric acid (30%) 21.70 14.47 11 t-Butanol 300.00 200.00 12 Citric acid 29.50 19.67 13 Acetone 300.00 200.00



ZIDOVUDINE




1 β-Thymidine 70.00 46.67 2 1,4-Dioxane 700.00 466.67 3 Tri ethyl amine 23.00 15.33 4 Trityl chloride 64.00 42.67 5 Toluene 3620.00 2413.33 6 Methyl sulfonyl chloride 26.00 17.33 7 Tri ethyl amine 50.00 33.33 8 Methanol 1500.00 1000.00 9 Sodium azide 14.00 9.33

10 Ammonium chloride 12.00 8.00 11 DMSO 600.00 400.00 12 PTSA Monohydrate 34.00 22.67 13 Sodium carbonate 10.00 6.67 14 Ethyl Acetate 1300.00 866.67 15 Activated Carbon 5.00 3.33



LEVO CETIRIZINE DI HYDROCHLORIDE




1 p-chloro benzo phenone 120.00 80.00 2 Ammonium formate 35.00 23.33 3 Hydrochloric acid 25.00 16.67 4 Toluene 1600.00 1066.67 5 Activated carbon 20.00 13.33 6 Sodium hydroxide 50.00 33.33 7 Tartaric acid 32.00 21.33 8 MDC 1650.00 1100.00 9 para toluene sulphonyl

chloride 52.00 34.67

10 n,n-bis( 2-chloro ethyl)amine HCl

50.00 33.33

11 Ethyl di isopropyl amine 28.00 18.67 12 Methanol 400.00 266.67 13 Hydro bromic acid 23.00 15.33 14 Acetic acid 15.00 10.00 15 Chloro ethanol 20.00 13.33 16 Triethyl amine 24.70 16.47 17 Sodium mono chloro acetate 27.00 18.00 18 Hydrochloric acid 17.00 11.33 19 Di methyl formamide 100.00 66.67 20 Acetone 100.00 66.67



ESCITALOPRAM OXALATE




1 4-[4-Dimethylamino-1-(4-fluoro-phenyl)-1-hydroxy-butyl]-3-hydroxy methyl-benzonitrile HBr

120.00 80.00

2 D-P-Toluyl-D-Tartaric Acid 48.00 32.00 3 Sodium hydroxide (20%) 200.00 133.33 4 Toluene 700.00 466.67 5 Isopropyl Alcohol 500.00 333.33 6 Methane Sulfonyl Chloride 28.50 19.00 7 Triethyl amine 25.00 16.67 8 MDC 1200.00 800.00

10 Oxalic Acid 32.00 21.33 11 Acetone 450.00 300.00 12 Activated Carbon 10.00 6.67



LAMIVUDINE




1 L(+ )Menthol 82.60 55.07 2 Glyoxalic Acid (35%) 112.00 74.67 3 Sodium Bisulfate 63.00 42.00 4 Sodium Carbonate 15.00 10.00 5 Formaldehyde 16.00 10.67 6 Sulphuric Acid 3.00 2.00 7 Cyclohexane 1100.00 733.33 8 2,5 Diethane 80.00 53.33 9 Acetic Acid 43.00 28.67

10 Triethyl Amine 3.00 2.00 11 Toluene 1010.00 673.33 12 n-Hexane 430.00 286.67 13 Activated Carbon 5.00 3.33 14 Hyflow 5.00 3.33 15 Cytosine 58.55 39.03 16 HMDS 15.00 10.00 17 Thioinyl Chloride 63.00 42.00 18 Dimethylformamide 54.00 36.00 19 Triethyl amine 102.00 68.00 20 MSA 1.00 0.67 21 Methylene Dichloride 1100.00 733.33 22 Ethyl Acetate 150.00 100.00



LOSARTAN POTASSIUM




1 2-Cyano-4-Methyl biphenyl (OTBN)

60.00 60.00

2 Sodium Azide 22.00 22.00 3 TEA HCl 25.00 25.00 4 Hydrochloric acid 23.00 23.00 5 Sodium nitrite 23.00 23.00 6 Toluene 400.00 400.00 7 Trityl chloride 83.00 83.00 8 TEA 30.00 30.00 9 MDC 400.00 400.00

10 Methanol 1300.00 1300.00 11 N-Bromosuccinimide (NBS) 45.00 45.00 12 Sodium meta bisulphate 10.00 10.00 13 Methylenedichloride 400.00 400.00 14 Ethyl Acetate 200.00 200.00 15 Butyl chloro formyl imidazole

(BCFI) 45.00 45.00

16 TBAB 5.00 5.00 17 IPA HCl 300.00 300.00 18 Sodium hydroxide 27.00 27.00 19 Potassium hydroxide 20.00 20.00 20 Activated Carbon 15.00 15.00



1. METFORMIN HDYROCHLORIDE

Process Description:

Stage-1

Dimethyl amine Hydrochloride reacts with Dicyandiamide in the presence of Xylene and

Methanol as a solvent media to give Metformin Hydrochloride as product.




Route of synthesis:

Stage-1:

Dimethylamine Hydrochloride

HN

CH3H3CH

Cl

C2H8ClN

81.54

+

Dicyanodiamide

H2N NH2

NCN

C2H4N4

84.07

H3CN

H3C

NH

NH

NH2

NH HCl

C4H12ClN5

165.62

Metformin Hydrochloride

Xylene




Flow Chart:

Stage-1Dimethyl amino HydrochlorideDicyandiamideXylene

Xylene Rec

METFORMIN HYDROCHLORIDE



METFORMIN HYDROCHLORIDE

Material Balance:

Material Balance of Metformin Hydrochloride Stage-1

Batch Size: 1250Kg Name of the input Quantity

in Kg Name of the out put Quantity

in Kg Dimethyl amine Hcl 630.00 Metformin Hydrochloride 1250.00 Dicyandiamide 650.00 Xylene Recovery 1500.00 Xylene 1550.00 Xylene Loss 50.00 Activated carbon 2.00 Methanol Recovery 410.00 Hyflo 2.00 Methanol Loss 22.00 Methanol 440.00 Effluent water 2315.00 Water 2300.00 (Water-2300,Methanol-5,Dimethyl

Amine Hydrochloride-10)

Spent carbon + Hyflo 4.00 Organic Residue 23.00 (Organic Impurities-20,Methanol-

3,)

Total 5574.00 Total 5574.00



2. 5-CYANO PHTHALIDE


Stage-1

1-Oxo-1,3-dihydro-2-benzofuran-5- carboxylic acid reacts with thionyl chloride and ammonia Gas to get Stage-1 Product.

Stage-2

Stage-1 product reacts with thionyl chloride to get 5-Cyano phthalide as Product.



5-CYANO PHTHALIDE

Route of synthesis:

Stage-1:

1-Oxo-1,3-dihydro-2-benzofuran-5-carboxylic acid

O

O

OH

O+ SOCl2 + NH3

Thionyl Chloride Ammonia

1-Oxo-1,3-dihydro-2-benzofuran-5-carboxamide

O

O

NH2

O

C9H7NO3

177.16

Sulphur dioxide Hydrochloric acid

+ SO2 + 2HCl

C9H6O4

178.14

118.97 17.03

64.06 2X36.5=73.0



Stage-2:

1-Oxo-1,3-dihydro-2-benzofuran-5-carboxamide

O

O

NH2

O

C9H7NO3

177.16

1-Oxo-1,3-dihydro-2-benzofuran-5-carbonitrile

O

NO

C9H5NO2

159.14

+ SOCl2

Thionyl Chloride

118.97

SO2+ 2HCl

64 2X36.5=73Sulfurdioxide Hydrochloric Acid

+



5-CYANO PHTHALIDE

Flow-Chart:

Stage-1

Stage-2

5-carboxy phthalic acidThionyl chlorideAmmonia

Sulphur d ioxide

Stage-1Thionyl chloride

Sulphuric acid

5-CYANO PHTHALIDE



5-CYANO PHTHALIDE

Material Balance:

Material Balance of 5-Cyano phthalide Stage-1

Batch Size:100Kg Name of the input Quantity


in Kg 5-Carboxy Phthalic Acid 115.00 Stage-1 112.00 Thionyl Chloride 76.80 Toluene Recovery 474.00 Toluene 500.00 Toluene Loss 25.00 Ammonia 30.00 Effluent water 148.12 Water 100.00 (Water-100,Ammonium chloride-

47.12,Toluene-1)

Process Emission 41.35 (Sulfur dioxide) Organic Residue 21.33 Total 821.80 Total 821.80

Material Balance of 5-Cyano phthalide Stage-2



in Kg Stage-1 112.00 5-Cyano Phthalide 100.00 Thionyl Chloride 75.20 Toluene Recovery 475.00 Toluene 500.00 Toluene Loss 25.00 Hydrochloric acid Reuse 46.15 Process Emission 40.45 (Sulfur dioxide) Organic Residue 0.60 Total 687.20 Total 687.20



3. ATORVASTAIN CALCIUM


Stage-1

Tert-Butyl-2-[(4R,6S)-6-(cyano methyl)-2,2-dimethyl-1,3-dioxan-4-yl] acetate reduction with Hydrogen on Palladium Carbon in presence of Methanol gives tert-Butyl-2-[(4R,6S)-6-(amino ethyl)-2,2-dimethyl-1,3-dioxan-4-yl] acetate.

Stage-2

Aniline on condensed with Dimethyl Carbonate and 2-Methyl-2-butanone in presence of Methanol gives 4-Methyl-3-oxo-N-Phenyl pentanamide.

Stage-3

4-Methyl-3-oxo-N-phenyl pentanamide upon reaction with Benzaldehyde in presence of Potassium Carbonate, Acetone and Toluene media gives 2-Benzylidene-4-methyl-3-oxo pentanoic acid phenyl amide.

Stage-4

2-Benzylidene-4-methyl-3-oxo pentanoic acid phenyl amide on reaction with tert-Butyl-2-[(4R, 6S)-6(amino ethyl)-2,2-dimethyl-1,3-dioxan-4-yl] acetate and fluoro benzaldehye in presence of Para toluene sulfonic acid, Isopropyl alcohol and toluene media to give Atorvastatin ester.

Stage-5

Atorvastatin ester undergoes hydrolysis in presence of sulfuric acid and methanol gives Atorvastatin.

Stage-6

Atorvastatin upon salt formation with calcium acetate in presence of Isopropyl alcohol gives Atorvastatin Calcium.



ATROVASTAIN CALCIUM

Procedure:

Stage-1

tert-Butyl-2-[(4R,6S)-6-(Cyanomethyl)-2,2-dimethyl-1,3-dioxan-4-yl]acetate

OO

OO

N + 2 H2

Hydrogen

tert-Butyl-2-[(4R,6S)-6-(aminoethyl)-2,2-dimethyl-1,3-dioxan-4yl]acetate

O O

O O

H2N

269.0 4.0

273.0

Stage-2

AnilineNH2

+

Dimethyl carbonate

O

O

O +

2-Methyl-2-butanone

CO

4-Methyl-3-oxo-N-phenyl pentanamide

O

NH

O

+ 2CH3OH

93 90 86 205 64.0



Stage-3

4-Methyl-3-oxo-N-phenyl pentanamide

O

NH

O

205

BenzaldehydeO

+

106

2-Benzylidine-4-methyl-3-oxo pentanoic acid phenylamide

O

NH

O

293

+ H2O

18 Stage-4

2-Benzylidine-4-methyl-3-oxo pentanoic acid phenylamide

O

NH

O

293

tert-Butyl-2-[(4R,6S)-6-(aminoethyl)-2,2-dimethyl-1,3-dioxan-4yl]acetate

O O

O O

H2N

273.0

+

Fluoro benzaldehyde

O

F

+

124

NH

O

N

O O

O

O

CCH3

CH3

CH3

F

+ 2 H2O

65436.0



Stage-5

NH

O

N

O O

O

O

CCH3

CH3

CH3

F654

+ 2 H2O

NH

O

N

OH OH

OH

O

F

36.0

+

558 58

O

+ C

CH3

CH3

CH3

HO

74



Stage-6

NH

O

N

OH OH

OH

O

F558

+ CH3COOCa

158

NH

O

N

*OH OH

O

O

F 2

Ca2+

+ 2 CH3COOH

Atorvastatin Calcium1154

120.0



ATROVASTAIN CALCIUM

Flow Chart:

Tert-Butyl-2-[(4R,6S)]-6-(cyanomethyl)-2,2-dimethyl-1,3-Dioxan-4-yl] acetatePalladium carbonMethanol

Stage-1 Methanol Rec

Stage-2

AnilineDimethyl Carbonate2-Methyl-2-ButanoneMethanol

Methanol Rec

Stage-3

Stage-2BenzaldehydePotassium carbonateAcetone

Acetone Rec

Stage-4

Stage-3FluorobenzaldehydeStage-1TolueneIPA

IPA Rec

Stage-5Atrovastatin EsterSulfuric AcidMethanol

Methanol Rec

Stage-6

AtrovastatinCalcium AcetateIPA Activated Carbon

IPA Rec

ATORVASTATIN CALCIUM



ATROVASTAIN CALCIUM

Material Balance:

Material Balance of Atrovastain Calcium Stage-1



in Kg Tert-Butyl-2-[(4R,6S)]-6-(cyanomethyl)-2,2-dimethyl-1,3-Dioxan-4-yl] acetate

66.40 Stage-1 64.00

Palladium carbon 1.20 Methanol Recovery 376.00 Methanol 400.00 Methanol Loss 24.00 Hydrogen 5.00 Palladium carbon Reuse 1.20 Organic Residue 3.40 Process Emission 4.00 (Hydrogen ) Total 472.60 Total 472.60




in Kg Aniline 27.20 Stage-2 52.00 Dimethyl Carbonate 27.20 Methanol Recovery 146.00 2-Methyl-2-Butanone 27.20 Methanol Loss 7.10 Sulfuric Acid 0.80 Effluent Water 330.40 Methanol 136.00 (Water-328,sulfuric Acid-

0.8,Methanol-1.6)

Water 328.00 Organic Residue 10.90 Total 546.40 Total 546.40






in Kg Stage-2 52.00 Stage-3 68.00 Benzaldehyde 27.60 Acetone Recovery 135.00 Potassium carbonate 5.00 Acetone Loss 5.00 Acetone 140.00 Toluene Recovery 207.00 Toluene 220.00 Toluene Loss 11.00 Water 680.00 Effluent Water 691.60 (Water-680,generated water-

4.6,Potassium carbonate-5, Toluene-2)

Organic Residue 7.00 Total 1124.60 Total 1124.60




in Kg Stage-3 68.00 Atrovastatin Ester 132.00 Fluorobenzaldehyde 28.80 IPA Recovery 304.00 Stage-1 64.00 IPA Loss 16.00 Toluene 520.00 Toluene Recovery 490.00 Paratoluene sulfonic acid 2.00 Toluene Loss 26.00 IPA 320.00 Effluent Water 694.40 Water 680.00 (Water-680,generated water-

8.4,PTSA-2,Toluene-4)







in Kg Atrovastatin Ester 132.00 Atrovastatin 106.40 Sulfuric Acid 2.40 Methanol Recovery 456.00 Methanol 480.00 Methanol Loss 24.00 Water 800.00 Effluent Water 821.80 (Water-792.8,Sulfuric acid-2.4,

Acetone-11.7,tert-butanol-14.9)





in Kg Atrovastatin 106.40 Atrovastatin Calcium 100.00 Calcium Acetate 15.00 IPA Recovery 380.00 IPA 400.00 IPA Loss 20.00 Activated Carbon 2.00 Acetic Acid 11.40 Spent Carbon 2.00 Organic Residue 10.00 Total 523.40 Total 523.40



4. LANSOPRAZOLE

Process Description

Stage-1

2, 3-Lutidine oxidised with Hydrogen Peroxide in the Presence of Acetic acid and

subsequently on Nitration with Nitric Acid, Sulfuric Acid to produces stage-1

Stage-2

Stage-1 Product reacts with 2, 2, 2- tri fluoro ehtanol and Sodium hydroxide to give

Stage-2A reaction mass. Reaction Mass (Stage-2A) reacts with Acetic Anhydride in

presence of Acetic Acid, an intermediate is formed. Further it is treated with dry

hydrochloric acid and Sodium hydroxide to give stage-2 Compound.

Stage-3

Above compound Chlorinated with Thionyl chloride in presence of Toluene solvent

media to give stage-3 chloro compound

Stage-4

Stage-3 Condensed with 2-Mercapto benz imidazole in Presence of Sodium Hydroxide

and Toluene solvent media to give Stage-4 Compound.

Stage-5

Stage-4 Compound reacts with Hydrogen peroxide in presence of IPA produces

pharma. The product is further purified with carbon and Water to get pure compound of

Lansoprazole.



LANSOPRAZOLE

Route of Synthesis:

Stage-1

N

CH3

CH3

2,3-Lutidine

107.00

+ H2O2

Hydrogen peroxide

34.00

+ HNO3

Nitric acid

63.00

N

NO2

CH3

CH3

O

+ 2

4-Nitro-2,3-Dimethyl pyridine-N-Oxide

168.00

Water

36.0

H2O

C7H9N C7H8N2O3

Stage-2

N

NO2

CH3

CH3

O

+

4-Nitro-2,3-Dimethyl pyridine-N-Oxide

168.00

CF3CH2OH + K2CO3 + (CH3CO)2O + NaoH + HCl

Trifluoro ethanol

Potassium carbonate

Acetic anhydride

Sodium hydroxide

Hydrogen chloride

100 138 102 40 36.5

N

OCH2CF3

CH3

CH2OH

. HCl

2-Hydroxy methyl-3-methyl pyridine hydrochloride

257.5

+ KHCO3

Potassium bicarbonate

100

+ KNO2

Potassium nitrite

85

+ CH3COONa

Sodium acetate

82

+ CH3COOH

Acetic acid

60

C7H8N2O3

C9H11ClF3NO2



Stage-3

N

OCH2CF3

CH3

CH2OH

. HCl

2-Hydroxy methyl-3-methyl pyridine hydrochloride

257.5

+ SOCl2

Thionyl chloride

119

N

OCH2CF3

CH3

CH2Cl

. HCl

2-Chloromethyl-3-methyl pyridine hydrochloride

276

+ SO2

64

+ HCl

36.5

C9H11ClF3NO2C9H10Cl2F3NO

Stage-4

N

OCH2CF3

CH3

CH2Cl

. HCl

2-Chloromethyl-3-methyl pyridine hydrochloride

276

+N

HN

HS + 2 NaoH

2-Mercapto benzimidazole

Sodium hydroxide

2x40=80.0

150

N

OCH2CF3

CH3

CH2 SN

HN

2[4-(2,2,2-Tri fluoro ethoxy)-3-methylpyridinyl]methyl thio]-1H-Benzimidazole

+ 2 NaCl

Sodium chloride

2x58.5=117.0

+ 2H2O

Water

36.0

C9H10Cl2F3NO C7H6N2S

C16H14F3N3OS

353.0



Stage-5

N

OCH2CF3

CH3

CH2 SN

HN

2[4-(2,2,2-Tri fluoro ethoxy)-3-methylpyridinyl]methyl thio]-1H-Benzimidazole

353

+ H2O2

Hydrogen peroxide

34

N

OCH2CF3

CH3

CH2 SN

HN

O

Lansoprazole

369

+ H2O

Water

18

C16H14F3N3OS

C16H14F3N3O2S



LANSOPRAZOLE

Flow Chart:

Stage-1

Stage-2

2,3-LutidineAcetic AcidHydrogen Peroxide (50%)Sulfuric AcidNitric Acid

Effluent water

Stage-1Sodium HydroxidePotassium CarbonateMIBKToluene

MIBK RecToluene Rec

Stage-3

Stage-4

Stage-5

Stage-2Methylene DichlorideTolueneThionyl Chloride

Toluene RecSulfur dioxide

Stage-3Sodium Hydroxide

Sodium chlorideEffluent water

Stage-4Isopropyl AlcoholHydrogen Peroxide (50%)ChloroformAcetoneSodium Hydroxide

Acetone RecChloroform Rec

LANSOPRAZOLE



LANSOPRAZOLE

Material Balance:

Material Balance of Lansoprazole Stage-1



in Kg 2,3-Lutidine 46.00 Stage-1 65.00 Acetic Acid 46.00 Spent Sulfuric Acid 108.00 Hydrogen Peroxide (50%) 33.00 Spent Acetic Acid for sale 46.00 Sulfuric Acid 108.00 Aqueous send to Auth. Party 358.80 Nitric Acid 30.00 (Water-322, gen.water-15.5,water

from hydrogen peroxide-16.5, Nitric acid-2.9, hydrogen peroxide-1.9)

Water 322.00 Organic Residue 7.20 Total 585.00 Total 585.00




in Kg Stage-1 65.00 Stage-2 90.00 Sodium Hydroxide 18.00 MIBK Recovery 124.00 Potassium Carbonate 53.00 MIBK Loss 6.00 Tri Fluoro Ethanol 39.00 Toluene Recovery 215.00 MIBK 130.00 Toluene Loss 10.00 Acetic Anhydride 130.00 Acetic Anhydride Recovery 87.00 TEBAC 1.00 Acetic Anhydride Loss 4.00 Toluene 225.00 Effluent Water 1429.00 Hydrogen Chloride Gas 14.00 (Water-1300, Potassium Nitrite-

33,Potassium Bicarbonate-39,Sodium Acetate-31,Sodium Hydroxide-3, Acetic Acid-23)

Activated Carbon 3.00 Organic Residue 10.00 Water 1300.00 Spent Carbon 3.00 Total 1978.00 Total 1978.00






in Kg Stage-2 90.00 Stage-3 90.00 Methylene Dichloride 175.00 Toluene Recovery 225.00 Toluene 235.00 Toluene Loss 10.00 Thionyl Chloride 41.00 Methylene Dichloride Recovery 167.00 Methylene Dichloride Loss 8.00 Organic Residue 6.00 Process Emissions 35.00 (Sulfur Dioxide-22,Hydrogen

Chloride-13)

Total 541.00 Total 541.00




in Kg Stage-3 90.00 Stage-4 105.00 Sodium Hydroxide 30.00 Effluent Water 594.00 Water 540.00 (Water-540, gen.Water-12,Sodium

Chloride-38,Sodium hydroxide-4)

2-Mercapto Benzimidazole 49.00 Organic Residue 10.00 Total 709.00 Total 709.00






in Kg Stage-4 105.00 Lansoprazole Pharma 100.00 Isopropyl Alcohol 250.00 Isopropyl Alcohol Recovery 237.50 Hydrogen Peroxide (50%) 22.00 Isopropyl Alcohol Loss 10.00 Catalyst 1.00 Chloroform Recovery 436.75 Chloroform 465.00 Chloroform Loss 23.25 Acetone 125.00 Acetone Recovery 116.75 Sodium Hydroxide 12.00 Acetone Loss 6.25 Acetic Acid 18.00 Effluent Water 424.50 Water 375.00 (Water-375,Isopropyl Alcohol-

2.5,Sodium Acetate-25,Hydrogen Peroxide-1,gen.Water-10,Water from Hydrogen Peroxide-11)

Catalyst Reuse 1.00 Organic Residue 17.00 Total 1373.00 Total 1373.00



5. SILDENAFIL CITRATE


Stage-1

4-Amino-1-methyl-3-n-propyl pyrazole-5-carboxamide reacts with 2-Ethoxy-5-(4-methyl

piperazinyl) sulfonic benzoic acid in the presence of MDC as solvent media to give

stage-1 as product.

Stage-2

Stage-1 reacts with potassium hydroxide and H ydrochloric acid in the presence of t-

Butanol as a solvent media to give stage-2 as product.

Stage-3

Stage-2 reacts with citric acid in the presence of acetone as a solvent media to give

sildenafil citrate as product.



SILDENAFIL CITRATE

Route of synthesis:

Stage-1:

2-Ethoxy-5-(4-methyl piperazinyl)sulfonyl benzoic acid

N

NS COOH

OC2H5H3C

O O

C14H20N2O5S

328.38

+

4-Amino-1-methyl-3-n-propyl pyrazole-5-carboxamide

NN

H2N

H2N

CH3

CH3

O

C8H14N4O

182.22

+ SOCl2

Thionyl chloride

118.97

+ NH3

17.03

Ammonia

N

NS

OC2H5H3C

O O

NH

NNCH3

H2N

CH3

O

O

4-[2-Ethoxy-5-(4-methyl-piperazine-1-sulfonyl)-benzoylamino]-2-methyl-5-propyl-2H-pyrazole-3-

carboxylic acid amide

C22H32N6O5S

492.59

+ SO2

Sulphur dioxide

64.06

+ HCl

Hydrochloric acid

36.5

+ NH4Cl

53.49

Ammonium chloride

MDC



Stage-2:

N

NS

OC2H5H3C

O O

NH

NNCH3

H2N

CH3

O

O

4-[2-Ethoxy-5-(4-methyl-piperazine-1-sulfonyl)-benzoylamino]-2-methyl-5-propyl-2H-pyrazole-3-

carboxylic acid amide

C22H32N6O5S

492.59

N

NS

N

HNN

N

CH3

CH3

O

OO

H3C OC2H5

5-[2-Ethoxy-5-(4-methyl-piperazine-1-sulfonyl)-phenyl]-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one

C22H30N6O4S

474.57

+ KOH + HCl

Potassium hydroxide

56.10

Hydrochloric acid

36.5

+ 2H2OKCl +

74.55

Potassium chloride 2X18=36.00

t-Butanol



Stage-3:

N

NS

N

HNN

N

CH3

CH3

O

OO

H3C OC2H5

Sildenafil Base

C22H30N6O4S

474.57

+

Citric acid

HO COOH

COOH

COOH

C6H8O7

192.12

Acetone

N

NS

N

HNN

N

CH3

CH3

O

OO

H3C OC2H5

HO COOH

COOH

COOH

Sildenafil Citrate

C28H38N6O11S

666.69



SILDENAFIL CITRATE

Flow Chart:

Stage-1

Stage-2

Stage-3

4-Amino-1-methyl-3-n-propyl pyrazole-5-carboxamide2-Ethoxy-5-(4methylpiperazinyl)sulfonyl benzoic acidThionyl chlorideDMF

DMF Rec

Stage-1Potassium hydroxideHydrochloric acid (30%)t-Butanol

t-Butanol Rec

Stage-2Citric acidAcetone

Acetone Rec

SILDENAFIL CITRATE



SILDENAFIL CITRATE

Material Balance:

Material Balance of Sildenafil Citrate Stage1

Batch Size: 100 Kg Name of the input Quantity


in Kg 4-Amino-1-methyl-3-n-propyl pyrazole-5-carboxamide

29.50 Stage-1 77.50

2-Ethoxy-5-(4methylpiperazinyl) sulfonyl benzoic acid

53.10 MDC Recovery 285.00

Thionyl chloride 19.30 MDC Loss 15.00 Ammonia 2.80 Petroleum ether Recovery 57.00 DMF 0.50 Petroleum ether Loss 3.00 MDC 300.00 Effluent Water 517.30

Sodium sulfate 20.00 (Water-500,Ammonium chloride-

8.7,DMF-0.5,Hydrochloric Acid-5.92,Organic impurities-2.18)

Petroleum ether 60.00 Inorganic Solid Waste 20.00 Water 500.00 (Sodium sulfate) Process Emission 10.40 (Sulfur dioxide) Total 985.20 Total 985.20

Material Balance of Sildenafil Citrate Stage-2



in Kg Stage-1 77.50 Stage-2 73.00 Potassium hydroxide 10.00 t-Butanol Recovery 283.00 Hydrochloric acid (30%) 21.70 t-Butanol Loss 15.00 t-Butanol 300.00 Effluent Water 386.50 Water 350.00 (Water-350,generated water-6,

Potassium chloride-13.3,t-Butanol-2,water from HCl-15.2)




Material Balance of Sildenafil Citrate Stage-3



in Kg Stage-2 73.00 Sildenafil Citrate 100.00 Citric acid 29.50 Acetone Recovery 283.00 Acetone 300.00 Acetone loss 15.00 Organic Residue 4.50 (Organic Impurities-2.5,Acetone-

2)




6. ZIDOVUDINE

Process Description

Stage-1

β-Thymidine is reacted with Trityl chloride and Tri ethyl amine in the presence of 1, 4-dioxane to give 5’-O-Trityl Thymidine.

Stage-2

5’-O-Trityl Thymidine is reacted with methane sulphonyl chloride and tri ethylamine in the presence of Toluene to give mesyl thymidine intermediate, which is reacted with tri ethylamine in the presence of methanol to give 5’-O- Trityl -2,3’-Anhydro Thymidine. Stage-3

5’-O-Trityl -2, 3’-Anhydro Thymidine is reacted with sodium azide and ammonium chloride in the presence of di methyl sulphoxide to give 5’-O-Trityl -Zidovudine.

Stage-4

5’-O-Trityl –Zidovudine is reacted with p-Toluene sulphonic acid monohydrate in the presence of Methanol to give Zidovudine.



ZIDOVUDINE

Route of Synthesis:

Stage-1

OHO

HO

N

HN

O

O

CH3

+ (C6H5)3CCl

Triethyl amine

+ C6H15N1,4-Dioxane

C O O

HO

N

HN

O

O

CH3

+

Thymidine

C10H14N2O5

242.23

Trityl chloride

278.78 101.19

Trityl thymidine

C29H28N2O5

484.54

C6H15N.HCl

Triethyl amine hydrochloride

137.69



Stage-2

Step-A

C O O

HO

N

HN

O

O

CH3

Trityl thymidine

C29H28N2O5

484.54

+ CH3SO2Cl + C6H15N

114.55 101.19

Toluene

C O O

O

N

HN

O

O

CH3

+

SO2CH3

C6H15N.HCl

Methanesulfonic acid 5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-2-trityloxymethyl-tetrahydro-furan-3-yl ester

137.69

C30H30N2O7S

562.63



Step-B

C O O

O

N

HN

O

O

CH3

SO2CH3

Methanesulfonic acid 5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-2-trityloxymethyl-tetrahydro-furan-3-yl ester

C30H30N2O7S

562.63

C O ON

N

O

CH3

O

Methanol

5-O-Trityl-2,3-anhydro thymidin

C29H26N2O4

466.53

+ C6H15N

101.19

+

C7H16O3S

Triethyl methane sulfonate

SO O

O

180.27

+ NH3

17.0



Stage-3

C O ON

N

O

CH3

O

5-O-Trityl-2,3-anhydro thymidin

C29H26N2O4

466.53

+ NaN3 + NH4Cl

C O ON

HN

O

CH3

+

O

N3

NaCl + NH3

5-O-Trityl-Zidovudine

C29H27N5O4

509.56

58.5

Sodium azide

65.01

53.49

17.0



Stage-4

C O ON

HN

O

CH3

O

N3

5-O-Trityl-Zidovudine

C29H27N5O4

509.56

++ H2O

Methanol

HO ON

HN

O

CH3

O

N3

+ C O +

Zidovudine

C10H13N5O4

267.24

Trityl methyl Ether

CH3

S OO

OH

p-Toulenesulfonic Acid

C7H8SO3

172.2

CH3

C20H18O

274.36

S OO

Sulfonic Acid

OH

C6H6O3S

158.18

18.0



ZIDOVUDINE

Flow Chart:

Stage-1

Zidovudine

Beta-Thymidine1,4-DioxaneTri ethyl amineTrityl chlorideToluene

Stage-2

TolueneMethyl sulfonyl chlorideTri ethyl amineMethanol

Sodium azideAmmonium chlorideDMSO

Stage-3

TolueneMethanolPTSA MonohydrateSodium carbonateEthyl AcetateActivated Carbon

Stage-4

1,4-Dioxane RecoveryTEA HClToluene Recovery

TEA HClMethanol RecoveryOrganic Residue

DMSO RecoveryOrganic Residue

Toluene RecoveryMethanol RecoveryEthyl Acetate RecvoerySpent Carbon



ZIDOVUDINE

Material Balance:

Material balance of Zidovudine Stage-1

Batch Size:50.0 Kg Name of the input Quantity


In Kg β-Thymidine 70.00 Stage-1 110.00 1,4-Dioxane 700.00 1,4-Dioxane Recovery 665.00 Tri ethyl amine 23.00 1,4-Dioxane Loss 35.00 Trityl chloride 64.00 Toluene Recovery 472.00 Toluene 500.00 Toluene Loss 25.00 Water 950.00 Effluent water 984.30 (Water-950,Triethyl Amine

Hydrochloride-31.3,Toluene-3)





In Kg Stage-1 110.00 Stage-2 100.00 Toluene 1200.00 Toluene Recovery 1138.00 Methyl sulfonyl chloride 26.00 Toluene Loss 60.00 Tri ethyl amine 50.00 Methanol Recovery 663.00 Methanol 700.00 Methanol Loss 35.00 Water 1000.00 Effluent water 1039.80 (Water-1000,Triethyl Amine

Hydrochloride-31.3,TEA-4.5,Toluene-2,Methanol-2)

Organic Residue 6.40 By-Product 40.00 (Tri ethyl methane sulfonate) Process Emission 3.80 (Ammonia) Total 3086.00 Total 3086.00






In Kg Stage-2 100.00 Stage-3 100.00 Sodium azide 14.00 DMSO Recovery 565.00 Ammonium chloride 12.00 DMSO Loss 30.00 DMSO 600.00 Effluent water 1417.60 Water 1400.00 (Water-1400,Sodium

Chloride-12.6,DMSO-5)

Process Emission 3.65 (Ammonia) Organic Residue 9.75 Total 2126.00 Total 2126.00




In Kg Stage-3 100.00 Zidovudine 50.00 Toluene 1920.00 Toluene Recovery 1824.00 Methanol 800.00 Toluene Loss 94.00 PTSA Monohydrate 34.00 Ethyl Acetate Recovery 1235.00 Sodium carbonate 10.00 Ethyl Acetate Loss 65.00 Ethyl Acetate 1300.00 Methanol Recovery 758.00 Activated Carbon 5.00 Methanol Loss 40.00 Water 1200.00 Effluent water 1241.70 (Water-1196.5,Sulfonic Acid-

31.2,Sodium carbonate-10,Methanol-2,Toluene-2)

Spent Carbon 5.00 By-Product 53.84 (Trityl methyl Ether) Organic Residue 2.46 Total 5369.00 Total 5369.00



7. LEVO CETIRIZINE DI HYDROCHLORIDE

Process Description

Stage-1

Step-A

P-Chlorobenzo phenone is condensed with Ammonium formate to produce the C-(4-Chloro-phenyl)-C-phenyl methylamine

Step-B

C-(4-Chloro-phenyl)-C-phenyl methylamine reacts with Hydrochloric Acid in the presence of Methanol solvent media to get Stage-1 Compound.

Stage-2

Stage-1 reacts with Sodium hydroxide in the presence of L-tartaric acid to get Stage-2 compound.

Stage-3

Stage-2 is treated with p- Toluene sulphonyl chloride and Sodium hydroxide in Methylene dichloride medium, the compound is obtained

Stage-4

Stage-2 and Stage-3 Compound on condensation in Methanol medium, the product is obtained.

Stage-5

Stage-4 is treated with Hydrobromic Acid and Dilute Acetic acid, the compound is obtained

Stage-6

Stage-5 reacts with Chloro ethanol in the presence of Triethyl amine to get stage-6 Compound

Stage-7

Stage-6 is treated with Sodium monochloro acetate in the presence of Hydrochloric acid and DMF solvent media to get Levocetrizine dihydrochloride



LEVO CETRIZINE DI HYDROCHLORIDE

Route of Synthesis:

Stage-1

Step-A

O

Cl

p-chloro benzophenone

C13H9ClO216.66

Ammonium formate

63.05

+ Toluene

Cl

NH2

C-(4-Chloro-phenyl)-C-phenyl-methylamine

C13H12ClN217.69

+ CO2 + H2O

Carbon dioxide

44

Water

18

NH4HCO2

Step-B

Cl

NH2 +


C13H12ClN217.69

HCl

Hydrochloric acid

36.5

Methanol

Cl

NH2


C13H13Cl2N254.19

HCl



Stage-2

Cl

NH2


C13H13Cl2N254.19x2=508.38

HCl

2 + 2NaOHL-Tataric acid

Water

Cl

NH2

Cl

NH2+

Sodium hydroxide

2x40=80



+ 2 NaCl

C13H12ClN217.69

C13H12ClN217.69

+ 2 H2O

Sodium chloride

2x58.5=117

Water

2x18=36

(+d) (-l)

Stage-3

para toluene sulphonyl chloride

C7H7ClO2S 190.65

n,n-bis( 2-chloro ethyl) amine Hydrochloride

C4H10Cl3N 178.5

SodiumHydroxide

2X40=80

1-Methanesulfonyl-4-methyl-benzene,(2-chloro-ethyl)-chloromethyl-amine

CH3

SO2Cl

+ HN

Cl

ClHCl

+ 2NaOHMDC

CH3

SO2 N

Cl

Cl

C11H15Cl2NO2S

296.21

+ 2NaCl

Sodium chloride

2x58.5=117

+ 2H2O

36.0



Stage-4

1-Methanesulfonyl-4-methyl-benzene,(2-chloro-ethyl)-chloromethyl-amine

CH3

SO2 N

Cl

Cl

C11H15Cl2NO2S

296.21

Cl

NH2

+

(L)_(4-Chloro-phenyl)-C-phenyl-methylamine-1-methane sulfonyl-4-methyl-benzene(2-ethyl-methyl-amine

C13H12ClN

217.69

N

Cl

N S

O

O

CH3

1-[(4-Chloro-phenyl)-phenyl-methyl]-4-(toluene-4-sulfonyl)-piperazine

+

C24H25ClN2O2S

440.50

MeOH

2HCl

Hydrochoric acid

2x58.5=117.0



Stage-5

N

Cl

N S

O

O

CH3

1-[(4-Chloro-phenyl)-phenyl-methyl]-4-(toluene-4-sulfonyl)-piperazine

C24H25ClN2O2S

440.99

+ HBr + CH3COOH

Hydrobromic acid

81.0

Acetic acid

60.0

+ H2O

Water

18.0

N

HN

Cl1-[(4-Chloro-phenyl)-phenyl-methyl]-piperazine

+ CH3COOBr +

SO2H

CH3

C17H19ClN2

286.80

Bromo acetate

138.95

pTSA

156.20

C7H8O2S



Stage-6

N

HN

Cl

1-[(4-Chloro-phenyl)-phenyl-methyl]-piperazine

C17H19ClN2

286.80

+

Chloro ethanol

C2H5ClO

80.51C19H23ClN2O

330.85

CH3

OH

Cl

1-{4-[(4-Chloro-phenyl)-phenyl-methyl]-piperazin-1-yl}-ethanol

CH3

NN

Cl

OH

TEA+ HCl

36.5

Stage-7: Pharma

C19H23ClN2O

330.85

1-{4-[(4-Chloro-phenyl)-phenyl-methyl]-piperazin-1-yl}-ethanol

CH3

NN

Cl

OH

Sodium monochloro acetate

Na+

O

O-Cl + 2HCl

DMF

C2H2ClNaO2

116.48

Hydrochloric acid

2x36.5=73

NaCl

Levocetrizine dihydrochloride Sodium chloride

58.50C21H25ClN2O3.2HCl

461.89

+

CH3

O

OO

N

N

Cl2 HCl

+



LEVOCETRIZINE DIHYDROCHLORIDE

Flow Chart:

Stage - 1

Stage - 2

Stage - 3

Stage - 4

Stage - 5

p-chloro benzo phenoneAmmonium formateHydrochloric acidToluene

Generated waterCarbon dioxideToluene Recovery

Stage-1Sodium hydroxideTartaric acidMDC

Sodium chlorideGenerated waterMDC Recovery

para toluene sulphonylchloriden,n-bis( 2-chloro ethyl)amine HClSodium HydroxideMDC

Sodium chlorideGenerated waterMDC Recovery

Stage-3Stage-2Ethyl di isopropyl amineMethanol

Hydrochloric acidMethanol Recovery

Stage-4Hydrobromic acidAcetic acidToluene

Bromo acetatePTSAToluene Recovery

Stage - 6Stage-5Chloro ethanolTriethylamineToluene

TEA HydrochlorideToluene Recovery

Stage - 7

Stage-6Sodium mono chloro acetateHydrochloric acidDMFAcetone

Sodium chlorideAcetone Recovery

LevocetirizineDi Hydrochloride



LEVO CETRIZINE DI HYDROCHLORIDE

Material Balance:

Material balance of Levo Cetrizine di Hydrochloride Stage-1


in kg Name of the out put Quantity

in Kg p-chloro benzo phenone 120.00 Stage-1 140.00 Ammonium formate 35.00 Toluene Recovery 760.00 Hydrochloric acid 25.00 Toluene Loss 40.00 Toluene 800.00 Effluent Water 915.50 Activated carbon 10.00 (Water-900,generated water-

10,Hydrochloric acid-5, Toluene-0.5)

Water 900.00 Spent carbon 10.00 Process Emission 24.50 (Carbon dioxide) Total 1890.00 Total 1890.00




in Kg Stage-1 140.00 L-Stage-2 60.00 Sodium hydroxide 25.00 MDC Recovery 665.00 Tartaric acid 32.00 MDC Loss 35.00 MDC 700.00 Effluent Water 877.00 Water 800.00 (Water-800, generated water-

10,Sodium Chloride-32, Sodium hydroxide-3, L-Tartaric Acid-32)

D-Isomer Recycle 60.00 Total 1697.00 Total 1697.00






in Kg para toluene sulphonyl chloride 52.00 Stage-3 80.00 n,n-bis( 2-chloro ethyl)amine HCl

50.00 MDC Recovery 665.00

Sodium Hydroxide 25.00 MDC Loss 35.00 MDC 700.00 Effluent Water 844.88 Water 800.00 (Water-800,generated water-

9.8,Sodium chloride-31.9,Sodium hydroxide-3.18)





in Kg Stage-3 80.00 Stage-4 110.00 Stage-2 60.00 Methanol Recovery 380.00 Ethyl di isopropyl amine 28.00 Methanol Loss 20.00 Methanol 400.00 Spent Hydrochloric Acid 19.70 Ethy ldi isopropyl amine Reuse 28.00 Organic Residue 10.30 Total 568.00 Total 568.00






in Kg Stage-4 110.00 Stage-5 70.00 Hydro bromic acid 23.00 Toluene Recovery 372.00 Acetic acid 15.00 Toluene Loss 20.00 Toluene 400.00 Effluent Water 576.91

Water 500.00

(Water-500,Bromoacetate-34.65,Hydrobromic Acid-2.8, PTSA-38.96,Toluene-0.5)

Organic Residue 9.09

(Organic Impurities-7.59,

Toluene-1.5) Total 1048.00 Total 1048.00

Material balance of Levo Cetrizine di-Hydrochloride Stage-6



in Kg Stage-5 70.00 Stage-6 75.00 Chloro ethanol 20.00 Toluene Recovery 373.00 Triethyl amine 24.70 Toluene Loss 20.00 Toluene 400.00 Effluent Water 388.95

Water 350.00

(Water-350,Triethyl amine hydrochloride-36.6,Chloro ethanol-0.35,Toluene-2)




Material balance of Levo Cetrizine di-Hydrochloride Stage-7:Pharma



in Kg Stage-6 75.00 Levo Cetrizine di-Hydrochloride 100.00 Sodium mono chloro acetate 27.00 MDC Recovery 238.00 Hydrochloric acid 17.00 MDC Loss 12.00 Di methyl formamide 100.00 Acetone Recovery 89.00 MDC 250.00 Acetone Loss 5.00 Activated Carbon 10.00 DMF Recovery 89.00 Acetone 100.00 DMF Loss 5.00 Water 200.00 Effluent Water 214.26 (Water-200,Sodium chloride-

13.26,Acetone-0.5,DMF-0.5)

Spent Carbon 10.00 Organic Residue 16.74 (Organic Impurities-15.74,

Acetone-0.5,DMF-0.5)




8. ESCITALOPRAM OXALATE

Process Description

Stage-1

4-[4-Dimethylamino-1-(4-fluoro-phenyl)-1-hydroxy-butyl]-3-hydroxy methyl-benzonitrile

Hydro bromide reacts with D-P-Toluyl-D-Tartaric Acid in the presence of Sodium

hydroxide to get DPTAA Salt (stage-1)

Stage-2

DPTAA Salt on reaction with Methane sulfonyl chloride, Triethyl amine and using

Isopropyl alcohol and Toluene as solvents forms Escitalopram Base. Escitalopram Base

on reaction with Oxalic acid using Acetone as solvent to get Escitalopram Oxalate.




Route of Synthesis:

Stage-1

Step-A

N CH3H3C

OHOH

CN

F

H3C

O

O

OHO

O

HO O

O

CH3

+

4-[(1S)-4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl) benzonitrile

Hydrobromide

D(+) Dipara Tolyl Tartaric Acid

423.32

1/2 X386.35=193.17C20H23FN2O2 HBr

C20H18O8

N CH3H3C

OHOH

CN

F

CH3

O O

OH

O

O

HO

O O

CH3

DPTTA Salt (Stage-1)

535.58

C30H32FN2O6

+ NaOH

HBr

Sodium hydroxide

40.0

1/2 + NaBr + H2O

Sodium Bromide

102.89

Water

18.0

1/2



Step-B

N CH3H3C

OHOH

CN

F

CH3

O O

OH

O

O

HO

O O

CH3

DPTTA Salt (Stage-1A)

535.58

C30H32FN2O6

1/2 + NaOH

Sodioum Hydroxide

40.0

N CH3H3C

OHOH

CN

F

CH3

O O

ONa

O

O

NaO

O O

CH3

1/2+ + H2O

Stage-1 Compound

C20H23FN2O2

342.4

D-P-Toluyl-D-Sodium Tartarate

C20H16Na2O8

1/2 X 430.32=215.16

Water

18.0



Stage-2

N CH3H3C

OHOH

CN

F

Stage-1 Compound

C20H23FN2O2

342.4

+ CH3SO2Cl + (C2H5)3N +

Oxalic Acid dihydrate

O

OHO

HO

2 H2O

MSC TEA

114.55 101.19 C6H6O6

126.0

O

F

N

CH3

CH3

CN

O

OHO

HO

Escitalopram Oxalate

C22H23FN2O5

414.43

+ CH3SO3H + (C2H5)3N HCl + 2H2O

MSA TEA HCl Water

96.11 137.65 36.0




Flow Chart:

4-[4-Dimethylamino-1-(4-fluoro-phenyl)-1-hydroxy-butyl]-3-hydroxy methyl-benzonitrile HBrD-P-Toluyl-D-Tartaric AcidSodium hydroxide Toluene

Stage-1Methane Sulfonyl ChlorideTriethyl amineMDCSodium hydroxide Oxalic Acid

Stage-1

Stage-2 Methane sulfonic acidMDC Rec

Sodium bromideToluene Rec





Material Balance:

Material Balance of Escitalopram oxalate Stage-1



in Kg 4-[4-Dimethylamino-1-(4-fluoro-phenyl)-1-hydroxy-butyl]-3-hydroxy methyl-benzonitrile HBr

120.00 Stage-1 85.00

D-P-Toluyl-D-Tartaric Acid 48.00 Toluene Recovery 662.00 Sodium hydroxide (20%) 100.00 Toluene Loss 35.00 Toluene 700.00 Isopropyl Alcohol Recovery 475.00 Isopropyl Alcohol 500.00 Isopropyl Alcohol Loss 25.00 Water 800.00 Effluent Water 916.63 (Water-800,generated water-9.63,

Sodium bromide-25.5,water from sodium hydroxide-80,Toluene-1.5)

D-P-Toluyl-D-Sodium Tartarate unreacted

53.40

Organic Residue 15.97 (Organic Impurities-14.47,

Toluene-1.5)

Total 2268.00 Total 2268.00



Material Balance of Escitalopram oxalate Stage-2



In Kg Stage-1 85.00 Escitalopram Oxalate 100.00 Methane Sulfonyl Chloride 28.50 MDC Recovery 1140.00 Triethyl amine 25.00 MDC Loss 60.00 MDC 1200.00 Acetone Recovery 428.00 Sodium hydroxide (10%) 100.00 Acetone Loss 22.00 Oxalic Acid 32.00 Effluent Water 917.01 Acetone 450.00 (Water-750,generated water-8.94,

MSA-23.9,TEA HCl-34.17, Sodium Hydroxide-10,water from sodium hydroxide-90)

Activated Carbon 10.00 Spent Carbon 10.00 Water 750.00 Organic Residue 3.49 Total 2680.50 Total 2680.50



9. LAMIVUDINE


Stage-1: Menthol condensed with Glyoxalic acid, Formaldehyde in presence of cyclohexane

solvent to give Stage-1 Compound

Stage-2 Stage-1 Compound reacts with [1, 4] Dithane-2,5-diol in presence of Triethyl amine,

Acetic Acid and Toluene solvent media to give stage-2 product. Further it is

recrystallized in n-Hexane to give pure compound of Stage-2.

Stage-3: Stage-2 Compound chlorinated with Thionyl chloride and condensed with cytosine to

produce Lamivudine crude compound in presence of Toluene and MDC solvents media.

Further Compound is purified in Activated Carbon, Water and MDC to give Pure

Compound of Lamivudine



LAMIVUDINE

Route of Synthesis:

Stage-1

H3CCH3

CH3

OH

Menthol

C10H20OMol. Wt.: 156.3

+ O

O

OH

Glyoxalic acid

C2H2O3Mol. Wt.: 74.0

Cyclohexane O

O

CH3

H3C CH3

O

+ H2O

Stage-1C12H20O3

Mol. Wt.: 212.3

Water

Mol.wt:18

Stage-2

O

O

CH3

H3C CH3

O

Stage-1C12H20O3

Mol. Wt.: 212.3

S

S OH

HO

[1,4]Dithiane-2,5-diol

C4H8O2S2Mol. Wt.: 152.2

+2 Toluene

N-Hexane

CH3

H3C CH3

OS

OH

2

Stage-2

C14H24O4SMol. Wt.: 288.4

COOH



Stage-3

CH3

H3C CH3

OS

OH

COOH

Stage-2C14H24O4S

Mol. Wt.: 288.4

+ SOCl2

Thionyl chloride

Mol.Wt:119

MDC

CH3

H3C CH3

OS

OH

COCl+ SO2 + HCl

Stage-3A SulphurDioxide

HydrochloricAcid

64 36.5Mol.Wt:306.5

CH3

H3C CH3

OS

OH

COCl

Stage-3A

Mol.Wt:306.5

N

ONH

H2N

cytosine

C4H5N3OMol. Wt.: 111.1

+Toluene N

ONH

N

CH3

H3C CH3

OS

OH

O

+ HCl

HydrochloricAcid

36.5

Lamivudine

C18H27O4N3SMol. Wt.: 381.6

C14H23O3SCl

C14H23O3SCl



LAMIVUDINE

Flow Chart:

Stage-1

Stage-2

Stage-3

L(+ )MentholGlyoxalic Acid (35%)Sodium BisulfateSodium CarbonateFormaldehydeCyclohexane

Cyclohexane Rec

Stage-12,5 DiethaneAcetic AcidTriethyl AmineToluene

Toluene Rec

Stage-2CytosineHMDSThioinyl ChlorideDimethylformamide

DMF Rec

LAMIVUDINE



LAMIVUDINE

Material Balance:

Material Balance of Lamivudine Stage-1



in Kg L(+ )Menthol 82.60 Stage-1 112.00 Glyoxalic Acid (35%) 112.00 Cyclohexane Recovery 1055.00 Sodium Bisulfate 63.00 Cyclohexane Loss 45.00 Sodium Carbonate 15.00 Effluent Water 2416.60 Formaldehyde 16.00 (Water-2300,gen.water-9.8,water

From Glyoxalic Acid-72.8,Sodium Carbonate-15,Sulphuric Acid-3,Formaldehyde-16)

Sulphuric Acid 3.00 Inorganic Solid Waste 63.00 Cyclohexane 1100.00 (Sodium Bisulfate) DM Water 2300.00 Total 3691.60 Total 3691.60




in Kg Stage-1 112.00 Stage-2 152.00 2,5 Diethane 80.00 Toluene Recovery 665.00 Acetic Acid 43.00 Toluene Loss 35.00 Triethyl Amine 3.00 n-Hexane Recovery 220.00 Toluene 700.00 n-Hexane Loss

10.00 n-Hexane 230.00 Effluent Water 2046.00 Activated Carbon 5.00 (Water-2000,Acetic Acid-

43,Triethyl Amine-3)

DM Water 2000.00 Spent Carbon 10.00 Hyflo 5.00 By-Product 40.00 (Thioacetic Acid) Total 3178.00 Total 3178.00






in Kg Stage-2 152.00 Lamivudine 200.00 Cytosine 58.55 Methylene Dichloride Recovery 1050.00 HMDS 15.00 Methylene Loss 50.00 Thioinyl Chloride 63.00 Toluene Recovery 300.00 Dimethylformamide 54.00 Toluene Loss 10.00

Triethyl amine 102.00 n-Hexane Recovery 190.00 MSA 1.00 n-Hexane Loss 10.00 Methylene Dichloride 1100.00 Ethyl Acetate Recovery 140.00 Toluene 310.00 Ethyl Acetate Loss 10.00 n-Hexane 200.00 DMF Recovery 40.00 Ethyl Acetate 150.00 DMF Loss 10.00 Water 2500.00 Triethyl Amine Reuse 102.00 HMDS Reuse 15.00 Effluent Water 2542.52 (Water-2500,Hydrochloric acid-

38.52,DMF-4)

Process Emission 33.88 (Sulphur dioxide) Organic Residue 2.15 Total 4705.55 Total 4705.55



10. LOSARTAN POTASSIUM

Process Description

Stage-1

OTBN and Sodium nitrate are made to react together in Toluene solvent medium using

TEA HCl as catalyst. Product is isolated by using Hydrochloric acid. Reaction proceeds

as per the below equation.

Stage-2

The Above stage-1 material is treated with Trityl chloride. Methylene dichloride is used

as solvent. Product is washed with water and crystallized in Methanol

Stage-3

Stage-2 is dissolved in Methylenedichloride and treated with N-Bromosuccinimide

(NBS). Methylene dichloride is distilled-off to obtain the product. Finally the product is

treated with Sodium Metabisulhite solution. The product is washed with Ethyl acetate

while centrifuging.

Stage-4

Stage-3 mass is dissolved in sodiumborohidride solution. Butylchloroformyl imidazole

(BCFI), TBAB is made to react with stage-3 solution.

Finally treated the mass is dissolved in IPA and HCL mixture. The mass is isolated by

precipitated with water. The reaction mass pH is adjusted with NaOH to get the

Losartan Base.

Stage-5

The stage-4 mass is treated with Potassium hydroxide in Methanol solvent medium.

Product is purified with Carbon. Pharma is isolated by distilling of Methanol.



LOSARTAN POTASSIUM

Route of Synthesis: Stage-1

Ortho tolylbenzonitrile

CN

CH3

+

Sodium Azide

NaN3 + NaNO2 + 2 HCl

CH3

N N

NHN

5-(4'-Methyl-biphenyl-2-yl)-2H-tetrazole

Sodium nitrite Hydrochloric Acid

C14H11N

193.24

65.0 69.0 2X36.46=72.92 C14H12N4

236.27

+ 2 NaCl + H2O + N2

2X58.44=116.89 18.0 28.0 Stage-2

CH3

N N

NHN

5-(4'-Methyl-biphenyl-2-yl)-2H-tetrazole

C14H12N4

236.27

+

trityl chloride

Cl + HCl

5-(4'-Methyl-biphenyl-2-yl)-2-trityl-2H-tetrazole

36.46

CH3

N N

NN

C19H15Cl

278.78

C33H26N4

478.59



Stage-3

5-(4'-Methyl-biphenyl-2-yl)-2-trityl-2H-tetrazole

CH3

N N

NN

C33H26N4478.59

+

N-Bromosuccinimide

OO N

Br

CH2Br

N N

NN

5-(4'-Bromomethyl-biphenyl-2-yl)-2-trityl-2H-tetrazole

C4H4BrNO2177.98

C33H25BrN4 557.48

OOHN

+

Succinimide

C4H5NO299.09



Stage-4

CH2Br

N N

NN

5-(4'-Bromomethyl-biphenyl-2-yl)-2-trityl-2H-tetrazole

C33H25BrN4 557.48

NH

N

ClCH3

HO+

HO

N

NHN

N N

N

Cl

+ NaOH

Sodium hydroxide

+

trityl alcohol

OH

Losartan Base

+ NaBr

Sodium bromide

C22H23ClN6O 422.91

C19H16O260.33

102.89

40.0C8H13ClN2O

188.65

Butylchloroformyl imidazole



Stage-5

HO

N

NHN

N N

N

Cl

Losartan Base

C22H23ClN6O 422.91

+ KOH

HO

N

NKN

N N

N

Cl

C22H22ClKN6O 461.00

Losartan PotassiumPotassium hydroxide

56.11

+ H2O

18.0



LOSARTAN POTASSIUM

Flow Chart:

Stage-1

Stage-2

Stage-3

2-Cyano-4-Methyl biphenyl Sodium AzideTEA HClSodium nitriteToluene

Toluene Rec

Stage-1Trityl chlorideTEAMDCMethanol

MDC RecMethanol Rec

Stage-2N-Bromosuccinimide Sodium meta bisulphateMethylenedichloride

MDC Rec

LOSARTAN POTASSIUM

Stage-4

Stage-3Butyl chloroformyl imidazoleTBABMethanol

Methanol Rec

Stage-5 Methanol RecStage-4Potassium hydroxideMethanolActivated Carbon



LOSARTAN POTASSIUM

Material Balance:

Material Balance Of Losartan Potassium Stage-1

Batch Size:100kg Name of the input Quantity


in Kg 2-Cyano-4-Methyl biphenyl (OTBN)

60.00 Stage-1 70.00

Sodium Azide 22.00 Toluene Recovery 377.00 TEA HCl 25.00 Toluene Loss 20.00 Hydrochloric acid 23.00 Effluent water 1068.88 Sodium nitrite 23.00 (Water-1000,generated

water-5.6,Sodium chloride-36.28,Toluene-2.0,TEA HCl-25)

Toluene 400.00 Organic Residue 8.43 Water 1000.00 (Organic Impurities-7.43,

Toluene-1)

Process Emission 8.69 (Nitrogen) Total 1553.00 Total 1553.00




in Kg Stage-1 70.00 Stage-2 120.00 Trityl chloride 83.00 MDC Recovery 380.00 TEA 30.00 MDC Loss 20.00 MDC 400.00 Methanol Recovery 90.00 Methanol 100.00 Methanol Loss 5.00 Water 300.00 Effluent Water 343.30 (Water-300,TEA HCl-40.8,

Methanol-2.5)


Methanol-2.5)







in Kg Stage-2 120.00 Stage-3 130.00 N-Bromosuccinimide (NBS) 45.00 MDC Recovery 380.00 Sodium meta bisulphate 10.00 MDC Loss 20.00 Methylenedichloride 400.00 Ethyl Acetate Recovery 190.00 Ethyl Acetate 200.00 Ethyl Acetate Loss 10.00 Water 600.00 Effluent Water 635.00 (Water-600,Sodium meta

bisulphate-10,Succinimide-25)





in Kg Stage-3 130.00 Stage-4 95.00 Butyl chloro formyl imidazole (BCFI)

45.00 Methanol Recovery 752.00

TBAB 5.00 Methanol Loss 30.00 Methanol 800.00 IPA Recovery 268.00 IPA HCl 300.00 IPA Loss 15.00 Sodium hydroxide 27.00 Effluent Water 759.70 Water 700.00 (Water-700,Sodium

bromide-24,Sodium chloride-24.8,generated water-7.4, Methanol-1.5,IPA-2)


Methanol-1.5)

By-Product 60.70 (trityl alcohol) Total 1990.00 Total 1990.00



Material Balance Of Losartan Potassium

Stage-5:Pharma Batch Size:100kg

Name of the input Quantity in Kg

Name of the out put Quantity in Kg

Stage-4 95.00 Losartan Potassium 100.00 Potassium hydroxide 20.00 Methanol Recovery 378.00 Methanol 400.00 Methanol Loss 20.00 Activated Carbon 15.00 Effluent Water 413.40 Water 400.00 (Water-400,generated water-

4,Potassium hydroxide-7.4,Methanol-2)

Spent Carbon 15.00 Organic Residue 3.60 Total 930.00 Total 930.00



WATER REQUIREMENT DETAILS

S. No Purpose Water Requirement In KLD

1 Process 43.06 2 Washings 3.00 3 Boiler Make up 47.00 4 Cooling towers Make up 24.00 5 DM Plant 2.00 6 Scrubbing system 2.00 7 Domestic 2.50 8 Gardening 5.00

Total 128.56



WASTE WATER DETAILS

S. No Purpose Effluent In KLD

1 Process 45.33 2 Washings 3.00 3 Boiler Blow down 7.00 4 Cooling Towers Blow down 4.00 5 DM Plant 2.00 6 Scrubbing system 2.00 7 Domestic 2.00

Total 65.33



HTDS & LTDS DETAILS

S. No Purpose HTDS In KLD

LTDS In KLD

Effluent In KLD

Disposal Method

1 Process 45.33 0.00 45.33 HTDS Effluent sent to ETP with MEE system. LTDS effluents treated in ETP-RO Rejects to ME system and RO permeate to reuse, Condensate from MEE to reuse and MEE residue to AFTD.

2 Washings 0.00 3.00 3.00 3 Boiler Blow down 7.00 0.00 7.00 4 Cooling towers Blow

down 0.00 4.00 4.00

5 DM Plant 2.00 0.00 2.00 6 Scrubbing system 2.00 0.00 2.00

7 Domestic 0.00 2.00 2.00 Septic tank followed by Soak pit

Total 56.33 9.00 65.33



FLOW CHART FOR EFFLUENT TREATMENT

Effluent Type

Treatment Flow

HTDS/HCOD Collection Equalization & neutralization Stripper MEE ATFD TSDF MEE Condensate will be Reused.

HTDS Collection Equalization & neutralization MEE ATFD TSDF MEE Condensate will be Reused.

LTDS/LCOD Collection ETP(Biological Treatment) Sand Filter Carbon Filter Booster pump to Membrane Filter set RO Plant RO Reject to MEE RO Permeate to Reused.



SOLID WASTE DETAILS

S. No Name of the Solid Waste Quantity In

Kg/Day

Disposal Method

1 Organic solid waste 506.00 Sent to Cement Industries 2 Inorganic solid waste 56.00 Sent to TSDF 3 Spent carbon 96.00 Sent to Cement Industries 4 Evaporation salts 2037.00 Sent to TSDF 5 Boiler ash 11750.00 Sent to Brick Manufacturers 6 ETP Sludge 50.00 Sent to TSDF 7 Spent solvents 31601.97 Recovery & Reuse



HAZARDOUS WASTE DETAILS

S. No Description Quantity Mode of Disposal

1 Waste Oils & Grease 1.2KL/Annum APPCB Authorized Agencies for Reprocessing/Recycling

2 Detoxified Containers 20 No’s/Day After Detoxification sent back to suppliers/APPCB Authorized Parties

3 Used Lead Acid Batteries 4 No’s/ Annum Send back to suppliers for buyback of New Batteries



STACK EMISSIONS FOR BOILER

Particulars Units 4.0 TPH Coal fired Boiler

Type of Fuel -- Indian Coal

Coal Consumption TPD 10.0

Ash Content % 47

Sulphur Content % 0.8

Nitrogen Content % 1.07

No. of Stacks No 1

Height of the Stack m 32

Diameter of Stack M 0.60

Temperature of Flue Gas oC 110

Velocity of Flue Gas m/s 8.5

Particulate Matter at outlet of Bag filter

(Based on 115 mg/Nm3 at outlet)

gm/sec 0.27

Sulphur dioxide emission gm/sec 1.15

Oxides of Nitrogen emission gm/sec 1.54



STACK EMISSIONS FOR DG SETS

Capacity

In KVA

Emission

of SPM in

Mg/Nm3

Emission

Of SO2 in

Mg/Nm3

Emission of NOx

in

Mg/Nm3

Stack

dia.

In m

Flue Gas

Temp. in OC

Stack

Height

in (m)

Flue gas

Velocity

In m/sec.

250 KVA

65.0 110.0 135.0 0.30 220 10 18.50



PROCESS EMISSION DETAILS

S. No Name of the Gas Quantity In Kg/Day

Treatment Method

1 Sulfur dioxide 190.00 Scrubbed by using C.S.Lye solution 2 Hydrogen 2.67 Diffused with Flame Arrestor 3 Hydrogen chloride 13.00 Scrubbed by using Water media 4 Ammonia 4.97 Scrubbed by using Chilled water

media 5 Nitrogen 8.69 Dispersed into Atmosphere



LIST OF SPENT SOLVENTS

S.No Name of the product Name of the solvent Solvent Recovery

In Kg/Batch

Solvent Recovery In Kg/day

1 Metformin Hydrochloride Xylene 1500.00 10000.00 Methanol 410.00 2733.33 2 5-Cyano Phthalide Toluene 949.00 3163.33 3 Atrovastatin Calcium Methanol 978.00 652.00 Acetone 135.00 90.00 Toluene 697.00 464.67 IPA 684.00 456.00 4 Lansoprazole MIBK 124.00 124.00 Toluene 440.00 440.00 Acetic Anhydride 87.00 87.00 Methylene Dichloride 167.00 167.00 Isopropyl Alcohol 237.50 237.50 Chloroform 436.75 436.75 Acetone 116.75 116.75 5 Sildenafil Citrate MDC 285.00 190.00 Petroleum ether 57.00 38.00 t-Butanol 283.00 188.67 Acetone 283.00 188.67 6 Zidovudine 1,4-Dioxane 665.00 443.33 Toluene 3434.00 2289.33 Methanol 1421.00 947.33 DMSO 565.00 376.67 Ethyl Acetate 1235.00 823.33 7 Levo Cetrizine di-

Hydrochloride Toluene 1505.00

1003.33 MDC 1568.00 1045.33 Methanol 380.00 253.33 Acetone 89.00 59.33 DMF 89.00 59.33 8 Escitalopram Oxalate Toluene 662.00 441.33 Isopropyl Alcohol 475.00 316.67 MDC 1140.00 760.00 Acetone 428.00 285.33 9 Lamivudine Cyclohexane 1055.00 703.33 Toluene 965.00 643.33 n-Hexane 410.00 273.33 Methylene Dichloride 1050.00 700.00



Ethyl Acetate 140.00 93.33 DMF 40.00 26.67 10 Losartan Potassium Toluene 377.00 377.00 MDC 760.00 760.00 Methanol 1220.00 1220.00 Ethyl Acetate 190.00 190.00 IPA 268.00 268.00 Total 28001.00 31601.97



PRE FEASIBILITY REPORT 1. Executive Summary NA

2. Introduction of the project/ Background information. -

(i) Identification of project and project proponent. In case

of mining project, a copy of mining Lease/ letter of intent should be given.

NA

(ii) Brief description of nature of the project. Bulk Drug & Intermediates manufacturing

(iii) Need for the project and its importance to the country and or region

Enclosed

(iv) Demand-Supply Gap.

-

(v) Imports vs. Indigenous production.

-

(vi) Export Possibility. Yes

(vii) Domestic / export Markets.

Yes

(viii) Employment Generation (Direct and Indirect) due to the project.

DIRECT- 35 INDIRECT-20

3. Project Description

(i) Type of project including interlinked and interdependent projects, if any

Bulk Drug & Intermediates manufacturing

(ii) Location (map showing general location, specific location, and project boundary & Project site layout) with coordinates.

Enclosed

(iii) Details of alternate sites considered and the basis of selecting the proposed site, particularly the environmental considerations Gone into should be highlighted.

--

(iv) Size or magnitude of operation.

Small Scale Industry(SSI)

(v) Project description with process details (a schematic diagram/ flow chart showing the Project layout, components of the project etc. should be given)

Enclosed

(vi) Raw material required along with estimated quantity, likely source, marketing area of final product/ s, Mode of transport of raw Material And Finished Product.

Enclosed

(vii) Resource optimization/ recycling and reuse envisaged in the project, if any, should be Briefly outlined.

NA

(viii) Availability of water its source, Energy/ power Requirement and source should be given.

Bore well water and water tankers



(ix) Quantity of wastes to be generated (liquid and

solid) and scheme for their Management /disposal.

---

(x) Schematic representations of the feasibility Drawing which give information of EIA purpose.

NA

4. Site Analysis

(i) Connectivity. National High way No:202 Warangal - Hyderabad

(ii) Land Form, Land use and Land ownership.

Dry Land

(iii) Topography (along with map).

Yes

(iv) Existing land use pattern (agriculture, non-agriculture, forest, water bodies (including area under CRZ) ), shortest distances from the periphery of the project to periphery of the forests, national park, wild life sanctuary, eco sensitive areas, water bodies (distance from the HFL of the river), CRZ. In case of notified industrial area, a copy of the Gazette Notification should be given.

Dry Land

(v) Existing Infrastructure. Private Land (vi) Soil classification Mixed Soil (vii) Climatic data form secondary sources. Will be submitted in EIA Report

(viii) Social Infrastructure available.

--

5. Planning Brief

(i) Planning Concept (type of industries, facilities, transportation etc) Town and Country Planning / Development authority Classification

NA

(ii) Population Projection

(iii) Land use planning (breakup along with green belt etc).

(iv) Assessment of Infrastructure Demand (Physical & Social).

(v) Amenities /Facilities.

6. Proposed Infrastructure

(i) Industrial Area (Processing Area).

--

(ii) Residential Area (Non Processing Area). ---



(iii) Green Belt.

17864.94 SQM

(iv) Social Infrastructure.

---

(v) Connectivity (Traffic and Transportation Road/Rail/ Metro/ Water ways etc)

National High way (NH-202) Hyderabad - Mumbai

(vi) Drinking Water Management (Source & Supply of water)

Potable water

(vii) Sewerage System.

Septic tank flowed by soak pit

(viii) Industrial Waste Management.

MEE System in Plant

(ix) Solid Waste Management. TSDF, Dundigal village, Quthbullapur (M), Rangareddy (Dt.)

(x) Power Requirement & Supply / source.

850 H.P, APSPDCL

7. Rehabilitation and Resettlement (R & R) Plan

(i) Policy to be adopted (Central/ State) in respect of the project affected persons including home oustees, land oustees and landless laborers (a brief outline to be given)

NA

8. Project Schedule & Cost Estimates (i) Likely date of start of construction and likely

date of completion ( Time schedule for the Project to be given).

-----

(ii) Estimated project cost along with analysis in terms of economic viability of the project.

12.98 Crores

9. Analysis of proposal (Final Recommendations)

(i) Financial and social benefits with special emphasis on the benefit to the local people Including tribal population, if any, in the area.

These types of industries will contribute in development of local villagers because of employment to the locals.



Proposed Draft Terms of Reference for Preparation of EIA & EMP For M/s. S. M. Labs (P) Ltd., Unit - III

1 Executive summary of the project

2 Justification of the project

3 Promoters and their back ground 4 Regulatory framework 5 A map indicating location of the project and distance from severely polluted

areas 6 Project site location along with site map of 10 km area and site details providing

various industries, surface water bodies, forests etc. 7 Plant Layout 8 Infrastructure facilities including power sources

9 Total cost of the project along with total capital cost and recurring costs

environmental pollution control measures

10 Present land use based on satellite imagery for the study area of 10 km radius.

11 Details of the total land and break-up of the land use for green belt and other uses

12 Location of National Park/Wild life sanctuary/Reserve Forest within 10 km radius of the project

13 List of products along with the production capacities 14 Maximum number of products and its production capacity to be manufactured

at a time (worst-case scenario) 15 Detailed list of raw material required and source, mode of storage and

transportation. 16 Explore the use of solvent other than benzene 17 Manufacturing process details along with the chemical reactions and process

flow chart. 18 Site-specific micro-meteorological data using temperature, relative humidity,

hourly wind speed and direction and rainfall is necessary 19 Ambient air quality monitoring at 7 locations within the study area of 10 km.,

aerial coverage from project site



20 One season site-specific micro-meteorological data using temperature, relative

humidity, hourly wind speed and direction and rainfall and AAQ data (excluding monsoon season) for PM2.5, PM10, SO2, NOx and VOCs including

21 The monitoring stations should take into account the pre-dominant wind direction, population zone and sensitive receptors including reserved forests. Data for water and noise monitoring should also be included

22 Air pollution control measures proposed for the effective control of gaseous emissions within permissible limits. Multicyclone followed by bag filter to be provided to boiler to control particulate emissions

23 Name of all solvents to be used in the process and details of solvent recovery system.

24 Design details of ETP, incinerator, boiler, and scrubbers/bag filters etc. 25 Details of water and air pollution and its mitigation plan

26 An action plan to control and monitor secondary fugitive emissions from all the

Sources 27 Determination of atmospheric inversion level at the project site and assessment

of ground level concentration of pollutants from the stack emission based on Site-specific meteorological features

28 Air quality modelling for proposed plant

29 Action plan for Zero Liquid Discharge of effluent should be included. Segregation of the Wastewater should be based on the pollution load and high TDS effluent should be treated in MEE

30 Ground water quality monitoring minimum at 7 locations should be carried out. 31 Geological features and Geo-hydrological status of the study area and ecological

status (Terrestrial and Aquatic)

32 The details of solid and hazardous wastes generation, storage, utilization and disposal particularly related to the hazardous waste calorific value of hazardous waste and detailed characteristic of the hazardous waste. Action plan for the disposal of fly ash generated from boiler should be included

33 Precautions to be taken during storage and transportation of hazardous chemicals should be clearly mentioned and incorporated

34 Membership for the disposal of liquid effluent in CETP or Zero Liquid discharge action plan and solid/hazardous waste in TSDF.



35 An action plan to develop green belt in 33 % area

36 Occupational health of the workers needs elaboration including evaluation of

Noise, heat, illumination, dust, any other chemicals, metals being suspected in Environment and going into body of workers either through inhalation, ingestion or through skin absorption and steps taken to avoid musculo-skeletal disorders (MSD), backache pain in minor and major joints, fatigue etc. Occupational Hazards specific pre-placement and periodical monitoring should be carried out. Socio-economic development activities should be in place

37 Note on compliance to the recommendations mentioned in the CREP guidelines

38 Detailed Environment management Plan (EMP) with specific reference to details of air pollution control system, wastewater management, monitoring frequency, responsibility and time bound implementation plan for mitigation measure should be provided

39 Any litigation pending against the project and/or any direction/order passed by any Court of Law against the project, if so, details thereof

40 A tabular chart with index for point wise compliance of above TORs

# S.M.Labs-III

117

PROJECT REPORT

ON MANUFACTURE OF

BULK DRUGS AND INTERMEDIATES

S.M.Labs Pvt.Ltd.

OFFICE

S.M.Labs Pvt. Ltd. Plot No.C-5, IDA, Moula Ali

Hyderabad-500040.

# S.M.Labs-III

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CONTENTS

A. Glimpse

B. Brief Details of the Project

C. About Promoters & group concern

D. Product Description

E. Market Survey

F. Infrastructure facilities

G. Technical Know-How

H. Selling and Marketing Arrangement.

I. Swot Analysis

J. Risk factors and mitigation

K. Proposed Layout of Plant

# S.M.Labs-III

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G L I M P S E

Name of the Unit : S.M.labs Pvt Ltd. UNIT-III

Constitution : PRIVATE LIMITED

.

Proposed Location of Unit : Survey Nos: 1058,1059,

Machanpally Village

Bommalaramaram Mandal,

Nalgonda (Dt),

Andhra Pradesh.

Corporate Office : S.M.Labs Pvt. Ltd Plot No.C-5, IDA, Moula Ali

Hyderabad-500040.

Line of Activity : Manufacturing of Bulk Drugs & Intermediates . Proposed Capacity : 576 TPA Managing Director : 1. Sri M.Malla Reddy Director 2. G. Manikya Reddy Director 3. Madhukar Reddy 4. Rami Reddy 5. Maheswari

# S.M.Labs-III

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COST OF PROJECT:

Particulars Amount Rs in laks

Land 60.00 Building, Civil works& site development 320.00

Plant and Machinery 811.30 Furniture, Fixtures and other assets 17.40

Preliminary Pre operative 40.00 Liasoning work 20.00

Marginal money for working capital 30.00 Total 1298.70

Means of Finance Promoters Capital 450.00

Term loan 848.70 Total 1298.70

Brief Details of the Project: S.M.Labs Pvt.Ltd Unit-III. is incorporated by technocrats of varied experience, with the

main object of producing Bulk drug, Bulk drug intermediates for MNCs, with its

registered Office situated in Hyderabad, considered as capital of Drugs and

Pharmaceutical companies in India. The Company acquired 7 acres 17.50 Guntas of

land in Sy.Nos.1058 & 1059, Machanpally Village, Bommalaramaram Mandal,

Nalgonda District, Andhra Pradesh.

The company is planning to set-up in house R & D facility to develop new products.

The plant is designed for production of any product at any time, depending upon

prevailing demand, without making any major alteration to the equipment.

Land & site development: The Company acquired 7 acres 17.50 Guntas of land in Sy.Nos.1058 & 1059,

Machanpally Village, Bommalaramaram Mandal, Nalgonda District, Andhra Pradesh.

Out of the 30068 Square Meters of land acquired, the company proposes to utilize

around 1854 SQM of land towards establishing the manufacturing facilities,

administrative block, utilities and storage areas including future expansion. The

company has allocated the balance area of 17864.94 SQM for green-belt development.

# S.M.Labs-III

121

Building and Civil Work: The company has planned to construct the basic structures required for housing the

machinery & equipment, stores at a cost of Rs. 1298.70 lakhs. Cost for Civil works is

around 320.00 Lakhs. The buildings are planned to complete before December - 2014

for erecting the machinery & equipment. A detailed statement of area-wise civil works

completed by the Company as on date is prepared.

Plant & Machinery:

All the Plant and Machinery required for the proposed project would be procured

indigenously and the Cost for the equipment is around 811.30 Lakhs.

Furniture fixtures and other Assets: The furniture and fixture proposed to be purchased include production furniture, fixture

involving production tables, workers stools, office cabinets and racks, executive tables,

chairs, office filling cabinets. Vehicles will be purchased for facilitating movements or

workers and materials.

Implementation Schedule:

Activity Time frame for completion

Acquisition of land and development

Land Acquired

Construction of factory buildings

To Be Started after Obtaining CFE

Plant and Machinery. Process Equipment

-

Order to be placed after get the EC

-

- Commercial Production January-2015

# S.M.Labs-III

122

Preliminary and preoperative expenses: Preliminary and preoperative expenses are estimated at Rs. 40.0 lacs from the start up

time of this project till the commencement of commercial production. The expenses

include Rents, travel cost, salary and wages, legal and professional charges and

interest during the construction period. The cost also includes the expenses incurred in

the production trial runs before commencement of commercial production.

THE PROMOTERS:

Mr. M.Malla Reddy Reddy, Graduate in Chemistry, has work experience of more than

35years in different Bulk Drug industries.

Mr. G. Manikya Reddy, has work experience of more than 35 years in different Bulk

Drug industries

PRODUCT DESCRIPTION Bulk Drugs which are the active ingredients with medicinal properties and are the best

raw materials for making Bulk Drugs and Formulations which are specific dosage forms

of a Bulk Drug or of a combination of different Bulk Drugs and the final form in which the

drugs are sold i.e. syrups, injections, tablets, and capsules.

The Company proposes to manufacture the following products and their intermediates.

S.No Product Qty in Kgs/Month

1 Metformin HCl 20000.00

2 5-Cyano Pthalide 10000.00

3 Atorvastatin Calcium 2000.00

4 Lanseprazole 3000.00

5 Sildinafil Citrate 2000.00

6 Zidovudine 2000.00

7 Levo Cetirizine Di Hcl 2000.00

8 Escitilopram Oxalate 2000.00

9 Lamavudine 2000.00

10 Losartan Potassium 3000.00

# S.M.Labs-III

123

MARKET SURVEY The field of Bulk Drugs and intermediated is broad-based. It covers all products and

preparations used in the production of pharmaceutical formulations. The bulk drugs

industry segment in India has been able to establish its presence in the international

markets and more than 60 percent of its produce is exported. This segment has

managed tremendous growth, with production of only Rs. 0.18 billion in 1960, rising to

Rs. 10.0 billion by 2005 and hence meeting 70 percent of the domestic requirement.

The segment is a net foreign exchange earner producing export quality drugs; with bulk

drugs export accounting for 60 percent of the total pharma industry exports. Exports of

bulk drugs are growing by 30 percent per year. But given the size of the world market,

supply from India is miniscule – India’s exports account for only 1.0 percent of the

worldwide demand. In terms of the inputs used in production of drugs the industry faces

low cost of inputs at competitive rates helped by the presence of a well developed

chemical industry.

As the manufacture of most bulk drugs is neither capital intensive nor technology

intensive, process re-engineering encouraged the growth of production bases. There

are a large number of bulk drug manufacturers in India, including many small scale

industries. This has increased competition, leading to a drop in prices and consequently

lower margins. Most bulk drugs under the DPCO sell below the government

administered prices due to stiff competition and lower import tariffs.

PHARMACEUTICAL INDUSTRY – GLOBAL SCENARIO As per IMS Retail Drug Monitor, sales through pharmacies in thirteen leading markets

for the year to August 2003 are $ 298.7 Billion. According to the IMS World Review, in

2004, global audited sales of pharmaceuticals rose 8% (at a constant dollar rate) to

reach US $ 400.6 Billion. IMS world Review tracks actual sales of approximately 90% of

all prescription drugs and certain over-the-counter (OTC) products in more than 70

countries. Using proprietor data projection methodologies to estimate total global

pharmaceuticals sales, which grew to US $ 430.3 Billion in 2005. Despite economic

challenges in the worlds leading markets and a lower-than-normal number of new

product introductions, the global pharmaceutical industry experienced good growth in

2005.

# S.M.Labs-III

124

PHARMACEUTICAL INDUSTRY – DOMESTIC SCENARIO The Indian Pharmaceutical Industry today is in the front rank of India’s Science-based

industries with wide ranging capabilities in the complex field of drug manufacture and

technology. The Indian Pharmaceutical industry is estimated to be worth US $ 8.0

billions at present, growing at a CAGR of over 15 % annually. If India‘ s high

Economic growth rate holds steady, the pharmaceuticals market will triple to $ 24 billion

by 2015 and become one of the world` s top 10 markets according to a study by

McKinsey and company ,a leading management consulting firm. At a compounded

annual growth rate of 15.0 %, the absolute growth of $ 24 billion will be next to the

growth potential of the US and China, and in the same league as the growth in Japan

and Canada and the UK. Five factors will drive the growth of the Indian

Pharmaceuticals market over the next decade; Doubling of disposable incomes and

the increase in numbers of middle class households , significant expansion of medical

infrastructure, greater penetration of health insurance, a gradual shift in disease profile

and adoption of patented products, and finally population growth.

It ranks very high in the third world, in terms of technology, quality and range of

medicines manufactured. Playing a key role in promoting and sustaining development in

the vital field of medicines, the Indian Pharmaceutical Industry boasts of quality

producers and many units approved by regulatory authorities in USA and UK.

Internationally Companies associated with this sector have stimulated, assisted and

spearheaded this dynamic development in the past 50 years and helped to put India on

the pharmaceutical map of the world.

The Indian Pharmaceutical sector has more than 20,000 registered units. It has

expanded drastically in the last two decades. The leading 250 pharmaceutical

Companies control 70% of the market. The pharmaceutical industry in India meets

around 70% of the country’s demand for bulk drugs, drugs intermediates,

pharmaceutical formulations, chemicals, tablets, capsules, orals and injectables. There

are about 250 large units and about 8000 small Scale Units, which form the core of the

# S.M.Labs-III

125

pharmaceutical industry in India (including 5 Central Public Sector Units). These units

produce the complete range of pharmaceutical formulations, i.e. medicines ready for

consumption by patients and about 350 bulk drugs, i.e. chemicals having therapeutic

value and used for production of pharmaceutical formulations.

PHARMACEUTICAL INDUSTRY – Hyderabad SCENARIO Hyderabad has emerged as major drug manufacture city with a presence in global

market. Pharma industry in the state contribute more than one third to the country’s total

production. During 2005-06, the State produced bulk drugs and formulations worth US $

2.5 billion.

The exports from the state stood at US $ 1.0 billion in 2004-05 registering an annual

growth of more than 20%. The sector accounts for about 20 % of the total exports from

state.

Most of the companies have set up their R&D facilities in the state, thus making the

state the pharmaceutical capital of the country.

Hyderabad has developed as a major production center for bulk drugs due to the

location if the many major Pharmaceutical Industries such as Dr. Reddy’s Laboratories,

Aurobindo Pharma, Neuland Laboratories, Siris, Hetaro Drugs, Divis Labs, Natco

Pharma Limited, Matrix Labs, Nicholas Piramal etc., besides a large number of medium

and small industries manufacturing bulk drugs of all kinds.

To name a few Ge, AstraZeneca, Biocon, Cipla, Strides Arcolab, Himalaya drugs,

Karnataka antibiotics and pharmaceuticals ltd, Hinkle and Micro labs.

In support of this growth in Hyderabad and Bangalore, many basic chemical units and

drug intermediate units have also come up to meet the input requirements of Bulk Drug

manufacturing Companies. Large numbers of these units are still dependent on supply

of basic chemicals mainly from Mumbai, Gujarat and other parts of the country involving

heavy expenditure on transport and transit risks.

# S.M.Labs-III

126

So, considering the above factors, it is assured that setting up of basic drug

intermediate unit near Hyderabad will be of better prospect as we can meet the needs

of the Bulk Drug units located in and around Hyderabad. The products can be supplied

to the bulk consumers speedily and at lower prices reducing transport cost and time and

transit risks. The products can also be exported easily of proper marketing tie-ups are

made with the overseas bulk drug manufacturers in the due course as there is good

export potential for the basic drugs and intermediates.

UTILITIES a) Power Requirement of power and its arrangements: The company 850 H.P. power connection required for the proposed project from state

electricity board. The company also proposes to acquire 2 DG sets of 250 KVA as

standby arrangement.

b) Water Requirement of Water The unit requires about 128.56 KLD of water per day for process and other uses. The

area has good ground water source and the required amount of water can be obtained

by Bore well.

C) Boiler The company proposes to install 4MT/Hr X 2 Nos coal fired boilers.

c) Man power: The man power requirement of project is as under:

Particulars No. of employees

Functional Area

Key managerial staff 5 Finance, Marketing, Production, Quality control, R&D, Logistics etc.

Administration 15 Office work

# S.M.Labs-III

127

Skilled and semi skilled

40 Production Process, Maintenance, stores, Safety.&Un skilled workers

Total 60

Qualified and Skilled man power is available in and around Visakhapatnam and

Hyderabad both on permanent and temporary basis. We can also utilize services of

experts on ad-hoc basis for production of specialty products.

The company is planning to have good team of employees in all areas. Looking in to

long term planning, company will take all the necessary steps to develop a good team of

work force. The company will provide all basic amenities to staff such as Medical

Health, children education, transport, canteen facility, transport, clothing, financial

assistance, family welfare etc.

The company will organize training classes for all the staff in the areas of Process up

gradation, Quality control, cost reduction techniques, safety etc.

d) EFFLUENT (WASTEWATER), SOLID WASTE TREATMENT & DISPOSAL:

The industry shall adopt and follow an environmental management plan for abatement

of pollution and overall enhancement of the quality of environment in and around the

unit.

About 65.33 KL / day of effluent (wastewater) is generated from process and utilities.

The Company proposes to have a full pledged Effluent Treatment Plant (ETP) to treat

the effluent as per the norms.

Part of the treated effluent would be recycled and used for the process.

Part of treated effluent is sent for forced evaporation for final treatment. The residue

collected from forced evaporation and solid waste would be stored in HDPE

drums/Bags and disposed to TSDF facility.

e) GREEN BELT DEVELOPMENT: Green belt with selected perennial plant species developed in all around the site. This is

to be considered as an essential requirement against pollution though it may add to the

initial costs of the project. The green belt is considered essential because of the

following:

# S.M.Labs-III

128

• Plants act as pollutant sinks

• Green belt helps in noise attenuation

• Green belt balances ambient oxygen and carbon dioxide levels

• Green belt leads to a significant drop in air temperature near the manufacturing

shed.

TECHINCAL KNOW-HOW

The process of manufacturing Bulk drug Intermediates is semi-automatic with proven

technology. The process requires supervision of experienced in-charge to control yield

and quality. No specialized know-how is required for the process. The input mix is

standardized and the output is standardized in weight.

To supervise day to day production process, the company will appoint technically

qualified and experienced persons having relevant experience in the line of

manufacturing of Bulk drug intermediates.

The Unit will have well experienced, skilled and dedicated work force.

Selling and Marketing Arrangement:

The Company, by virtue of its well experienced directors in the field of Bulk drugs and

pharmaceuticals, has well established market connections. The company directors have

good relations with top executives of many reputed pharma companies and traders by

virtue of which fresh orders can be organized at any given time. Many recognized

companies assured their orders to the company and many more orders are expected

based on the completion of facility and regular production.

Our products and their intermediates are used in many organizations, and it is proposed

to enter into long term contract with these organizations. To name a few

# S.M.Labs-III

129

S.No. Name of the Company/trader 1 Hetro Drugs – Hyderabad 2 Lee Pharma Ltd-Hyd 3 Vijaya sri organics –Hyd 4 Sharon bio-medicine Ltd 5 Cipla Ltd-Mumbai 6 Carnivallis ltd-Hyd 7 Dr.Reddy’s Ltd-Hyd 8 Zydus cadila-Mumbai 9 Lifeline industries-Mumbai

10 Micro labs-Bangalore 11 Auctus Pharma Limited 12 Hinkle Pharma 13 Cipla 14 Astra Zeneca

Also, the Company proposes to have its own market network by appointing experienced marketing staff and dealers to sell the products. The company also approached many prospective buyers who have assured to give their requirement on conversion basis (Buy back arrangements) so that the company can have both self products and conversion market also. This will enable the company to have better control in plant operation, better market and financial flexibility. SWOT Analysis Strengths:

• The Promoters are technically qualified, well experienced and financially sound besides possessing the required managerial competence and business skills to make proposed project and successful and profitable venture.

• Procurement of raw material is very easy, since Hyderabad and Bangalore being

major pharma production center in India.

• The Project is located near Hyderabad and Mumbai the Pharma hub of India.

• Well Developed Industry with Strong Manufacturing Base and present industry conditions are favorable.

• Access to pool highly trained scientists.

• Competencies in technology and process development • Cost competitiveness in Global Market.

# S.M.Labs-III

130

Opportunities:

• Significant Export potential

• Licensing deals with MNCs

• Marketing alliances to sell MNC products in domestic market

• Contract manufacturing arrangements with MNCs

• Supply of generic drugs to developed markets Threats:

• Product patient regime poses serious challenge to domestic industry unless it invests in research and development.

• R&D efforts of Indian pharmaceutical companies hampered by lack of enabling

regulatory requirement. For instance, restrictions of animal testing outdated patent office.

• Drug Price Control Order puts unrealistic ceilings on product prices and

profitability and prevents pharmaceutical companies from generating investible surplus.

• Lowering of tariff protection

• The new MRP based excise duty regime threatens the existence of many small

scale pharma units, especially in the states of Andhra Pradesh and Maharashtra that were involved in contract manufacturing for the larger, established players. These companies are now shifting their manufacturing from these states to states like Himachal Pradesh, Uttaranchal that enjoy tax holidays.

# S.M.Labs-III

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Risk Factors and mitigation 1. The company is promoted by first generation entrepreneurs Though the Company is promoted by first generation entrepreneurs, the Promoters are technically qualified, well experienced and financially sound besides possessing the required managerial competence and business skills to make proposed project a successful and profitable venture. Further the Company has identified and proposes to appoint professionals in key areas of Production, Research & Development, marketing, logistics and Finance. 2. The Company operates in a globally competitive business environment. Growing competition may force the company to reduce the prices of its products and services, which may reduce its revenues and margins and/or decrease its market share, either of which could have a materially adverse effect on its business, financial condition and results of operations. The company aims to keep abreast with the dynamic business scenario and will broad-based its product mix. The Company, continuous R&D activities, will develop better process technology, improved process yield, sourcing of raw material at competitive price and development of new products/processes. 3. The prices of Raw Material/solvent consumed by the Company are susceptible to volatility. A majority of these raw materials are basic chemical, the demand for which is not dependent on demand by pharmaceutical industry. The other industries, which are generally much bigger consumer of such chemicals, tend to determine market prices of such basic chemicals; such volatility may affect company’s profitability. The raw materials consumed are general chemicals and are available in India as well as in many countries around the world at competitive prices. The company does not see any problem in procuring the raw material/solvent at competitive prices. 4. Expansions: Enhancement in production capacity by primary/main producers in our country may drive the industry into excess production. All the major producers are having plans to go for expansion in the production facilities. The other primary producers are having high fixed overheads and their market is through dealers. But the Company is having established market connections

Documents

M/s. S. M. Labs (P) Ltd., Unit - IIIenvironmentclearance.nic.in/writereaddata/form-1/0_0_09_Dec_2013... · M/s. S. M. Labs (P) Ltd., Unit - III Prepared by Rightsource Industrial