M/s. VPL CHEMICALS PVT. LTD., #27, Behind “The Club ...€¦ · 4.2 Land form, land use and...

1

FEASIBILITY REPORT FOR THE PROPOSED EXPANSION/MODIFICATION OF APIs MANUFACTURING

INDUSTRY

At

Plot No. 64, Sompura Industrial Area, Dabaspet, Nelamangala Taluk,

Tumkur Road, Bangalore, Karnataka

For

M/s. VPL CHEMICALS PVT. LTD., #27, Behind “The Club”

Nayandahalli, Mysore Road, Bangalore

Environmental Consultants

K.R.Sree Harsha, # 3391, 6th Main, 3rd Cross, RPC Layout,

Vijayanagar II Stage, Bangalore – 560 040

Tele Phone : 080 23141679

2

Contents Sl. No. Description Pg. no

1 CHAPTER 1-EXECUTIVE SUMMARY 1-14

2 CHAPTER 2- INTRODUCTION OF THE PROJECT/ BACKGROUND INFORMATION

15

2.1 Introduction of project proponent 15

2.2 Brief description about the nature of the project 16

2.3 Need for the project and its importance to the country and/ region

16

2.4 Demand supply gap, imports vs ingredients production 18

2.5 Expert possibility 18

2.6 Domestic/Export Markets 18

2.7 Employment generation due to the project 18

3 CHAPTER 3- PROJECT DESCRIPTION

3.1 Type of project 19

3.2 Location of the industry 19

3.3 Basis of selection the site 20

3.4 Size/ magnitude of operation 21

3.5 Products manufactured 21

3.5.1 Fexofenadine HCl 21

3.5.2 Ambroxol HCl 27

3.5.3 Amlodipine Besylate 31

3.5.4 Fluconazole 36

3.5.5 Febuxostat 40

3.5.6 Pregabalin 43

3.5.7 Dabigetran 48

3.5.8 Verapamil HCl 52

3.5.9 Terfenadine 55

3.6 Raw materials 59

3.6.1 Storage facility for raw materials and products 62

3.6.2 Machinery and equipment details 63

3.7 Resource optimization/ recycling and reuse envisaged in the project

65

3.7.1 Solvent recovery and reuse 65

3.7.2 Solvent Recovery System 66

3.8 Hazardous Raw Materials Used In The Manufacturing Process 66

3.8.1 Hazardous waste generation and its management during the manufacturing process

67

3.8.2 Hazardous Waste Quantity and Disposal Details 68

3.9 Domestic solid waste reuse 68

3.10 Water, energy/ power requirement and source 68

3.10.1 Water 68

3.10.2 Power 68

3.11 Wastes generated and scheme for their management/ disposal 68

3.11.1 Water demand and wastewater/ effluent discharge 68

3

3.12 Product wise water consumption and discharge 70

3.12.1 Waste Water Characteristics 71 3.12.2 Treatment Scheme for Industry Waste Water 71 3.13 Air pollution sources 73

3.13.1 Scrubbing System Details 73

3.14 Noise generation and its management 74

3.15 Solid waste generation and management 74

3.16 Schematic representations of the feasibility drawing 75

4 CHAPTER 4- SITE ANALYSIS 76

4.1 Connectivity 77

4.2 Land form, land use and ownership 77

4.3 Topography 77

4.4 Existing land use pattern 78

4.5 Existing infrastructure 78

4.6 Soil Classification 78

4.7 Climatic Data From Secondary Sources 79

4.7.1 Temperature 79

4.7.2 Relative Humidity 79

4.7.3 Rainfall 80

4.7.4 Atmospheric Pressure 80

4.7.5 Inversion height 80

4.7.6 Cloud Cover 80

4.7.7 Wind 80

4.8 Social infrastructure available 81

5 CHAPTER 5- PLANNING BRIEF

5.1 Planning concept 86

5.2 Population projection 86

5.3 Land use planning 86

5.4 Assessment of infrastructure demand 86

5.4.1 Water supply and sewerage infrastructure 87

5.5 Amenities/Facilities 87

6 CHAPTER 6- PROPOSED INFRASTRUCTURE

6.1 Industrial area (processing area) 88

6.2 Residential Area (Non Processing Area) 88

6.3 Green belt 88

6.4 Social infrastructure 88

6.5 Connectivity 88

6.6 Sewerage system 88

6.7 Industrial waste management 88

6.8 Solid waste management 89

6.9 Power requirement and supply source 89

7 CHAPTER 7- REHABILITATION & RESETTLEMENT PLAN 90

8 CHAPTER 8- PROJECT SCHEDULE & COST ESTIMATES 91 8.1 Time schedule 91

8.2 Estimate project cost 91

9 CHAPTER 9- ANALYSIS OF PROPOSAL 92

4

List of tables

Table no.

Description Pg. no

3.1 APIs are proposed to be manufactured 21

3.2 Raw materials requirement 59

3.3 Details of storage facilities 62

3.4 List of the machinery and equipments 63

3.5 Solvent recovery 65

3.6 Hazardous raw materials 66

3.7 Quantity of process residue generation from solvent recovery and Carbon waste generated from manufacturing process

67

3.8 Hazardous Waste Quantity and Disposal Details 68

3.9 Water Consumption and Discharge

69 3.10 Sewage/effluent treatment and discharge

70 3.11 Product-wise water consumption for process and effluent

discharge

70

3.12 Waste Water Characteristics

71 3.13 Air pollution sources, fuel consumption and chimney height

details 73

3.14 Solid waste generation 74

4.1 Connectivity from the project site 76

4.2 Existing land use pattern 78

4.3 Meteorological Data of Bangalore for the Year 2015 79

4.4 List of Infrastructural Facilities in the Surroundings 81

5.1 Land use pattern 86

List of figures

Fig. No. Description Pg. no

3.1 Google Map Showing Project Site 19

3.2 Map showing the Project Site Location on District Map of Bangalore

20

3.3 Water balance chart 72

3.4 Scrubbing System 74

4.1 Google map showing connectivity 76

4.2 Topo Map 77

4.3 Wind rose diagrams 82

FORM I 1

APPENDIX I

(See paragraph – 6)

FORM 1

(I) Basic Information

1 Name of the Project? M/s. VPL Chemicals Pvt. Ltd.

2 Sl. No. in the schedule? Serial No. 5(f) of schedule

3 Proposed capacity/ area/ length/ tonnage to be handled/command area/lease area/number of wells to be drilled?

The following Active Pharmaceutical Ingredients (APIs) & Intermediates are proposed to be manufactured ( Change in products)

APIs Production capacity

(kg/month)

Fexofenadine HCl 4500

Ambroxol HCl 4500

Amlodipine besylate 4500

Fluconazole HCl 4500

Febuxostat 1000

Pregabalin IP 3000

Dabigetran 3000

Verapamil HCl 3000

Terfenadine 3000

Plot area - 5058.57 SQM Built up area - 2430 m2

4 New / Expansion / Modernization? Expansion/ Modification project

5 Existing capacity / Area etc.? Existing production capacity

APIs & Intermediates

Production capacity

(kg/annum)

Amyl meta cresol 600

Benazepril Hydrochloride

600

Fexofenadine hydrochloride

1200

Ambroxol hydroxide

6000

Oxcarbazepine 1200

P-nitrobenzene sulfonyl chloride

1200

2,4- Dichlorobenzyl 16800

6 Category of project i.e. `A` or `B`? B

7 Does it attract the general condition? If yes, please specify.

No

8 Does it attract the specific condition? No

FORM I 2

If yes, please specify.

9 Location M/s. VPL Chemicals Pvt. Ltd., Plot no. 64, Sompura Industrial area, dabaspet, Nelamangala Taluk, Tumakuru Road, Bangalore

Plot/Survey/Khasra no. Plot no. 64

Village dabaspet

Thesil Nelamangala

District Bengaluru

State Karnataka

10 Nearest railway station/airport along with distance in km?

Dabaspet railway station at a distance of about 2 km from the project site.

11 Nearest Town, City, District Headquarters along with distance in km?

Bangalore

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

Bangalore

13 Name of the applicant Shri Shashidhar G Patil

14 Registered address M/s. VPL Chemicals Pvt. Ltd., # 27, Behind “The Club” Nayandahalli, Mysore Road, Bangalore-560039

15 Address for correspondence: M/s. VPL Chemicals Pvt. Ltd., # 27, Behind “The Club” Nayandahalli, Mysore Road, Bangalore-560039

Name Shri Shashidhar G Patil

Designation (Owner/Partner/CEO) Managing Director

Address As above

Pin Code Bangalore – 560 064

E – mail -

Telephone No. +91-80-27734119

Fax No. +91-80-28601336

16 Details of alternative sites examined, if any? Location of these sites would be shown on a topo sheet.

Village – District – State 1. 2. No alternative sites are examined.

17 Interlined Projects NA

18 Whether separate application of interlined project has been submitted?

NA

19 If yes, date of submission? NA

20 If no, reason? Proposed project is expansion/modification of Active Pharmaceutical Ingredients (APIs) &

FORM I 3

Intermediates manufacturing industry.

21 Whether the proposal involves approval/clearance under: a) The Forest (Conservation) Act 1980? b) The wildlife (Protection) Act, 1972? c) The C R Z Notification, 1991? If yes, details of the same and their status to be given.

No No No

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

None

23 Forest land involved (Hectares)? None

24 Whether there is any litigation pending against the project and/or land in which the project is proposed to be set up?

a) Name of the court b) Case No. c) Orders/directions of the court,

if any and its relevance with the proposed project.

None

Screening Category: The proposed project is under category 5(f) as per amended EIA notification September 14th 2006

Capacity corresponding to sectoral activity (such as production capacity for manufacturing, mining lease area and production capacity for mineral production, area for mineral exploration, length for linear transport infrastructure, generation capacity for power generation etc.)

(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.)

Sl. 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 The proposed project is an expansion/modification proposal in existing & on-going consented industry and also the industry is developed in KIADB Industrial area. Therefore there will not be any permanent or temporary changes in land use, though the proposed industry is likely to increase the intensity of land use.

FORM I 4

1.2 Clearance of existing land, vegetation and buildings?

No NA

1.3 Creation of new land uses?

No Creation of new land uses from the proposed project is not expected as the intended use of the plot is for the industrial purpose. 1.4 Pre-construction investigations e.g.

bore houses, soil testing? No The proposed expansion/modification

of the project will be done in existing facility.

1.5 Construction works?

Yes The proposed project does not involve any construction activity as the proposed expansion and modification will be done in the existing facility, hence, will not have any major impact on the environment.

1.6 Demolition works?

No Demolition works are not expected in the proposed expansion project.

1.7 Temporary sites used for construction works or housing of construction workers? (Details of labor camps, no. of labors, no. of toilets, bath rooms, medical facilities for labors, safety measures for labors, nursery for labors children).

No The proposed project does not involve any construction activity as the proposed expansion and modification will be done in the existing facility, hence, construction workers are not required.

1.8 Above ground buildings, structures or earthworks including linear structures, cut and fill or excavations? (Calculation for earth work estimation).

Yes The proposed project does not involve any construction activity as the proposed expansion and modification will be done in the existing facility, hence, construction work not envisaged.

1.9 Underground works including mining or tunneling?

No NA

1.10 Reclamation works? No NA

1.11 Dredging? No NA

1.12 Offshore structures? No NA

1.13 Production and manufacturing processes?

Yes Manufacture of Active Pharmaceutical Ingredients (APIs) & Intermediates Existing scenario


(kg/month)


Benazepril Hydrochloride

600

Fexofenadine hydrochloride

1200

FORM I 5

Ambroxol hydroxide

6000

Oxcarbazepine 1200


1200

2,4- Dichlorobenzyl 16800

Emerging scenario

APIs & Intermediates Production capacity

(kg/annum)

Fexofenadine HCl 4500

Ambroxol HCl 4500

Amlodipine besylate 4500

Fluconazole HCl 4500

Febuxostat 1000

Pregabalin IP 3000

Dabigetran 3000

Verapamil HCl 3000

Terfenadine 3000

1.14 Facilities for storage of goods or materials?

Yes Storage facilities are proposed for

Raw materials, APIs (details in section 3.6.1, Chapter 3 of PR appended)

Industrial effluents (details in section 3.6.1, Chapter 3 of PR appended)

Hazardous wastes (details in section 3.8.2, Chapter 3 of PR appended).

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

Yes Liquid waste

Construction phase:

No construction phase Operation phase:

Domestic sewage: The domestic sewage generated during operation phase (2000 L/day) will be discharged into septic tank and soak pit Industrial effluent:

The industrial wastewater (11.8 KLD) will be treated in Effluent treatment Plant (ETP) with MEE followed by RO filtration for treatment and reuse

FORM I 6

Solid waste Occupancy phase: Domestic solid wastes: Collection and segregation at the source composted and used as manure for landscape development Hazardous wastes: The hazardous wastes generated during the process of manufacture of different APIs and sludge from forced evaporators are stored at hazardous waste storage area and sent to M/s. Karnataka Waste Management Project (having authorization from KSPCB for collection, transportation, storage and disposal of hazardous waste – TSDF facility) for scientific disposal. The solid waste details are appended in section 3.13 & 3.15, Chapter 3 of PR appended.

1.16 Facilities for long term housing of operational workers?

No No long term housing plan for the operational workers is planned in the proposed project. The local population residing in the surrounding area of the project site is expected to find employment opportunities for various maintenance needs of the Project.

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

No NA

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

No NA

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

No NA

1.20 New or diverted transmission lines or pipelines?

No NA

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

No NA

1.22 Stream crossings? No NA

1.23 Abstraction or transfers of water Yes The source of water supply for the

FORM I 7

form ground or surface waters? project is from Bore-well water supply from project site

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

No NA

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

Yes

1.26 Long-term dismantling or decommissioning or restoration works?

No NA

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

No NA

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

Yes There will be influx of people during the occupancy phase. Occupancy phase

Existing scenario – 50 After Expansion proposal – 50

1.29 Introduction of alien species? No NA

1.30 Loss of native species or genetic diversity?

No NA

1.31 Any other actions? No NA

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):

Sl. No.

Information/checklist confirmation Yes/No

Details

2.1 Land especially undeveloped or agricultural land (ha)

No The proposed project is Expansion in existing & on-going consented unit. Land is already available and developed for industrial use. No additional land is required. Also it is in KIADB Industrial area. The total site area is 0.5 ha

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

Yes The source of water for the project is bore-well water supply. Total fresh water requirement is about 6.5 KLD. Details are appended in section 3.3, Chapter 3.11 of the PFR report appended.

2.3 Minerals (MT) No NA

FORM I 8

2.4 Construction material – stone, aggregates, sand/soil (expected source – MT)

No No construction activity

2.5 Forests and timber (source – MT) No No construction activity

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

Yes Power requirement As the proposed project is Expansion in existing & on-going consented unit the required power (of 150 kVA) is available and no additional power is required for manufacturing the proposed additional products.

DG sets are used during occupancy phase which serves as back-up power supply during power failure. Existing scenario: 250 kVA… 1 No Emerging scenario: 15 kVA…. 1 No

Fuel requirement 58.75 for 250 kVA DG set and 3.5 L/hr for 15 kVA DG set.

2.7 Any other natural resources? (use appropriate standard units)

No NA

FORM I 9

3. 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

Sl. 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 Details of the hazardous raw materials used and hazardous wastes generated are in section 3.6 & 3.8.2, Chapter 3 of PR appended.

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

No NA

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

Yes The implementation of the proposed expansion project is beneficial both socially and economically to its local populace, as it will create both long term and short term employment opportunities.

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

No NA

3.5 Any other causes? No NA

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

(MT/month)

Sl. No.

Information/Checklist confirmation Yes/ No


4.1 Spoil, overburden or mine wastes? No NA

4.2 Municipal waste (domestic and or commercial wastes)?

Yes Quantities of solid waste generated from the project during operation phase are detailed in section 3.15 Chapter 3 of PR appended.

4.3 Hazardous wastes (as per Hazardous Waste Management Rules)?

Yes DG sets: Spent oil from DG sets category 5.1. About 200 L/annum of spent oil is generated which is sent to authorized spent oil reprocessor with manifest as per notification of Hazardous Waste (Management and Handling Rules). Details of hazardous raw materials used and hazardous wastes generated during the manufacturing processes are in

FORM I 10

section 3.8.2 of Chapter 3 in PR appended.

4.4 Other industrial process wastes? NO No other industrial waste is generated

4.5 Surplus product? No NA

4.6 Sewage sludge or other sludge from effluent treatment?

No About 38.7 kg/day of sludge is generated from forced evaporators which is proposed to be handed over to TSDF facility for scientific disposal.

4.7 Construction or demolition wastes? No No construction activity is proposed

4.8 Redundant machinery or equipment? ?

No NA 4.9 Contaminated soils or other

materials? Yes The following measures are adopted to

control soil contamination. Prevention of spillage and leakage of oils, providing kerb stones, lined gutter and oil traps.

4.10 Agricultural wastes? No NA

4.11 Other solid wastes? No NA

5. Release of pollutants or any hazardous, toxic or noxious substances to air (kg/hr)

Sl. No.



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

Yes The sources of air pollution from the project are generators, boilers and thermic fluid heaters installed during occupancy period.

Air pollution source

SPM (g/s)

SO2

(g/s) NOx

(g/s)

DG set

250 kVA 0.016667

0.016667

0.51111

15 kVA 0.001 0 0.030667

Boiler – 2 Ton

0.11736 1.706 0.2988

1 Ton (Proposed)

0.05904 0.8582 0.150333

5.2 Emissions from production processes? Yes The waste gases generated during manufacturing process are passed through a stack provided with a packed column scrubber before letting out into the atmosphere.

5.3 Emissions from materials handling including storage or transport?

No NA

FORM I 11

5.4 Emissions from construction activities including plant and equipment?

No No construction activity is required as the proposed expansion will be done in existing facility. EMP during occupancy phase is appended in report

5.5 Dust or odors from handling of materials including construction materials?

No No construction activity is required as the proposed expansion will be done in existing facility.

5.6 Emissions from incineration of waste? No NA

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

No NA

5.8 Emissions from any other sources? No NA

6. Generation of noise and vibration, and emissions of light and heat

Sl. No.

Information/Checklist confirmation

Yes/ No


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

Yes Operation of generators, boilers and scrubber during occupancy phase. They are provided with acoustic enclosures/silencer. Further noise attenuation by way of planting peripheral trees and noise barriers at the project boundary is also ensured.

6.2 From industrial or similar processes?

Yes Same as mentioned in 6.1 above is applicable.

6.3 From construction or demolition? Yes Noise generation due to demolition activities is not anticipated as no demolition works are involved.

6.4 From blasting or piling? No NA

6.5 From construction or operational traffic?

Yes Vehicular movement by the employees during occupancy phase. The details of mitigation measures planned to reduce the noise level are detained in Environmental Management Plan during operational phase

6.6 From lighting or cooling systems? No NA

6.7 From any other sources? No NA

FORM I 12

7. Risks of contamination of land or water from release of pollutants into the ground or into sewers, surface waters, groundwater, coastal waters or the sea:

Sl. No.

Information/Checklist confirmation Yes /No


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

Yes Appropriate management measures to prevent contamination of land, water is detailed in Chapter 1 of PFR report appended under water and land environment.

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

No Domestic sewage Sewage generated during operation phases are treated in septic tank and soak pit. Industrial effluent The industrial wastewater will be treated in Effluent treatment Plant (ETP) with MEE followed by RO filtration for treatment and reuse.

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

No NA

7.4 From any other sources? No NA

7.5 Is there a risk of long term build-up of pollutants in the environment from these sources?

No NA

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

human health or the environment

Sl. No.



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

Yes

8.2 From any other causes? No NA

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

No NA

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

Sl. No.


Details thereof (with approximate quantities/rates,

FORM I 13

wherever possible) with source of information data

9.1 Lead to development of supporting utilities, ancillary development or development stimulated by the Project which could have impact on the environment e.g.

• Supporting infrastructure (roads, power supply, waste or wastewater treatment, etc.) • Housing development • Extractive industries • Supply industries • Other

Yes Yes NA No Yes No

Net positive impact in terms of overall development of the area is expected from the proposed project. Direct & indirect employment opportunities are created due to expansion of this project. Manufacturing of APIs & Intermediates. The quantity proposed to be manufactured is detailed in section 2.1, Chapter 3 section 3.5 of PR report appended.

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

No NA

9.3 Set a precedent for later developments? Yes The proposed project is an expansion proposal in KIADB industrial area and therefore no major impacts are expected.

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

No NA

(II) Environmental sensitivity

Sl. No.

Areas Name/ identity

Aerial distance (within 15 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 NA

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

No No eco sensitive areas or water bodies within 5km from project site

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

No NA

4 Inland, coastal, marine or underground waters?

No NA

5 State, National boundaries? No NA

FORM I 14

6 Routes or facilities used by the public for access to recreation or other tourist, pilgrim areas?

No NA

7 Defense installations? No NA

8 Densely populated or built-up area? No Since the project is in an industrial area no densely populated or built-up area is located close to the project site.

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

No NA

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 NA

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 NA

“I hereby undertake that the data and information given in the application and enclosures are true to the best of my knowledge and belief and I am aware that if any part of the data and information submitted is found to be false or misleading at any stage, the project will be rejected and clearance, if any, given to the project will be revoked at our risk and cost. Date: 03.02.2016 Place: Bangalore

Shri Shashidhar G Patil M/s. VPL Chemicals Pvt. Ltd.,

# 27, Behind “The Club” Nayandahalli, Mysore Road,

Bangalore-560039 Signature of the applicant

With Name and Full address (Project Proponent / Authorized Signatory)

M/s VPL Chemicals Pvt. Ltd.,

Pre-Feasibility Report - 1 -

CHAPTER 1

EXECUTIVE SUMMARY

1.1 INTRODUCTION

1.1.1 Preamble

Amendment of the Environmental Impact Notification No. S.O. 60(E) dated 27.01.1994, issued

by the MoEF, Govt. of India has made mandatory under Schedule-I of EIA notification for 30

different activities to obtain NOC (No Objection Certificate) from the State Pollution Control

Board and Environmental Clearance from the Ministry of Environment & Forests, Govt. of

India. This amendment to the EIA Notification is effective from 14.09.2006.

As per the amended EIA notification dated 14th September, 2006 the API manufacturing

industry will fall under category B schedule 5(f). The proposed project is

Expansion/Modification of API manufacturing.

The proposed expansion and modifications envisages deletion of some of the existing and

addition of some product, which will be manufactured within the existing manufacturing

facilities. The effluent quality and quantity generation will marginally increase with 5 to 10 %

which will be treated in the existing Zero Discharge Plant (ZDP) having an adequate capacity

of 600 liters/hour. There is no additional process emissions except thermic fluid heater boiler,

which has an adequate stack height. Existing Zero Discharge Plant (ZDP).

M/s. VPL Chemicals Pvt.Ltd., #27, Behind “The Club” Nayandahalli, Mysore Road, Bangalore-

560039, intends to Expand and Modify the existing Active Pharmaceutical Ingredients (APIs)

manufacturing industry at Plot No. 64, Sompura Industrial Area, Dabaspet, Nelamangala

Taluk, Tumkur Road, Bangalore, Karnataka.

The present APIs manufactured are provided under Table 1.1

Table 1.1 Present API manufactured

APIs & Intermediates Production capacity (kg/annum)


Benazepril Hydrochloride 600

Fexofenadine hydrochloride 1200

Ambroxol hydrochloride 6000

Oxcarbazepine 1200


1200

2,4- Dichlorobenzyl alcohol 16800



Table 1.2 The Proposed APIs to be manufactured

Sl. No.

APIs Existing production capacity(Kg/Month)

Production capacity (kg/month)

Nature/ Type of product

1 Fexofenadine HCl 100 4500 ( After Expansion)

All products are API’s

2 Ambroxol HCl 500 4500 ( After Expansion)

3 Amlodipine Besylate

New Products

4500

4 Fluconazole 4500

5 Febuxostat 1000

6 Pregabalin 3000

7 Dabigetran 3000

8 Verapamil HCl 3000

9 Terfenadine 3000

Total - 31,000

1.1.2 Project at Glance

Sl.No. Details

1 Project Expansion and modification of Active Pharmaceutical Ingredients (APIs) manufacturing industry – “M/s. VPL Chemicals Pvt. Ltd.,”

2 Project developers M/s. VPL Chemicals Pvt. Ltd., # 27, Behind “The Club” Nayandahalli, Mysore Road, Bangalore-560039

3 Location of the site Plot no. 64, Sompura Industrial area, dabaspet, Nelamangala Taluk, Tumkur Road, Bangalore

4 Constitution of the Organization

Private Limited Company

5 Raw materials Details of the raw materials required by the industry is appended in Section 3.6. Chapter 3 of this report.

6 Product/s proposed to be manufactured with production capacities? #

The following APIs are proposed to be manufactured

Sl. No.


(kg/month)

Nature/ Type of product

1 Fexofenadine HCl 4500

All products are API’s

2 Ambroxol HCl 4500

3 Amlodipine Besylate 4500

4 Fluconazole 4500

5 Febuxostat 1000

6 Pregabalin 3000

7 Dabigatran 3000


9 Terfenadine 3000

Total 31,000

7 Project cost? For expansion Proposal 8 Lakhs



8 Total man power requirement during construction

phase occupancy

phase

Construction phase: No construction activity Operational phase: 50 employees.

9 Proposed trees to be planted?

Tress planted – 50 nos Trees proposed to be planted- 50 nos

10 Species of trees to be planted?

Silver Wood, Teak wood, Coconut, Asoka Trees, Mango trees, Cassia fistula, Alstonia scholaris, and several native species

11 Rain water harvesting tank details?

30 KLD Capacity

12 Groundwater recharging pits details?

Storm water recharge pits are provided

13 Elevation of the project site with respect to MSL?

933 m above MSL; Latitude: 13°13’'29.51"N; Longitude: 77°15'55.85"E

14 Total area of the project?

5058.57 SQM (about 1.25 Acres)

15 Ground water quality?

Portability of water is tested and can be used for drinking.

16 Noise levels? Noise levels are within the standard limits.

17 Facilities provided for the workers during construction phase at site?

1. Adequate potable drinking water supply 2. Septic tank and soak pit facility for treating wastewater generated from the workers.

1.1.3 Water Requirement and Wastewater Treatment and Discharge Details

Sl. No.

Particulars Details

A Water, wastewater details

1 Water supply sources Bore well water supply

2 Total water requirement 6.5 KLD

3 Total wastewater generated 13.6 KLD (11.8 KLD effluent + 1.8 KLD Domestic)

4 Treatment/Disposal details Effluent Treatment Plant (ETP) with Multiple Effect Evaporator (MEE) followed by RO Filtration.

B Air pollution details

1 Sources of air pollution Process sections, Boiler, DG set



2 Air pollution control units provided

* Packed column scrubbers for process sections with Chimney height of 15 m above RL. * DG set stack height as per the stack height calculation for 250 kVA is 12 m AGL and 15 kVA(proposed) 3m AGL * For agro based fuel boiler for 2 Ton and 1 Ton (proposed) combined stack height of 30.48 m above GL and with Mechanical dust collector. * Thermic Fluid Heater (TFH) of stack 10 m will be provided

C Solid/Hazardous wastes

1 Source of solid waste Domestic sources and Manufacturing process.

2 Total quantity of solid waste generated

Domestic solid waste – 3750 kg/annum Hazardous solid waste

Sl. no

Hazardous waste

Quantity kg/annum

Category

1 Residue from the manufacturing process

3,70,344 28.1

2 Spent Carbon 7,644 28.2

3 Waste oil generation from DG set

200 5.1

4 Inorganic salt from MEE.

52,800 34.3

3 Treatment/Disposal of solid wastes

* The domestic wastes are segregated at source and collected in bins. The organic portion of the solid wastes will be composted and recyclable portion will be disposed to the recycler for scientific recycling. * The disposal for various types of generated hazardous waste handling and management is detailed in Chapter 3, Section 3.8.2 of this report.



1.1.4 Water Requirement and Wastewater Treatment and Discharge Details I) Quantity of Water Required and Wastewater Generated The total quantity of water requirement for the industry is about 6 KLD. The break-up of the consumption of water is as presented in Table 1.3.

Table 1.3 Water Consumption and Discharge

Water consumed for Consumption (LPD)

Discharge (LPD)

(a) Domestic (toilet, canteen etc.) 2000 1800

(b) Gardening/Landscape development 350 -

(c) Industrial purpose

Process

1. RO plant and its reject 7200-5513=1687 (reject)

8873 (process effluent + Rejects)

a. Process consumption 5513

2. Washing/Cleaning 1500 1500

3. Boiler feed for 2 MT boiler 3000 100 (Blow down)+ DM reject 600 a. DM plant/rejects 600

4. Cooling tower – 2 nos. 1000-800 (Condensate)= 200

(make up water)

20

5. Scrubber – 1 no. 500 500

6. R & D 150 150

Total 16300 13543 or say 13600KLD

Note:

LPD = L/day; KLD = kilo liter/day. At any given time only one product will be manufactured. The excess quantity of process effluent generated is due to the reactions taking place

during the manufacturing process. Startup water requirement for industrial purpose is 13950. After recycling of

Evaporator condensate the fresh water requirement will be 4000 LPD.

ii) WASTEWATER TREATMENT AND DISPOSAL DETAILS The treatment methods and the final disposal of each type of wastewater generated is

appended in the table 1.4

Table 1.4 Sewage/wastewater treatment and discharge

Sewage/effluent generated from

Treatment provided Final disposal point

(a) Domestic Sewage is treated septic tank Disposed in Soak pit

(b) Industrial Full-fledged ETP with collection tanks of 10 KL capacity (4 no.s) are provided.

Industrial effluent is treated in Effluent Treatment Plant (ETP) with Multiple Effective Evaporator (MEE) followed by RO filtration for treatment, reuse.



1.1.5 Raw Materials The raw materials required for the manufacture of APIs are appended in the table 1.5 below. Raw materials as listed will be procured as per the production requirement.

Table -1.5 Raw Materials Requirement for manufacture of API Sl.

No. Product Raw materials Quantity required Solvents

required after recycling

kg/annum

kg/batch

kg/month kg/annum

1 Fexofenadine HCL

Methyl (Stage1) 273 4095 49140 -

Azacylonol 231 3465 41580 -

Potassium iodide 3 45 540 -

Sodium bi carbonate 117 1755 21060 -

Sodium Boro hydride 30 450 5400 -

Sodium hydroxide flakes

66 990 11880 -

HCL 300 3285 39420 -

methyl iso butyl ketone

1092 16380 196560 -

Hyflow 3 45 540 -

Activated Carbon 3 45 540 -

Purified water(stage 1)

681 10215 122580 -

Stage 2 138 2070 24840 -

Methanol(stage 2) 1089 16335 196020 19440

Stage 3 165 2475 29700 2700

Ethyl acetate 324 4860 58320 5400

Iso propyl alcohol 165 2475 29700 2700

2 Ambroxol HCL 2-amino-3,5-Dibromo Benzaldehyde

216 3240 38880 -

Trans 4-aminocyclohexnol

90 1350 16200 -

Sodium Borohydride 30 450 5400 -

Activated carbon 6 90 1080 -

Hy flow 3 45 540 -

HCL 54 810 9720 -

Purified water 765 11475 137700 -

Acetone 1800 27000 324000 25920

Methanol (Stage I)

1224 18360 220320 22140

3 Amlodipine besylate

Monomethylamine 786 11790 141480 -

Phathoylamlodipine 321 4815 57780 -

Benzene sulphonic acid

129 1935 23220 -

Activated charcoal 6 90 1080 -



Hy flow supercell 6 90 1080 -

Purified water (stage 1)

621 9315 111780 -

Stage 2 735 11025 132300 -

Methanol 1743 26145 313740 3240

Ethyl acetate 1743 26145 313740 1080

4 fluconazole Di-floro-tetra-aceto-phenone

348 5220 62640

Trimethyl solfoxonium iodide

156 2340 28080

1,2,4 triazole 156 2340 28080

Potassium hydroxide 225 3375 40500

HCL 249 3735 44820

Hyflow supercell 6 90 1080

Citric acid 9 135 1620

Purified water 870 13050 156600

Toulene 117 1755 21060 2700

5 Febuxostat Ethyl-2-(3-cyano-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylate

153 1530 18360

Febuxostat crude 130 1300 15600

NAOH 23 230 2760

HCL 62 620 7440

Acetone 1333.8 13338 160056 8004

Isopropyl alcohol 600 6000 72000 3540

Activated carbon 6 60 720

Celite 6 60 720

Water 3401 34010 408120

6 Pregabalin R-(-)-3- carbamoymethyl hexanoic acid

504 5040 60480

Hydrochloric acid 708 7080 84960

Sodium Hydroxide 330 3300 39600





7 Dabigetran 3-[(1-Methyl-2-{[4-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)- phenylamino]-methyl)-1H benzoimidazole-5- carbonyl)-pyridin-2-yl-amino]-propionic acid ethyl ester

15 150 1800

P-toluene sulphonic acid

4 40 480

Acetic acid 3 30 360

IPA 375 3750 45000

Hexa chlorofomate 4 40 480

Acetone 180 1800 21600

Potassium Hydroxide

2 20 240

Hydrochloric acid 0.1 10 120

Water 150 1500 18000

8 Verapamil HCL 2-(3,4- Dimethoxyphenyl)-3-methylbutanenitrile

324 3240 38880

N-(3-choloropropyl)-N-[2-(3,4-dimethoxyphenyl)ethyl]-N-methylamine

225 2250 27000

Sodamide 48 480 5760

HCL 183 1830 21960



Toluene (stage 1 ) 2163 21630 259560 9740

Stage 2 1686 16860 202320 1440

RO water 1050 10500 126000

Methanol 804 8040 96480

9 Terfenadine 1-(4-tert-butyl phenyl)-4-chloro-1-butanone

273 2730 32760

Azacyclanol 231 2310 27720

Potassium Iodide 3 30 360

Sodium bi carbonate 117 1170 14040



Sodium boro hydride 30 300 3600

HCL 138 1380 16560


Methanol 1347 13470 161640 3600

Ethyl Acetate 324 3240 38880 8280

* At any given time only one or two products shall be made

1.1.6 Solvent Recovery and Recycling

Various solvents will be used during the manufacturing process. The solvents proposed to be recovered and recycled during the process of recovering the solvent of such product are detailed in table 1.6 below.

Table 1.6 Solvent Recovery

Sl.No

Product Raw materials Quantity (kg/annum)

Recovered and recycled

Lost

1 Fexofenadine HCL Stage 1

Ethyl acetate 52920 5400

Stage 2 Methanol 176580 19440

Stage 3 Iso propyl alcohol 27000 2700

Methanol 27000 2700

Methyl iso butyl ketone

186840 9720

2 Ambroxol HCL Stage 1

Methanol 198180 22140

Stage 2 Acetone 298080 25920

3 Amlodipine besylate Stage 3

Methanol 310500 3240


4 fluconazole Toluene 18360 2700

5 Febuxostat Iso propyl alcohol 68460 3600

Acetone 152052 8004

6 Pregabalin Stage 3

Iso propyl alcohol 162000 7560

7 Dabigetran Iso propyl alcohol 44100 227

Acetone 6897.6 432

8 Verapamil HCL Stage 1

Toluene 249840 9720

Stage 2 Toluene 200880 1800

9 Terfenadine Ethyl acetate 35280 3600




1.1.7 Air Pollution Details

The major air pollution sources from the industry are DG set, boiler and process sections. These sources are provided with stacks of adequate height so as to disperse the emanating flue gases containing SPM, oxides of sulfur and nitrogen without affecting the ground level concentrations and packed column scrubbers are provided to the process sections with adequate stack height as per the regulatory requirements.

The sources of air pollution, type of fuel used, fuel consumption and chimney heights for each of the air pollution sources of the proposed project are indicated in the following table 1.7.

Table 1.7 Sources of air pollution, type of fuel used, APC details

SI. no.

Stack attached to

Fuel used Fuel consumption

Number of stacks

Stack/s height

Air pollution control unit

Predicted emissions

1 Process section

- - 1 15 m ARL

Packed column scrubber – 1 no.

Acid mist/ VOCs

2 Steam boiler –2 Ton capacity – 1 no.s

1 ton capacity 1 no (proposed)

Briquette 163 Kg/hr

82 Kg/hr

1 combined stack

30.48 m AGL

Mechanical dust collector

SO2, NOx, SPM

3 Thermic Fluid Heater (Proposed)

Briquette 75 Kgs/hr 1 10m AGL

Stack SOx, NOx, SPM

4 D.G. set – 250 kVA – 1 no.

15 kVA- 1 no (proposed)

HSD 58.75 L/hr

3 .5 L/hr

1

1

5 m AGL

3m AGL

Stack SOx, NOx, SPM

1.1.8 Noise pollution details The major source of noise pollution in the industry is the DG set for which acoustic enclosure is provided. Also ambient noise levels will be ensured within the ambient standards by inbuilt design of mechanical equipment and building apart from vegetation (tree plantations) along the periphery and at various locations within the industry premises.



1.1.9 Solid waste details The quantity of solid waste generated from the proposed industry is detailed in the following table 1.8.

Table: 1.8 Solid Waste Generation during the Operation Phase

Total no. of employees 50

Assuming per capita solid waste generation rate as 0.25 kg/capita/day

Quantity of solid waste generated 12.5 kg/day

Organic solid waste : 60 % of the total waste 7.5 kg/day

Inorganic solid waste : 40 % of the total waste 5 kg/day

Disposal of domestic solid waste The domestic wastes are segregated at source, collected in bins and composted.

1.1.10 Hazardous Raw Materials Used in the Manufacturing Process

The following raw materials used during the process of manufacture of APIs are hazardous in nature according to Manufacture, Storage and Import of Hazardous Chemical (Amendment) Rules, 19th January 2000, Schedule I, Part II in the table 1.9

Table: 1.9 Hazardous raw materials

Hazardous raw material Sl. No. as per Manufacture, Storage and Import of Hazardous Chemical (Amendment) Rules, 19th January 2000, Schedule I, Part II

Hydrochloric acid 313

Ethanol 248

Sodium Hydroxide 571

Potassium hydroxide 522

Methanol 377

Toluene 628

Iso Propyl Alcohol 334

Formaldehyde 295

Dimethyl Amine 215

Acetone 4

Chloroacetyl Chloride 124

Methylene chloride 400



1.1.11 Hazardous Waste Generation and Its Management during the Manufacturing Process

The hazardous wastes generated during the process of manufacture of different APIs are

stored at hazardous waste storage area and sent to authorize processers. The quantities of

hazardous waste generated from various processes are shown in the following tables 1.10.

1) Solvent Residue and Spent Carbon

Table: 1.10 Quantity of process residue generation from solvent recovery and Carbon

waste generated from manufacturing process

Sl. No.

APIs Quantity of hazardous waste generated, kg/annum

Spent Carbon waste generated, kg/annum

1 Fexofenadine HCl Stage 1

25380 -

Stage 2 23760 -

Stage 3 17820 - 2 Ambroxol HCl

Stage 1 17820 -

Stage 2 18360 1080

3 Amlodipine Besylate 11880 1080

4 Fluconazole stage 1 64260

Stage 2 16200 3240

5 Febuxostat 3468

Stage 2 4404 2244

6 Pregabalin Stage 1 8172 -

Stage 2 16560 -

7 Dabigatran 34200 -

Stage 2 26700 -

8 Verapamil HCl stage 1 38520 -

Stage 2 7200 -

9 Terfenadine 16920 -

Stage 2 18720 -

TOTAL 3,70,344 7,644



Table 1.11 Environmental Management Plan during Operation Phase

Sl. no.

Environmental components

Predicted impacts Probable source of impact Mitigation measures Remarks

1 Ambient air quality

Minor negative impact.

Process of manufacture of APIs

Particulate and gaseous emissions from DG set and boiler

Vehicular Movement

Manufacturing process involves closed operations in various controlled reactors.

The process area is provided with abundant natural light and ventilation and high roofs to disperse the fumes/gases to the outside atmosphere; preventing the increase of ground level concentrations (GLC’S) as it gets dispersed.

Packed column scrubbers are installed to neutralize and control dust and fumes from the process section.

The treated waste gases and fumes will be let out through adequate stack height.

The emissions from DG & boiler will be let out through adequate stacks height

Orderly Movement of Vehicles will done in the premises.

The roads are made of tar and regularly water sprinkling will be done to control fugitive emissions.

DG sets will be used only during power failure.

2 Noise Minor negative impact near noise generation sources inside the premises.

Operation of machineries during the manufacturing process.

Handling and conveying of raw

The conveying system shall be maintained by following routine and periodic maintenance to reduce noise generation in material handling.

-



materials and semi-finished components to different areas of operations

Operation of DG set.

DG set with prebuilt acoustic enclosure as per CPCB norms is installed in dedicated utility area, where the access will be restricted. Also the use of PPE (ear plugs) will be mandatory in this area.

Green belt at the project boundary will act as noise barrier and help in attenuation of noise.

3 Water quality No significant adverse impact

Discharge of and industrial effluent

Domestic sewage treated in septic tank and soak pit.

The industrial effluent is proposed to be treated in an Effluent Treatment Plant (ETP) with Multiple Effect Evaporator (MEE) followed by RO Filtration for treatment, reuse and disposal.

Water conservation measures will be encouraged.

4 Land No negative impact

Discharge of wastewater.

Storage and disposal of solid wastes.

Domestic sewage will be treated in septic and sent to soak pit The industrial effluent is treated in Effluent

Treatment Plant (ETP) with Multiple Effect Evaporator followed by RO Filtration for treatment, reuse and disposal.

-

5 Socio-economic Overall positive impact

Employment opportunities Locally available man power will be utilized to the maximum possible extent.

-



CHAPTER 2

INTRODUCTION OF THE PROJECT/

BACKGROUND INFORMATION 2.1 INTRODUCTION OF PROJECT PROPONENT M/s VPL Chemicals Pvt. Ltd. having registered office at # 27, Behind “The Club” Nayandahalli,

Mysore road, Bangalore have established API’s manufacturing industry at plot no 64,

Sompura Industrial Area, Dabaspet, Nelamangala Taluk, Tumkur Road, Bangalore. Now M/s

VPL Chemicals Pvt. Ltd intend to expand and modify the API’s in the existing facility.

Mr. Patil Shashidhar Gowd S/o Veerana Gowda Patil is aged about 46 years is a young,

dynamic entrepreneur. He is a Post–Graduate (M.Com) and also completed the intermediate

in Chartered Accountants Course (ICAI). He is quite conversant with the corporate financial

matters and corporate laws. Before being taken over the charge of Managing Director of VPL

Chemicals Pvt. Ltd, he has served in many reputed organizations and acquired good

knowledge on financial and management of accounts. He is very conversant with corporate

affairs and travelled widely abroad. Apart from overall corporate matters, personally taking

care of taking care of Accounts & Finances and Human Resources Department.

Mr.Sreedhar G. Patil:

Mr. Shridhar G. Patil S/o Veerana Gowda Patil is aged about 45 years. He has completed his

Master degree (M.Sc. in Chemistry) with 1st Rank and recipient of Gold Medal from Gulbarga

University. With research bent of mind, he joined Indian Institute of Science (IISc), Bangalore,

as Research Scholar. He has secured funding from TEPP from Dept. of Science and Technology

from Govt of India on his independent capacity on the project titled design and development

of Temperature Indicating chalks. Mr. Shridhar could successfully completed the research

project by developing more than 200 formulations and commercialized the developed

technology. He has also developed Temperature Indicating Labels/strips very first time in

India and successfully commercialized the technology. He has also exposed to bulk drugs R &

D and manufacturing processes and travelling widely abroad. Presently he is on the Board of

Directors in VPL Chemicals Pvt. Ltd. His current responsibilities include overall in charge of

Production, Sourcing of raw Materials, Quality Control and R & D departments apart from

rendering technical services to the company.



Dr. Yerriswamy Pateel

Dr. Yerriswamy Pateel S/o Veerana Gowda Patil is aged about 43 years has completed his

Master degree (M.Tech. in Mineral Processing) with 1st Rank and he was recipient of Gold

Medal from Gulbarga University. Acquired Ph.D. Degree on Coal Beneficiation from

Barkatullah (Bhopal) University in the year 2001. He has published more than 25 research

papers in National, International Journals, Conferences, and Seminar proceedings. Before

joining VPL Chemicals Pvt. Ltd, he has served for various institutes and industries. Dr. Pateel

has widely traveled in India and abroad and acquired basic knowledge international

marketing. He is currently one of the Board of Directors of VPL Chemicals Pvt. Ltd. His current

responsibilities include managing of marketing activities and successful commercialization of

the newly developed technologies apart from developing new business alliances. Also taking

care of Quality Assurance Department.

2.2 BRIEF DESCRIPTION ABOUT THE NATURE OF THE PROJECT

M/s VPL Chemicals Pvt. Ltd. Is a private limited company with Shri. Shashidhar G Patil as

Managing Director have already established API’s manufacturing industry at plot no 64,

Sompura Industrial Area, Dabaspet, Nelamangala Taluk, Tumkur Road, Bangalore. Now M/s

VPL Chemicals Pvt. Ltd intend to expand and modify the existing API’s in the existing facility.

An active ingredient (AI) is the substance of a pharmaceutical drug that is biologically active. Terms in similar use include: active pharmaceutical ingredient (API) and bulk active in medicine. Some medications may contain more than one active ingredient. The traditional word for the API is pharmacon or pharmakon which originally denoted a magical substance or drug. A dosage form of a drug is traditionally composed of two things: The API, which is the drug

itself; and an excipient, which is the substance of the tablet, or the liquid the API is suspended

in, or other material that is pharmaceutically inert. Drugs are chosen primarily for their active

ingredients.

2.3 NEED FOR THE PROJECT AND ITS IMPORTANCE TO THE COUNTRY AND/REGION

Bulk drugs have become a part of our life for sustaining many of our day-to-day activities,

preventing and controlling diseases. Bulk drugs manufacturing sector in India is well

established and has recorded a steady growth in the overall Indian industrial scenario. The

bulk drugs and allied industries have been amongst the fastest growing segments of the

Indian industry.

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. It is expected to reach a level of Rs 3200 billion by 2012. It ranks very high in the

third world, in terms of technology, quality and range of medicines manufactured. From

simple headache pills to sophisticated antibiotics and complex cardiac compounds, almost

every type of medicine is now made indigenously.

Playing a key role in promoting and sustaining development in the vital field of medicines,

Indian Pharma Industry boasts of quality producers and many units approved by regulatory

authorities in USA and UK. International companies associated with this sector have

stimulated, assisted and spearheaded this dynamic development in the past years and helped

to put India on the pharmaceutical map of the world.

India's pharmaceutical industry is the third largest in the world in terms of volume. Its rank is

14th in terms of value. India is also one of the top five active pharmaceutical ingredients (API)

producers (with a share of about 6.5 per cent).

The pharmaceutical industry in India meets around 70% of the country's demand for bulk

drugs, drug intermediates, chemicals, tablets, capsules, orals and injectibles. .Between

September 2008 and September 2009, the total turnover of India's pharmaceuticals industry

was US $21.04 billion. The domestic market was worth US $12.26 billion. This was reported

by the Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers. As per a report

by IMS Health India, the Indian pharmaceutical market reached US $10.04 billion in size in July

2010. A highly organized sector, the Indian Pharma Industry is estimated to be worth $4.5

billion, growing at about 8 to 9 percent annually.

The pharmaceutical industry in Karnataka contributes Rs. 350 crore in revenue to the State

exchequer and provides employment for 12,000 people. Its growth rate is between 10-12 per

cent as against the national pharma growth of 12-14 percent. Pharma products worth Rs.

2,000 crore are produced annually, which is 10 per cent of the national production. The

exports sales are Rs.850 crore which is 8 per cent of Indian exports.

International pharma majors have preferred many companies from the State. When large

companies offer their services on contractual basis to global MNCs, they want to outsource

drug production for the domestic market from quality small-medium manufacturers in State.

Here the small-medium units ideally fit into slot as third party manufacturers and serve as

major hubs for pharmaceutical outsourcing. In fact, two of Indian pharma sectors top five

brands, are already outsourced from Karnataka. The units have been recognized for stringent

regulatory enforcement and known to manufacture quality products.

Hence the proponents have proposed to modify and expand the products in the existing facility of the industry at - M/s. VPL Chemicals Pvt. Ltd., at Plot no: 64, Sompura Industrial Area, Dabaspet, Nelamangala Taluk, Tumkur Road, Bangalore.



2.4 DEMANDS‐SUPPLY GAP Based on their informal survey of the market with their current customers and various traders, they have found that there is a big potential for the range of the products they are planning. These products will be an addition to the current range of their products. 2.5 EXPORT POSSIBILITY Depending on the international demand of products they shall export the products. 2.6 DOMESTIC/EXPORT MARKETS Majority of the products will be used for domestic market and some products will be

exported depending on the international market.

2.7 EMPLOYMENT GENERATION (DIRECT AND INDIRECT) DUE TO PROJECT. M/s. VPL Chemicals Pvt. Ltd., will give direct employment to local people based on qualification and requirement. In addition to direct employment, indirect employment shall generate ancillary business to some extent for the local population.



CHAPTER 3

PROJECT DESCRIPTION 3.1 TYPE OF PROJECT The proposed project is expansion/modification of the APIs in the existing facility. The total production capacity 31,000 kg/month.

3.2 LOCATION OF THE INDUSTRY M/s VPL Chemicals Pvt. Ltd., is established at plot no 64, Sompura Industrial Area, Dabaspet, Nelamangala Taluk, Tumkur Road, Bangalore. Google Map Showing Project Site is shown in Fig 3.1

Fig 3.1 Google Map Showing Project Site

933 m above MSL; Latitude: 13°13’'29.51"N; Longitude: 77°15'55.85"E

PROJECT SITE



Fig 3.2 Map showing the Project Site Location on District Map of Bangalore

3.3 BASIS OF SELECTING THE SITE

The efficient functioning of any industry mainly depends on the availability of its basic requirements viz. raw materials, fuel, power, water, manpower etc. The industry is established in Sompura Industrial Area, Dabaspet, Bangalore. The choice of the land confers several advantages, which are summarized below.



1. The site is well connected by roadways. 2. Water will be supplied from Bore well. 3. Power will be supplied from BESCOM. 4. No incidence of cyclones, earthquake, floods or landslides in the region.

3.4 SIZE/MAGNITUDE OF OPERATION The industry “M/s. VPL Chemicals Pvt. Ltd.,” is a small scale industrial unit with a total capital investment of the Expansion project is Eight Lakhs. The total production capacity proposed is 31,000 kg/month. 3.5 PRODUCTS MANUFACTURED The APIs are proposed to be manufactured/Expanded are given in Table no-3.1

Table 3.1: APIs are proposed to be manufactured

Sl. No.

APIs Existing production capacity(Kg/Month)

Production capacity (kg/month)

1 Fexofenadine HCl 100 4500 ( After Expansion)

2 Ambroxol HCl 500 4500 ( After Expansion)


New Products

4500

4 Fluconazole 4500

5 Febuxostat 1000

6 Pregabalin 3000

7 Dabigetran 3000


9 Terfenadine 3000

3.5.1 Manufacturing Process Description Manufacturing process Details of each products is given below

1. FEXOFENADINE HCl 1.1 Process Description

Stage I:

Preparation of Methyl-4{4- [4-(hydroxydiphenylmethyl)-l-piperidinyl}-l-oxobutyl]-α, α-

diphenylmethyl benzene acetate.

Methyl-4-(4-chloro-l-oxobutyryl)-α,α-dimethylρhenyl acetate (Ketone) (meta and para

isomers) [Chloro compound]was dissolved in Methyl Iso butyl Ketone followed by addition of

Azacyclanol and water in presence of Sodium bi carbonate and potassium iodide. Reaction

mixture was refluxed. After the reaction was completed, reaction mixture was cooled to room

temperature and aqueous layer was discarded. Organic layer was filtered and distilled. Add

ethyl acetate cool to room Temp. and filter the material l, i.e., Methyl-4{4- [4-

(hydroxydiphenylmethyl)-l-piperidinyl}-l-oxobutyl]-α, α-diphenylmethyl benzene acetate.



Stage II :

Preparation of Methyl-4{4-r4-(hydroxydiphenylmetyl)-l-piperidinyl}- l-hydroxybutyll-α,α-

dimethyl benzene acetate

The addition of sodium hydroxide in potable water followed by reflux once the reaction

desprotection was completed. The reaction mixture was cooled to room temperature and

slowly cooled cooled to about 0 to 200C followed by addition of sodium boro hydride. At the

same temperature reaction mass stirred for 2 hours. After the reduction was completed the

reaction mass was stirred at room temperature pH of the reaction mass was adjusted to

hydrochloric acid solution. The crystallized mass was stirred at room temperature. The

reaction mixture was centrifuged and dried.

Stage - III:

Preparation of Methyl-4{4-r4-(hydroxydiphenylmetyl)-l-piperidinyl}- l-hydroxybutyll-α,α-

dimethyl benzene acetate to yield crude isomer of Fexofenadine base to Fexofinadine

Hydrochloride (Pure).

Fexofenadine base thus isolated from the above steps was charged to a mixture of methanol

in methyl iso butyl ketone and treated with IPA HCl to make the pH of the solution between

3.0 to 4.0 charcolised, filtered and product is isolated after chilling by centrifuging. The

product is dried at 50 - 60C to a constant weight.



1.2 ROUTE OF SYNTHESIS:

Stage-1

MIBK

Sodium bi carbonate

Azocyclonal

Stage-II

Fexofinadine base

OH

O

NO

OH

O

N

O

OH

OH

OH

N

O

OH

OH

O

NO

OH

O

N

O

OH

CH3 CH3

O CH3

Cl

O

NaOH

Sodium boro hydried

Methanol

HCl



IPA HCL

MIBK , Methanol

Stage-3

Fexofinadine baseFexofinaidine HCL

OH

OH

N

O

OH

ClH

OH

OH

N

O

OH

1.3 FLOW CHART

Stage-1 Chloro Compound RO Water MIBK Sodium Bi Carbonate Potassium Iodide Ethyl Acetate Maintenance at 90-95oC Distillation Crystallization Centrifuge and EA washing Unloading the material (Stage-1)

SS Reactor

SSR-101

1.6 KL

CF-01



Stage-2

Stage-1 Material Caustic Soda Flakes Methanol Sodium Boro Hydride

Temp. Maintenance 65-68oC

pH Adjustment 6.50 to 6.80 Centrifuge and Methanol Washing Unloading the material (Crude)

Stage-3

Stage-2 Material Methanol MIBK

pH Adjustment with IPA HCL

Heating Temp 50oC Hyflow supercell Activated Carbon

Filtration Distillation MIBK Centrifuge Unloading the material (Wet cake) LOD Below 0.5% Drying at 45 to 50oC Unloading the material (Dry)

SS Reactor

CF-

011

SS Reactor

SSR 108

2.0 KL

SS Leaf

Filter

LF-01

GLR

R-107

1.6 KL

CF-

02

TD-02



1.4 Material balance of Fexofenadine HCl

Stage – I

S. No Name of the Input Quantity

in Kg S. No Name of the Out put

Quantity in Kg

1 Methyl-2-[4-(4-Chlorobutanoyl)Phenyl]-2-methyl propionate

0.91 1 Stage-I

1.18

2 Azacyclonol 0.77

2 Operation / Evaporation loss

0.2

3 Purified water 2.27 3 Process water 2.6

Sodium bi carbonate 0.39 Ethyl Acetate 0.98

Potassium Iodide 0.01 Residue 0.47

Ethyl Aceetate 1.08

Total 5.43 Total 5.43

Material balance of Fexofenadine HCl

Stage – II



Quantity in Kg

1 Stage-1 1.18 1 Stagae-II 1.09

2 Sodium boro hydride

0.1

2 Operation / Evaporation loss 0.32

3 Purified Water 0.46 3 Process water 1.2

4 NaoH Flakes 0.22 4 Methanol 3.27

5 HCl 0.73 5 Residue 0.44

6 Methanol 3.63


Material balance of Fexofenadine HCl

Stage – II



Quantity in Kg

1 Stage-1 1.18 1 Stagae-II 1.09

2 Sodium boro hydride 0.1



4 NaoH Flakes 0.22 4 Methanol 3.27

5 HCl 0.73 5 Residue 0.44

6 Methanol 3.63




2. AMBROXOL HCl 2.1 Process Description

Stage –I

2-Amino-3,5-Dibromobenzaldehyde (ADBB) is condensed with trans-4-Aminocyclohexanol in

methanol gives Schiff base material is reduction with sodium borohydride in methanol gives

Ambroxol base in good yield.

Stage – II Ambroxol base is converted into corresponding hydrochloride in acetone by using HCl

followed by filtration gives Ambroxol Hydrochloride


. HCL

Ambroxol base

C13

H18

Br2 N

2O : 378.10

Br

Br

NH2

NH

OHNH2

OH

Br

Br

NH2

O +

Ambroxol base

C13

H18

Br2 N

2O : 378.10

Methanol

Sodium Boro Hydried

Trans 4-Amino cyclohexonol

C6H13NO : 115.18

Stage-I

Stage-II

Br

Br

NH2

NH

OH

Br

Br

NH2

NH

OH

Acetone

HCl

Ambroxol HCl

C14

H18

Br2 N

2OCl : 414.6

2-Amino-3,5-di bromo benzaldehyde

C7H

5Br

2NO : 278.929

AMBROXOL HCL ROS



2.3 FLOW CHART

Stage-1 Trans 4-Amino Cyclohexanol Purified Water 2-Amio-3,5- dibromo benzaldehyde Organic layer Methanol Sodium Boro Hydride

Centrifuge and Methanol Washing Unloading the material (Crude)

SS Reactor

SSR-101

1.6 KL

SS Reactor

CF-

01



Stage-2

Stage-1 Material Acetone

pH Adjustment with HCL


Filtration

Distillation Acetone Centrifuge Unloading the material (Wet cake) LOD Below 0.5% Drying at 45 to 50oC Unloading the material (Dry)

SS Reactor

SSR 108

2.0 KL

CF-

02

TD-02

SS Leaf

Filter

LF-01

GLR

R-107

1.6 KL



2.4 Material balance of Ambroxol HCl

Stage – I

S. No

Name of the Input Quantity

in Kg S.

No Name of the Out

put Quantity

in Kg

1 2-amino-3,5-dibromobenzohydrazide

0.72 1 Stage-1 0.85

2 Trans 4-amino cyclohexnol 0.3 2 Operation / Evaporation loss

0.19

3 Sodium Boro Hydried 0.1 3 Process water 2.72

4 Methanol 4.08 Methanol 3.67

5 Purified water 2.55 Residue 0.32


Material balance of Ambroxol HCl

Stage – II

S. No


in Kg S.

No Name of the Out

put Quantity in

Kg

1 Stage-1 0.85 1 Ambroxol Hcl 1

2 Acetone 6.00 2 Operation / Evaporation loss

0.2

3 Hcl 0.18 3 Acetone 5.52

4 Activated Carbon 0.02 4 Process water 0

5 Hyflow 0.01 5 Resdiue 0.34


http://www.chemicalbook.com/ProductChemicalPropertiesCB41009990_EN.htm

http://www.chemicalbook.com/ProductChemicalPropertiesCB41009990_EN.htm



3. Amlodipine Besylate 3.1 PROCESS DESCRIPTION

Stage-1 Mono methylamine is charged into the reactor and Phathoyl Amlodipine is charged under

stirring at 25 - 30C. The reaction mass is maintained for about 16 hours between 25 and 30°C and Centrifuged. Wet cake is washed with DM water and dried and taken for next stage of processing. Stage-II To Stage-1 material, Benzene Sulphonic acid is added slowly and the mass is maintained for about 3 hours, centrifuged and washed with DM water. The wet material is charged into SS

tray drier. The Material is air dried for 1 hour and then at 60C to 65C with steam. Drying is continued till water content is less than 0.5% w/w. Dried material is unloaded and taken for next stage of purification. Stage III (Purification) The stage II material is taken in a reactor and treated with methanol and charcoal and filtered. The filtrate is distilled to remove methanol and the residue cooled. Ethyl acetate is added to the residue and centrifuged, the mother liquor is collected to recover the ethyl acetate and the wet material is dried. 3.2 ROUTE OF SYNTHESIS

Cl

N+

O

CH3

O

CH3

H

O N

O

O

O CH3

O

Stage-1

CH3 NH2

Phthloyl Amlodipine

M.F :C28H27ClN2O7

M.W :538.98

Mono Methyl Amine

+

Cl

N+

O

CH3

O

CH3

H

O

O CH3

O

NH2

Amlodipine base



Cl

N+

O

CH3

O

CH3

H

O

O CH3

O

NH2

+ S

O

O

OH

Cl

N+

O

CH3

O

CH3

H

O

O CH3

O

NH2

S

O

O

OH

Amlodipine besylate

Stage-2

Cl

N+

O

CH3

O

CH3

H

O

O CH3

O

NH2

+ S

O

O

OH

Cl

N+

O

CH3

O

CH3

H

O

O CH3

O

NH2

S

O

O

OH

Amlodipine besylate

Stage-2



3.3 FLOW CHART Stage-I

MMA

Phthaloyl Amlodipine

Water

To next step

Stage-II

Dried Stage II

SSR

Reactor

Centrifuge ML’s to ETP

Wet material

Drier

Drying

Stage-1

Water

Reactor Stage-I

material

Water + Benzene

Sulphonic acid

Water

Dryer

CF ML’s to ETP



Stage-III Stage-II

Ethyl Acetate

Collect the spent Ethyl Acetate

Wet material

SSR

Reactor

Sparkler

Filter

GLR

Reactor

Drier

Charcoal Methanol

Distill Methanol

Ethyl Acetate

Cool to 0-5°C

Amlodipine Besylate

Miller

Sifter

Blender

CF



3. AMLODIPINE BESYLATE Material balance of Amlodipine besylate

Stage – I

S. No

Name of the Input Quantity in

Kg S.

No Name of the Out

put Quantity in Kg

1 Mono methylamine

2.62 1 Amlodipine base 0.81

2 Phathoyl Amlodipine

1.07 2 Operation / Evaporation loss

0.08



Material balance of Amlodipine besylate

Stage – II

S. No

Name of the Input Quantity in Kg S.

No Name of the Out put Quantity in Kg

1 Amlodipine base 0.81 1 Amlodipine besilate Crude

1.16

2 Benzene sulphonic acid


0.06



Material balance of Amlodipine besylate

Stage – III

S. No

Name of the Input Quantity in Kg S.

No Name of the Out put Quantity in Kg

1 Amlodipine besilate 1.16 1 Amlodipine besilate pure 1

2 Methanol 5.81 2 Methanol 5.75

3 Ethyl acetate 5.81 3 Ethyl acetate 5.79

4 Activated charcoal 0.02 4 Operation / Evaporation loss

0.06

5 Hyflow 0.02 5 Residue 0.22




4. Fluconazole

4.1 Brief Manufacturing Process Stage-1 To di-floro aceto phenone material, 1,2,4 trizole, Toluene and TMSI is added slowly and the mass is maintained for about 4 hours, Adjust pH with KOH flakes and kept under maintenance at 65-68oC,Cool to 5oC and centrifuge, washed with Toluene. The wet material is charged in

to SS tray drier. The Material is air dried for 1 hour and then at 45C to 50C with steam. Drying is continued till LOD content is less than 0.5% w/w. Dried material is unloaded and taken for next stage of purification. Stage 2 The stage I material is taken in a reactor and treated with MDC, Citric acid adjust the pH 3.5 with HCL and charcoal and filtered. The filtrate is distilled to remove MDC and the mother liquor is collected to recover the MDC and the wet material is dried. 4.2 ROUTE OF SYNTHESIS

Stage-I&II

O

N

N

NF

F

NH

N

N

OH

N

N

NF

F

N

N

N

+

2,4-Difluoro-1-(1H-1,2,4 Trizoyl) Aceto phenone

C10H7F2N3O 223.18

1,2,4 Trizole

C3H9IOS 69.06

TMSI

FLUCONAZOLE



4.3 FLOW CHART Stage-1 Difloro Aceto phenone RO Water TMSI Potassium Hydroxide 1,2,4 Triazole Toluene Maintenance at 65-68oC Distillation Crystallization Centrifuge and Toluene washing Unloading the material

SS Reactor

CF-01



Stage-II

Stage-1 Material Citric acid MDC

pH Adjustment with HCL(CP Grade)


Filtration Distillation MDC Centrifuge Unloading the material (Wet cake) LOD Below 0.5% Drying at 45 to 50oC Unloading the material (Dry)

SS Reactor

CF

TD

SS Leaf

Filter

GLR



Material balance of Fluconazole

Stage – I

S. No


in Kg S. No

Name of the Out put

Quantity in Kg

1 1,2,4 Triazole 0.52 1 Fluconazole(Crude) 1.16

2 Potassium Hydroxide

0.75 2 Toluene 0.34

3 Tri methyl sulfoxonium Iodide

0.52 3 Process water 3.48

4 Di floro acetone phenone


0.08

5 Toluene 0.39 5 Residue 1.19

6 Purified Water 2.9 6 0


Material balance of Fluconazole

Stage – II

S. No


in Kg S. No

Name of the Out put

Quantity in Kg

1 Fluconazole(Crude) 1.16 1 Fluconazole(Pure) 1.00

2 CP HCL 0.83 2 MDC 1.40

3 MDC 1.56 3 Process water 0.90

4 Citric acid 0.03 4 Operation / Evaporation loss

0.06

5 Carbon 0.06 5 Residue 0.30

6 Hyflow 0.02




5. Febuxostat

5.1 Process Description: Stage-I:

Ethyl-2-(3-cyano-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylate (NV07-3) is

hydrolyzed with sodium hydroxide solution in isopropyl alcohol to furnish the product. The

pH is adjusted with hydrochloric acid and solid is separated by filtration as Febuxostat

crude.

Stage-II

Febuxostat (crude) is dissolved in acetone and charcolised. After filtration, acetone is

distilled out and solid is filtered to give Febuxostat.

5.2 Route of Synthesis:

Ethyl-2-(3-Cyano-4-isobutoxyphenyl)-4- IPA, NaOH, HCl Febuxostat Crude methyl-5-thiazolecarboxylate M.Wt.=344.428 Stage II – Purification of Febuxostat

H 3C H O

H 3C

H O S O Acetone S

H 3C O O

N

H 3C O

C H 3

C H 3 N

N Febuxostat Crude N Febuxostat

M.Wt=316.37



5.3 Process Flow chart:

STAGE –1: NV07-3 Purified Water Sodium hydroxide Hydrochloric acid Isopropyl alcohol Maintenance Temp. Distillation Crystallization Centrifuge and EA washing Unloading the material (Stage-1)

Purification:

Stage-I Crude Acetone

Temp. Maintenance

Centrifuge and Acetone Washing Unloading the material (Pure)

SS Reactor

1.6 KL

CF

SS Reactor

103

CF



5.4 MATERIAL BALANCE

Material balance of FEBUXOSTAT

Stage – I

S. No


in Kg S.

No Name of the Out

put Quantity

in Kg

1

Ethyl-2-(3-cyano-4-isobutoxyphenyl)-4- methyl-5-thiazolecarboxylate 1.528

1 Stage-1 1.299

2 Sodium hydroxide 0.231


3 Con. Hydrochloric acid 0.624

3 Process water 34.864

4 Isopropyl alcohol 6.005

Isopropyl alcohol 5.705

5 Water 34.009

Residue 0.289


Material balance of FEBUXOSTAT

Stage – II

S. No


in Kg S.

No Name of the Out

put Quantity

in Kg

1

Febuxostat crude 1.299

1 FEBUXOSTAT 1

2

Acetone 13.338


3

Activated carbon 0.065

3 Acetone

12.671

4

Celite 0.057

4 Spent Carbon

0.187

5

5 Residue (Org. + Carbon) 0.367




6. Pregabalin

6.1 PROCESS DESCRIPTION Stage-I (+)-3-(Carbamoy methyl)-5-methyl hexanoic acid (Di Acid) react with R(+) Phenyl Ethyl amine in the presence of Chloroform to get the product R-(-)-3-(Carbamoylmethyl)-5-methylhexanoic acid Stage-II R-(-)-3-(Carbamoylmethyl)-5-methylhexanoic acid react with Bromine in the presence of alkaline condition by using sodium hydroxide in the presence of chloroform and purified water to get pregabalin technical Stage-III The product of Pregabalin, the technical grade, dissolved with Iso propyl alcohol at temperature 80-85oC and filtered the reaction mass. Then cool to 0-5oC then filter in Centrifuge to get Pregabalin pharma

6.2 ROUTE OF SYNTHESIS Stage-I

NH2

OCH3

CH3

OH O

CH3 NH2

R-(+)-1-Phenyl ethyl amine salt ofR-(-)-3-(Carbamoylmethyl)-5-methylhexanoic acid

NH2

OCH3

CH3

OH O

HCl

NaOH

Stage-II

NH2

OCH3

CH3

OH O

CH3

CH3

OH O

NH2

NaoCl

(

R-(-)-3-(Carbamoylmethyl)-5-methylhexanoic acid S-(+)-3- Amino methyl)-5-methyl hexanoic acid (Tech) C9H17NO3 : 187.24 C8H17NO2 : 159.226



Stage-III

CH3

CH3

OH O

NH2

CH3

CH3

OH O

NH2

IPA

Water

6.3 FLOW CHART Stage-I CMH Acid Chloroform Sodium Hydroxide R(+) Phenyl ethyl hexanoic acid HCL Maintenance at 35oC Crystallization Cf. and Chloroform washing Unloading the material

SS Reactor

4.0 KL

CF-01



Stage-II

Stage-2 Material NaOH Flakes Bromine DM water


Cool to 10oC

Centrifuge and DM Washing Unloading the material (Technical)

SS Reactor

2.0 KL

CF-

01



Stage-III

Stage-III Material Iso Propyl alcohol

Heating to temp 50oC

Cool to 0oC to 5oC Hyflow supercell Activated Carbon

Filtration Distillation IPA Centrifuge Unloading the material (Wet cake) LOD Below 0.5% Drying at 45 to 50oC Unloading the material (Dry)

SS Reactor

2.0 KL

CF-

02

TD-02

SS Leaf

Filter

LF-01

GLR

2.0 KL



Material balance of Pregabalin

Stage – I

S. No


Kg

S. No

Name of the Out put Quantity in

Kg

1

(±)-3- (Carbamoylmethyl)-5-methylhexanoic acid (CMH Acid)

3.64 1 Stage-I 1.42

2 R(+) Phenyl Ethyl amine

1.86 2

(±)-3- (Carbamoylmethyl)-5-methylhexanoic acid (CMH Acid)

2.22

3 Chloroform 43.69 3 R(+) Phenyl Ethyl amine

1.79

4 Methanol 0.72 4 Chloroform 42.44

5 NaOH 0.27 5 Operation / Evaporation loss

0.14

6 HCL 0.97 6 Process water 1.14 7 Purified Water 0.27 7 Residue 2.27



Stage – II

S. No

Name of the Input Quantity in Kg

S. No

Name of the Out put Quantity in Kg

1

R-(-)-3-(Carbamoylmethyl)-5-methylhexanoic acid

1.68

1 Pregabalin (Crude) 1.18

2 NaoH flakes 1.1 2 Process Water 7.25

3 Bromine

1.3

3 Operation / Evaporation loss

1.84

4 Purified water 4.3 4 Residue 0.46

5 HCl 2.36 5 0 Total 10.73 Total 10.73


Stage – III

S. No


Kg

S. No

Name of the Out put Quantity in Kg

1 Pregabalin (Crude) 1.18 1 Pregabalin (Pure) 1

2 Iso propyl Alcohol 4.71 2 Iso propyl Alcohol 4.5

3 Purified Water 4.71 3 Water 4.57

4 Hyflow 0.06 4 Operation / Evaporation loss

0.09

5 Organic Residue 0.5




7. Dabigetran

7.1 Process Description:

Stage-I:

The propanoic acid methyl ester derivate of formulae-I is dissolved in IPA and acetic acid,

hydrogenated with damp Pd/C at RT at 2 bar hydrogen pressure. After completion of the

reaction the catalyst is filtered off and dissolved in IPA was added to filtrate. To get formulae-

II precipitated out which was filtered off and dried.

Stage-II:

The Tosylate salt obtained in the stage I was dissolved in acetone and the mixture is combined

with hexyl chloroformate in presence of potassium hydroxide at temperature 15oC. After

completion of the reaction the precipitated product is filtered off and washed with acetone

mixture. The resulting crude is crystallized with water. Schematic diagram of Dabigatran is

shown below and material balance for Dabigatran is presented below

7.2 Route of synthesis: Stage-I CH CH

3

N3 N O

O

N NH

CO2

O N NH O H2,Pd,C,IPA,ACOH

N HN

NH

O N NH

O N 2

PTSA,

O N

M. Wt 44.01

O N

M. Wt: 499.56

M. Wt: 541.56

[ I ] [ II ]

Stage-II

CH3 Acetone/ CH

3 O O

C6 H13

N NH

KOH N KCl

O HN

Mol. Wt.: 56.11 O N M. Wt: 36.46

O N NH2 Hexa chloro formate O N

N HN NH

N 2 H2O

O N M.Wt.164.63 O N

M. Wt: 499.56 Dabigetran (Pharma) Mol. Wt.: 18.02

[ II ]

M. Wt: 627.73



7.3 Process Flow chart:

STAGE –1: Propionic acid ethyl ester (KSM) Purified Water

Acetic acid IPA P-toulene sulphonic acid Maintenance Temp. Distillation Crystallization Centrifuge Unloading the material (Stage-1)

Purification: Stage-I Crude

Potassium hydroxide Acetone Hexa chlorofomate

Temp. Maintenance

Centrifuge and Acetone Washing Unloading the material (Pure)

SS Reactor

1.6 KL

CF

SS Reactor

103

CF



9.4 MATERIAL BALANCE

Material balance of Dabigetran Stage – I

S. No

Name of the Input Quantity in Kg Output

Quantity in Kg

Remarks

1 3-[(1-Methyl-2-{[4-(5-oxo-4,5-dihydro- [1,2,4]oxadiazol-3-yl)-phenylamino]-methyl)-1H benzoimidazole-5- carbonyl)-pyridin-2-yl- amino]-propionic acid ethyl ester

0.0485 Stage-1 product 0.0423 To stage-2

2 P-toluene sulphonic acid

0.0125 Carbon dioxide 0.0037 let out in atmosphere safely

3 Acetic acid 0.01 Solvents

4 IPA 1.25 IPA 0.7121

IPA recovered 1.225 Recovered & Reused

IPA loss 0.0063 Fugitive loss

IPA residue 0.0188 Solvent in residue

3-[(1-Methyl-2-{[4-(5-oxo- 4,5-dihydro- [1,2,4]oxadiazol-3-yl)- phenylamino]-methyl)-1H benzoimidazole-5- carbonyl)-pyridin-2-yl- amino]-propionic acid

ethyl ester

0.0024 Organic residue



Acetic acid 0.01 Organic residue

Total Input 1.321 Total out put 1.321



Material balance of Dabigetran

Stage – II

S. No

Name of the Input Quantity in Kg

Output

Quantity in Kg

Remarks

1 Stage I Product 0.0423 Dabigetran 0.05 Final Product

2 Hexa chlorofomate 0.014 Potassium chloride

0.0063 To Wastewater

3 Acetone 0.6 Water formed in reaction


4 Potassium Hydroxide

0.0048 Acetone recovered

0.5748 Recovered & Reused

5 Hydrochloric acid 0.00019 Acetone loss 0.0036 Fugitive loss

6 Water 0.5 Acetone to Wastewater


Acetone residue 0.0168 Solvent in residue

Organics

Stage I Product 0.0025 Organic residue

Hexa chlorofomate


Water 0.5001 To Waste water

Total Input 1.1612 Total out put 1.1612



8. Verapamil HCl 8.1 PROCESS DESCRIPTION Stage 1: 2-(3,4-dimethoxyphenyl)-3-methylbutanenitrile is condensed with N-(3-chloropropyl)-N-[2-(3,4-dimethoxyphenyl) ethyl]-N-methylamine in presence of sodamide, nitrogen and toluene. Methanol is added to neutralize sodamide and later on with water. The solvent is separated and used directly for next step. Stage 2 Verapamil base in toluene is treated with activated carbon, filtered and the filtrate is treated with HCl to give a precipitate of verapamil HCl, which is filtered, washed with toluene.

8.2 ROUTE OF SYNTHESIS

Scheme: Stage-I

Stage-II

HCl



8.3 FLOW CHART

Stage-I

2-(3,4-dimethoxyphenyl)-3- methylbutanenitrile Sodamide, N2 N-(3-chloropropyl)-N-[2- Reactor (3,4-dimethoxyphenyl) ethyl]-N-methylamine Toluene

Methanol, water Organic layer

Filter

Filtrate

Next step Material Balance



Filtrate

Centrifuge

Verapamil HCl

Stage-II Verapamil base in toluene Activated carbon Reactor

Filter HCl Wash with toluene

Material balance of Verapamil HCl

Stage – I

S. No


Kg

S. No

Name of the Out put Quantity in

Kg

1 2-(3,4-dimethoxyphenyl)-3-methylbutanenitrile

1.08 1 Verapamil base 1.32

2 N-(3-chloropropyl)-N-[2-(3,4-dimethoxy phenyl) ethyl]-N-methylamine

0.75 2 Toluene 6.94

3 Sodamide 0.16 3 Operation / Evaporation loss 1.98

4 Toluene 7.21 4 Process water 4.07 5 Methanol 2.68 5 Process Residue 1.07 6 Purified Water 3.5 0


Material balance of Verapamil HCl

Stage – II

S. No Name of the Input Quantity in

Kg S. No Name of the Out put

Quantity in Kg

1 Verapamil base 1.32 1 Verapamil HCl 1.00

2 Toluene 5.62 2 Toluene 5.58

3 HCl 0.61 3 Operation / Evaporation loss 0.06

4 Activated carbon 0.01 4 Process water 0.74

5 Hyflow 0.02 5 Residue 0.20




9. Terfenadine 9.1 Process Description

Stage – I

1-(4-tert-butyl phenyl)-4-chloro-1-butanone was dissolved in Methyl Iso butyl Ketone

followed by addition of Azacyclonol and water in presence of Sodium bi carbonate and

potassium iodide. Reaction mixture was refluxed for about 36 hours. After the reaction was

completed, reaction mixture was cooled to 80oC charging by purified water. The reaction

mixture was stirred at same temp. for 30 min, there after allowed the mass to settle and

separate aqueous layer. Organic layer was distilled under reduced pressure and degassed for

2 hours to get the oily mass. Known volume of water and Ethyl acetate was added to the

reaction mixture at the same temperature and stirred for 2 hours at 5oC, the product was

filtered and washed with Ethyl acetate, i.e., 1-(4-tert-butylphenyl)-4-{4-

[hydroxyl(diphenyl)methyl]piperidin-1-yl}butan-1-one

Stage – II

Stage-I 1-(4-tert-butylphenyl)-4-{4-[hydroxyl(diphenyl)methyl]piperidin-1-yl}butan-1-one

was added to a mixture of methanol. The reaction mixture was cooled to 10°C and a solution

of sodium boro hydride was added. The reaction mixture was stirred at room temperature

for 4 hours and monitored by TLC. After the reduction was completed the solution was heated

to 60°C and the pH was adjusted to neutral by adding with dilute hydrochloric acid The

reaction mixture was again heated to reflux for about 2 hour and cooled to 5° C, the product

was filtered and washed with water and methanol. The material was dried. i.e., Terfenadine.


TERFENADINE ROUTE OF SYNTHESIS Stage-1

CH3CH3

Cl

O

CH3

NH

OH

OH

O

N+

1-(4-tert-butyl phenyl)-4-chloro-1-butanone

M.F C14

H19

CLO2

M.Wt. 238.75

1-(4-tert-butylphenyl)-4-{4-[hydeoxy(diphenyl)methyl]piperidin-1-yl}butan-1-one

M.F: C32

H39

NO2 :M.Wt. 469.658

Azocyclonol

M.F. C18H21NO, M.Wt : 267.365

MIBK,NaHCO3

KI



Stage-2

1-[4-(1,1-Dimethylethyl)phenyl]-4-[4-(hydroxydiphenylmethyl)piperidin-1-yl]buta

n-1-ol.

M.F. C32

H41

NO2 : M.Wt 471.7

OH

O

N

OH

OH

N

SBH

Methanol

1-(4-tert-butylphenyl]-4-[4-(hydroxy(diphenyl)methyl]piperidin-1-yl]butan-1-ol.

M.F. C32

H39

NO2 : M.Wt 469.658

9.3 FLOW CHART

STAGE –1:

TR Chloro Compound Purified Water MIBK Sodium Bi Carbonate Potassium Iodide Ethyl Acetate Maintenance Temp. Distillation Crystallization Centrifuge and EA washing Unloading the material (Stage-1)

SS Reactor

1.6 KL

CF



Stage-2

Stage-1 Material Sodium Boro Hydried Methanol


pH Adjustment 6.50 to 6.80 Centrifuge and Methanol Washing Unloading the material (Crude)

Purification:

Stage-II Crude Methanol


Cool to 5oC Centrifuge and Methanol Washing Unloading the material (Pure)

SS Reactor

103

CF

SS Reactor

103

CF



Material balance of Terfenadine

Stage – I


Kg S. No

Name of the Out put

Quantity in Kg

1 1-(4-tert-butylphenyl)-4-chloro-1-butanone

0.91

1

Stage-I 1.18

2 Azacyclonol 0.77 2

Operation / Evaporation loss

0.2

3 Purified water 2.27 3 Process water 2.6 4 Sodium bi carbonate 0.39 Ethyl Aceate 0.98 5 Potassium Iodide 0.01 Residue 0.47 6 Ethyl Aceetate 1.08


Material balance of Terfenadine

Stage – II


Kg S. No

Name of the Out put

Quantity in Kg

1 Stage-1 1.18 1 Stagae-II 1 2 Sodium boro hydride

0.1 2 Operation /

Evaporation loss 0.45 3 HCl 0.46 3 Methanol 4.26 4 Methanol 4.49 4 Residue 0.52




3.6 RAW MATERIALS The raw materials required for the manufacture of APIs are appended in the table 3.2 below. Raw materials as listed will be procured as per the production requirement.

Table -3.2 Raw Materials Requirement for manufacture of API Sl.

No. Product Raw materials Quantity required Solvents

required after recycling

kg/annum

kg/batch kg/month kg/annum

1 Fexofenadine HCL

Methyl (Stage1) 273 4095 49140 -

Azacylonol 231 3465 41580 -

Potassium iodide 3 45 540 -

Sodium bi carbonate

117 1755 21060 -

Sodium Boro hydride

30 450 5400 -

Sodium hydroxide flakes

66 990 11880 -

HCL 300 3285 39420 -

methyl iso butyl ketone

1092 16380 196560 -

Hyflow 3 45 540 -

Activated Carbon 3 45 540 -

Purified water(stage 1)

681 10215 122580 -

Stage 2 138 2070 24840 -

Methanol(stage 2)

1089 16335 196020 19440

Stage 3 165 2475 29700 2700

Ethyl acetate 324 4860 58320 5400

Iso propyl alcohol 165 2475 29700 2700

2 Ambroxol HCL 2-amino-3,5-Dibromo Benzaldehyde

216 3240 38880 -

Trans 4-aminocyclohexnol

90 1350 16200 -

Sodium Borohydride

30 450 5400 -

Activated carbon 6 90 1080 -

Hy flow 3 45 540 -

HCL 54 810 9720 -

Purified water 765 11475 137700 -

Acetone 1800 27000 324000 25920

Methanol (Stage I)

1224 18360 220320 22140



3 Amlodipine besylate

Monomethylamine

786 11790 141480 -

Phathoylamlodipine

321 4815 57780 -

Benzene sulphonic acid

129 1935 23220 -

Activated charcoal

6 90 1080 -

Hy flow supercell 6 90 1080 -

Purified water (stage 1)

621 9315 111780 -

Stage 2 735 11025 132300 -

Methanol 1743 26145 313740 3240

Ethyl acetate 1743 26145 313740 1080

4 fluconazole Di-floro-tetra-aceto-phenone

348 5220 62640

Trimethyl solfoxonium iodide

156 2340 28080

1,2,4 triazole 156 2340 28080

Potassium hydroxide

225 3375 40500

HCL 249 3735 44820


Citric acid 9 135 1620


Toulene 117 1755 21060 2700

5 Febuxostat Ethyl-2-(3-cyano-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylate

153 1530 18360

Febuxostat crude 130 1300 15600

NAOH 23 230 2760

HCL 62 620 7440

Acetone 1333.8 13338 160056 8004



Celite 6 60 720

Water 3401 34010 408120



6 Pregabalin R-(-)-3- carbamoymethyl hexanoic acid

504 5040 60480

Hydrochloric acid 708 7080 84960

Sodium Hydroxide

330 3300 39600



7 Dabigetran 3-[(1-Methyl-2-{[4-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)- phenylamino]-methyl)-1H benzoimidazole-5- carbonyl)-pyridin-2-yl-amino]-propionic acid ethyl ester

15 150 1800


4 40 480

Acetic acid 3 30 360

IPA 375 3750 45000

Hexa chlorofomate

4 40 480

Acetone 180 1800 21600

Potassium Hydroxide

2 20 240

Hydrochloric acid

0.1 10 120

Water 150 1500 18000

8 Verapamil HCL 2-(3,4- Dimethoxyphenyl)-3-methylbutanenitrile

324 3240 38880

N-(3-choloropropyl)-N-[2-(3,4-dimethoxyphenyl)ethyl]-N-methylamine

225 2250 27000

Sodamide 48 480 5760



HCL 183 1830 21960



Toluene (stage 1 ) 2163 21630 259560 9740

Stage 2 1686 16860 202320 1440

RO water 1050 10500 126000

Methanol 804 8040 96480

9 Terfenadine 1-(4-tert-butyl phenyl)-4-chloro-1-butanone

273 2730 32760

Azacyclanol 231 2310 27720

Potassium Iodide 3 30 360

Sodium bi carbonate

117 1170 14040

Sodium boro hydride

30 300 3600

HCL 138 1380 16560


Methanol 1347 13470 161640 3600

Ethyl Acetate 324 3240 38880 8280

3.6.1 STORAGE FACILITY FOR RAW MATERIALS AND PRODUCTS Adequate storage facilities are provided for the raw materials, products etc. the details of

Storage Facilities is given in Table-3.3

Table 3.3:- Details of Storage Facilities

Sl. No. Storage Facility for Facility

1 Raw Materials Warehouse 2 Products Bonded finished goods store 3 Industrial Effluent Effluent treatment Plant with Multiple Effective

Evaporator (MEE) followed by RO filtration with adequate storage tanks

4 Hazardous Waste In organic Process residue and organic waste from process is collected in HDPE Bags and sent to PCB authorized Processers for land filling Spent carbon is collected in HDPE Bags and sent to PCB authorized Processers for land filling Used Containers after detoxification will be sold to authorized agents.



3.6.2 MACHINERY & EQUIPMENT DETAILS The detailed list of machinery & equipments in the industry are appended in the tables 3.4 below

Location: Pharma Block

Table 3.4 List of Major Production Equipment

Location: Intermediate Block

Sl. No.

Name of the Equipment Identification Number

MOC Capacity

1. Glass Lined Reactor R-107 GLR 1.6 KL 2. SS Reactor R-106 SS 316 2.0 KL 3. Leaf Filters LF-01 SS 316 100 L 4. Nutsche Filter NF-02 SS 316 500 L 5. Centrifuge CF-02 SS 316 36” 6. Tray Dryer TD-02 SS 316 48 Trays 7. Multi Mill MM-01 SS 316 100 Kg / Hr 8. Double Cone Blender B-01 SS 316 500 L 9. Sifter SF-01 SS 316 30” 10 Pulveriser PUL-01 SS 316 50 Kg / Hr

Sl. No.

Name of the Equipment

Identification Number

MOC Capacity

1. Glass Lined Reactor R-104 GLR 3.0 KL 2. Glass Lined Reactor R-102 GLR 1.6 KL 3. Glass Lined Reactor R-109 GLR 3.0 KL 4. SS Reactor R-105 SS 316 3.0 KL 5. SS Reactor R-103 SS 316 2.0 KL 6. SS Reactor R-101 SS 316 1.6 KL 7. SS Reactor R-108 SS 316 2.0 KL 8. SS Receivers REC-01 SS 316 500 L 9. SS Receivers REC-02 SS 316 500 L

10. SS Receivers REC-03 SS 316 500 L 11. SS Addition Tanks AT-01 SS 316 500 L 12. SS Addition Tanks AT-02 SS 316 500 L 13. SS Addition Tanks AT-03 SS 316 500 L

14. FRP Addition Tanks AT-04 FRP 500 L

15. Leaf Filter LF-101 SS 316 100 L

16. Nutsche Filter NF-101 SS 316 500 L

17. Centrifuge CF-101 SS 316 48”

18. Tray Dryer TD-101 SS 316 48 Trays



Location: Pilot Block

Table-3.4a. List of Major Utilities

S.No Name of the equipment Capacity Qty (Nos)

1 Brine Chiller (-20 Deg C) 20TR 1

2 Boiler 2 Tons/hr 1

3 Cooling tower 80TR 1

4 Cooling tower 200TR 1

5 RO plant 3KL/hr 1

6 High Vacuum pump (oil ring type) 2TR 1

7 High Vacuum Pump (Jet type) 40TR 2

8 Solvent storage tanks 15KL 2

9 Air Compressor (110ltrs) 100Psi 1

10 DG set 250KVA 1

11 Acid storage (HCl) tank (PP/FRP) 10KL 1

12 Scrubber 2000CFM 1

13 Multiple Effect Evaporator 600ltr/hr 1

Table- 3.4b List of major laboratory Equipments

Sl. No.

Name of the Equipment

Identification Number

MOC Capacity

1. All Glass Assembly PB-01 Borosil 25L




Sl. No.

Name of the Equipment Identification Number

Make & Model

1. Analytical Balance VPL/QC/AB 001 Contech, CA – 214

2. Analytical Semi MircoBalance

VPL/QC/AB 002 Radwag, Model No. AS 60/220.R2

3. KF Titrator VPL/QC/KF 001 Galaxy Scientific Equipments 4. KF Titrator VPL/QC/KF 002 Polmon Instruments MI 453 5. Melting Point Apparatus VPL/QC/MP 001 DBK Instruments 6. TLC View Chamber VPL/QC/TV 001 Galaxy Scientific Equipments 7. Hot Air Oven VPL/QC/OV 001 Galaxy Scientific Equipments 8. Vacuum Oven VPL/QC/VO 001 Multispan UTC 113P 9. Muffle Furnace VPL/QC/MF 001 Bio – Technics India, 774

10. pH Meter VPL/QC/PH 001 Henna : HI 2215 11. pH Meter VPL/QC/PH 002 Galaxy Scientific Equipments SV4 12. HPLC VPL/QC/LC 001 Shimadzu, LC-2010

13. HPLC VPL/QC/LC 002 Waters, Alliance. 2695 14. Gas Chromatography VPL/QC/GC 001 Shimadzu, GC-2014, C11484506286

with Head space Tekmar

15. Ultrasonic Sonic cleaner VPL/QC/SC 001 Ultrasonic Sonic



3.7 RESOURCE OPTIMIZATION/RECYCLING AND RE-USE ENVISAGED IN THE PROJECT 3.7.1 Solvent Recovery & Re-Use Various solvents are proposed to be used during the manufacturing process. The solvents

proposed to be recovered and recycled during the process of recovering the solvent of such

product are detailed in table 3.5 below.

Table 3.5 Solvent Recovery

Sl.No

Product Raw materials Quantity (kg/annum)

Recovered and recycled

Lost

1 Fexofenadine HCL Stage 1



Stage 3 Iso propyl alcohol 27000 2700

Methanol 27000 2700

Methyl iso butyl ketone

186840 9720

2 Ambroxol HCL Stage 1

Methanol 198180 22140

Stage 2 Acetone 298080 25920

3 Amlodipine besylate Stage 3

Methanol 310500 3240


4 fluconazole Toluene 18360 2700

5 Febuxostat Iso propyl alcohol 68460 3600

Acetone 152052 8004

6 Pregabalin Stage 3

Iso propyl alcohol 162000 7560

7 Dabigetran Iso propyl alcohol 44100 227

Acetone 6897.6 432

8 Verapamil HCL Stage 1

Toluene 249840 9720

Stage 2 Toluene 200880 1800

9 Terfenadine Ethyl acetate 35280 3600


Note: * The solvent lost during the process of solvent distillation is mainly due to organic thermal disintegration and in form of residue left behind from the bottom un-distilled product. Evaporation loss is minimized by the passage of chilled water through the condenser.

16. UV-spectrophotometer VPL/QC/UV 001 Shnmadzu : UV 1601

17. Stability Chambers VPL/QC/STB 001 ADITI Associate

18. Stability Chambers VPL/QC/STB 002 MAK Pharma

19. Stability Chambers VPL/QC/STB 003 MAK Pharma

20. Potentiometer VPL/QC/AT 001 Spectra Lab Model No. AT38-C



3.7.2 SOLVENT RECOVERY SYSTEM 1. Solvent to be recovered is transferred in to a closed, Jacketed, Vertical, cylindrical and

agitated reactor.

2. Control measure for reactor, are Temperature, Pressure and speed of agitator.

3. Reactor Jacket has all the utility connections.

4. Vapor line connected to primary condenser, where in the cooling water is circulated.

(Cooling water has the multi pass facility to achieve better heat transfer and counter flow).

5. The system has an additional facility of reflux system.

6. The condensed liquid from primary condenser will flow to secondary condenser by

gravity, where in chilled water is circulated for further sub cooling of recovered solvent.

7. The vent of primary condenser is connected again to the same secondary condenser with

necessary control valve system. In total secondary condenser acts like sub cooler and as

well as vent cooler.

8. The measure control for both condenser and sub cooler are pressure and temperature

both on tube side and on shell side.

9. The sub cooled solvent then flows and collects in 2 receivers, where in further cooling is

made by circulating the chilled brine. The measure control for both receiver is the

temperature and pressure in shell as well as in Jacket.

10. The vent is always from the receiver to the wet scrubber or the vacuum pump.

3.8 HAZARDOUS RAW MATERIALS USED IN THE MANUFACTURING PROCESS The following raw materials used during the process of manufacture of APIs are hazardous in nature according to Manufacture, Storage and Import of Hazardous Chemical (Amendment) Rules, 19th January 2000, Schedule I, Part II in the table 3.6

Table: 3.6 Hazardous raw materials

Hazardous raw material Sl. No. as per Manufacture, Storage and Import of Hazardous Chemical (Amendment) Rules, 19th January 2000, Schedule I, Part II

Hydrochloric acid 313

Ethanol 248

Sodium Hydroxide 571

Potassium hydroxide 522

Methanol 377

Toluene 628

Iso Propyl Alcohol 334

Formaldehyde 295

Dimethyl Amine 215

Acetone 4

Chloroacetyl Chloride 124

Methylene chloride 400



3.8.1 Hazardous waste generation and its management during the manufacturing process

The hazardous wastes generated during the process of manufacture of different APIs are

stored at hazardous waste storage area and sent to authorize processers. The quantities of

hazardous waste generated from various processes are shown in the Table- 3.7.

1. Solvent residue/ Spent Carbon

Table: 3.7 Quantity of process residue generation from solvent recovery and Carbon waste

generated from manufacturing process

Sl. No.

APIs Quantity of hazardous waste generated, kg/annum

Spent Carbon waste generated, kg/annum

1 Fexofenadine HCl Stage 1

25380 -

Stage 2 23760 -

Stage 3 17820 - 2 Ambroxol HCl

Stage 1 17820 -

Stage 2 18360 1080

3 Amlodipine Besylate 11880 1080

4 Fluconazole stage 1 64260

Stage 2 16200 3240

5 Febuxostat 3468

Stage 2 4404 2244

6 Pregabalin Stage 1 8172 -

Stage 2 16560 -

7 Dabigatran 34200 -

Stage 2 26700 -

8 Verapamil HCl stage 1 38520 -

Stage 2 7200 -

9 Terfenadine 16920 -

Stage 2 18720 -

TOTAL 3,70,344 7,644



3.8.2 Hazardous Waste Quantity and Disposal Details

Table 3.8 Hazardous Waste Quantity and Disposal Details

Sl. no

Hazardous waste Quantity kg/annum

Disposal Details

1 Residue from the manufacturing process

3,70,344 In organic Process residue and organic waste from process is collected in HDPE Bags and sent to PCB authorized Processers for land filling

2 Spent Carbon 7,644 Spent carbon is collected in HDPE Bags and sent to PCB authorized Processers for land filling 3 Waste oil

generation from DG set

200 Collected and sent to authorized reprocessors

4 Inorganic salt from MEE.

52,800 Spent carbon is collected in HDPE Bags and sent to PCB authorized Processers for land filling 5 Used Containers 12 kg Used Containers after detoxification will be sold to authorized agents.

3.9 DOMESTIC SOLID WASTE RE-USE

The total quantity of domestic wastes generated is about 12.5 kg/day which will be segregated at source, collected in bins and composted. The composted waste will be used as manure for landscape development.

3.10 WATER, ENERGY/POWER REQUIREMENT & SOURCE

3.10.1 Water

The water demand is met from Bore well water supply. The requirement of water for the unit is for domestic, industrial purposes. Details are appended in section 3.11.1 later in the report.

3.10.2 Power

The total power requirement of the industry is 150 kVA. Further two diesel generator of 250 kVA and 15 kVA capacity is installed to serve as an alternative source of power supply to this unit.



3.11 WASTES GENERATED & SCHEME FOR THEIR MANAGEMENT/DISPOSAL

3.11.1 Water demand and wastewater/effluent discharge

Source of water supply: Bore well Total number of employees: 50 people

Per capita water demand: 40 LPCD

The total quantity of water required for the industry is about 6 KLD. The break-up of the consumption of water is as presented below.

Table 3.9: Water Consumption and Discharge

Water consumed for Consumption (LPD)

Discharge (LPD)

(a) Domestic (toilet, canteen etc.) 2000 1800

(b) Gardening/Landscape development 350 -

(c) Industrial purpose

Process

1. RO plant and its reject 7200-5513=1687 (reject)

8873 (process effluent + Rejects)

a. Process consumption 5513

2. Washing/Cleaning 1500 1500

3. Boiler feed for 2 MT boiler 3000 100 (Blow down)+ DM reject 600 a. DM plant/rejects 600

4. Cooling tower – 2 nos. 1000-800 (Condensate)= 200

(make up water)

20

5. Scrubber – 1 no. 500 500

6. R & D 150 150

Total 16300 13543 or say 13600KLD

At any given time only one product will be manufactured Note: LPD – liter per day; KLD – kilo liter per day *Start up water requirement for industrial purpose is 13950. After recycling of Evaporator condensate the fresh water requirement will be 4000 LPD. Therefore the total fresh water requirement for the project is 6.5 KLD. The treatment methods and the final disposal of each type of wastewater generated is

appended in the table 3.10 below



Table 3.10: Sewage/effluent treatment and discharge

Sewage/effluent generated from

Treatment units provided Final disposal point

(a) Domestic Treated in Septic tank Disposed to Soak pit

(b) Industrial Collection tanks of 10 KL capacity (4 No.s) are provided.

Industrial effluent is proposed to be treated in Effluent Treatment Plant with Multiple Effect Evaporator (MEE) followed by RO filtration for treatment, reuse and disposal.

3.12 Product wise water consumption and discharge

Table 3.11: Product-wise water consumption for process and effluent discharge

Sl.NO

Products Water consumption

(L/batch)

Effluent discharge (L/batch)

No. of batches /month

Total water consumption

(L/month)

Total effluent

discharge (L/month)

1 Fexofenadine HCL

819 1140 15 12285 17100

2 Ambroxol HCL 765 816 15 11475 12240


1355.65 2202 15 20334.75 33030

4 Fluconazole 870 1314 15 13050 19710 5 Febuxostat 3401 3486 10 34010 34860 6 Pregabalin 2784 3888 10 27840 38880 7 Dabigatran 150 151 10 1500 1510 8 Verapamil 1050 1443 10 10500 14430 9 Terfenadine 681 780 10 6810 7880

Total 1,37,804.75 1,79,640

Note:

Considering no. of working days/month = 25 1. Daily water consumption from process

= 1,37,804.75/25 = 5512.19 or say 5513 LPD 2. Daily effluent discharge from the process

= 179640/25= 7185.6 or say 7186 LPD 3. Daily effluent discharge from the washings/Cleaning

= 37500/25 = 1500 LPD



3.12.1 Waste Water Characteristics Table 3.12 Waste Water Characteristics

3.12.2 Treatment Scheme for Industry Waste water

Sl.No Characteristics

Units Values

1. pH Mg/L 6.20-6.50

2. Total Dissolved Solids Mg/L 10,500-19,500

3. Total Suspended solids Mg/L 130-180

4. Chemical Oxygen Demand Mg/L 1000-1800

5. Biological oxygen Demand Mg/L 1600-3000

6. Chlorides as Cl Mg/L <500

7 Sulphates as SO4 Mg/L <1500

8. Oil & Grease Mg/L <1.00

11743 LPD

Screening

Neutralization

tank

Clarifier Tank

Feed

Tank

Condensate

9982 LPD

(85%)

Inorganic

Residue

176 Kg

Loss

235 LPD

MEE



Water Balance Chart

LANDSCAPING 350 LPD

BOREWELL WATER SUPPLY

Cooling Tower bleed off 20 LPD

WATER CONSUMPTION- 6318 LPD or 6.5 KLD

DOMESTIC WATER DEMAND 2000 LPD

Scrubber

500 LPD Boiler consumption 3600-2700=900 LPD

Cooling tower Make - up water 200 LPD (1000-800 return)

Washing/ Cleaning

1,500 LPD

Scrubber effluent 500 LPD

INDUSTRIAL WATER DEMAND- 13950 LPD- Start up requirement Daily requirement after recycling from Evaporator Condensate:

13950 – 9982 = 3968 LPD or say 4KLD

RO water Plant

7200 LPD

Process consumption

5,513LPD

Domestic wastewater

1800 LPD

R&D

150 LPD

R&D effluent 150 LPD

DM tank 900 LPD

Boiler blow down

100 LPD + DM reject 600

* Process effluent & RO

rejects 8873 LPD

Washing effluent

1,500 LPD

12 KLD will be sent to Effluent Treatment Plant with Multiple Effect Evaporator followed by RO for Reuse

Loss 180 LPD

Septic tank Soak pit

Condensate, 2700



3.13 Air Pollution Details The major air pollution sources from the industry are DG set, boiler and process sections. These sources are provided with stacks of adequate height so as to disperse the emanating flue gases containing SPM, oxides of sulfur and nitrogen without affecting the ground level concentrations and packed column scrubbers are provided to the process sections with adequate stack height as per the regulatory requirements.

The sources of air pollution, type of fuel used, fuel consumption and chimney heights for each of the air pollution sources of the project are indicated in the following table 3.13.

Table-3.13 Air Pollution Sources and Control

SI. no.

Stack attached to

Fuel used Fuel consumption

Number of

stacks

Stack/s height

Air pollution control unit

Predicted emissions

1 Process section

- - 1 15 m ARL

Packed column scrubber – 1 no.

Acid mist/ VOCs

2 Steam boiler –2 Ton capacity – 1 no.s

1 ton capacity 1 no (proposed)

Briquette 334.81 Kg/hr

167.47 Kg/hr

1 30.48 m AGL

Mechanical dust collector

SO2, NOx, SPM

3 D.G. set – 250 kVA – 1 no.

15 kVA- 1 no (Proposed)

HSD 58.75 L/hr

3 .5 L/hr

1 5 m AGL

3m AGL

Stack SOx, NOx, SPM

4 Thermic Fluid Heater (Proposed)

Briquette 75 Kgs/hr 1 10 m AGL

Stack SOx, NOx, SPM

3.13.1 Scrubbing System Details

Evacuation 750M3/Hr at Room temperature Acid Fume Capacity 25 Kg/Hr Scrubbing Media Caustic Solution/Chilled water MOC PP+FRP, body made of 3mm PP and 5mm FRP Pickings 12mm Honeycomb packing in PVC Operating Temperature Ess than 350C Blower Capacity 750M3/Hr, 2 HP Motor



3.4 Scrubbing System

3.14 Noise pollution details The major source of noise pollution in the industry is the DG set for which acoustic enclosure is provided. Also ambient noise levels will be ensured within the ambient standards by inbuilt design of mechanical equipment and building apart from vegetation (tree plantations) along the periphery and at various locations within the industry premises. 3.15 Solid waste details The quantity of solid waste generated from the proposed industry is detailed in the following table 3.14.

Table: 3.14 Solid Waste Generation during the Operation Phase

Total no. of employees 50

Assuming per capita solid waste generation rate as 0.25 kg/capita/day

Quantity of solid waste generated 12.5 kg/day

Organic solid waste : 60 % of the total waste 7.5 kg/day

Inorganic solid waste : 40 % of the total waste 5 kg/day

Disposal of domestic solid waste The domestic wastes are segregated at source, collected in bins and composted.



3.16 SCHEMATIC REPRESENTATIONS OF THE FEASIBILITY DRAWING

A schematic representation of the overall feasibility and environmental assessment process is shown in Figure 3.6.

Fig 3.6: Feasibility & environmental assessment process

Significant

Not

economic

Feasibility study conducted for newly proposed industry

Statement of intent by proponent

Guidelines for EIA by SEAC/MoEF

Abandon project

Determine the coverage of the EIA - scoping

Describe the environment – baseline study

Describe the project

Identify the impacts

Evaluate the impacts

Mitigation

Preventive measures

Prepare draft EIS

FINAL EIA REPORT

CONSIDER ALL PHASES OF PROJECT –

CONSTRUCTION, DEVELOPMENT, INSTALLATION &

FINAL OPERATION/ PRODUCTION

SO

CIO

-ECO

NO

MIC

ISSU

ES

MO

NIT

OR R

EVIE

W



4.1 SITE CONNECTIVITY

Table-4.1 Connectivity to Project Site

Sl. No.

Road Distance from the project site (km)

Direction w.r.t. project site

1 NH 207 1.4 North west

2 NH-4 1.7 South west

3 Dabaspet Railway station 2 North west

4 Tumkur 20 South west

5 Kempegowda International Airport, Bangalore

48 East

Fig- 4.1 Google Map Showing Connectivity to Project Site

Note: All distances mentioned are aerial.

CHAPTER 4

SITE ANALYSIS

Dabaspet

railway station



4.2 LAND FORM, LAND USE & OWNERSHIP M/s. VPL Chemicals Pvt. Ltd., is an Active Pharmaceutical Ingredients (APIs), manufacturing

industry already established at Plot No. 64, Sompura Industrial Area, Dabaspet, Nelamangala

Taluk, Tumkur Road, Bangalore. Now the proponents intend to expand and modify the

products in the existing facility.

4.3 TOPOGRAPHY

M/s. VPL Chemicals Pvt.Ltd., is located at latitude of 13°13'29.51"N & longitude

77°15'55.85"E at an elevation of 933 m above MSL. The topo map showing the location of the

project site is appended as fig 4.2.

Fig-4.2 Topo Map

Project Site



4.4 EXISTING LAND USE PATTERN Table 4.2 Existing Land Use Pattern

Sl. No.

Particulars Details Distance from the project site

(km)

Direction w.r.t. project site

1 Agriculture Minor activities - scattered Beyond industrial area

-

2 National park, forest

Bannerghatta national park

60 km South east

3 Water bodies Hosahalli lake 1.89 km South

Note: a) All distances mentioned are aerial. b) The project is a notified by KIADB, Karnataka Govt. industrial area.

4.5 EXISTING INFRASTRUCTURE

The list of existing infrastructure at the project site is 1. Water supply from Bore well 2. Power supply will be from BESCOM 3. Storm water drainage system is provided

4.6 SOIL CLASSIFICATION The soils of Bangalore Rural districts are broadly classified in to four categories viz (i). Loamy

soil (ii) Lateritic soil (iii) Lateritic gravelly soil and (iv) Red sandy soil. Red loamy soils generally

occur on hilly to undulating land slope on granite and granite gneisses. Lateritic soil occurs in

undulating terrain forming plain to gently sloping topography of peninsular gneiss region.

Lateritic gravelly soils occur in upland regions of lateritic soils, Red sandy soil occurs in

undulating land slopes. These soils are derived from acidic rocks granites and granitic gneiss.



4.7 CLIMATIC DATA FROM SECONDARY SOURCES

Table 4.3: Meteorological Data of Bangalore for the Year 2015 Mont

h Temperature

0C Relative

humidity % Precipitation

rate (mm/hr)

Atmospheric pressure (mb)

Wind speed (m/s)

Inversion / mixing height

(m)

Cloud cover

(tenths)

Min Max Max Min Min Max Min Max Min Max Day Night Min Max

Jan 12.4 25.6 84.8 58.3 0 1.27 909 919 0 6.7 2303 2477 2 10

Feb 13.1 28.9 76.9 44.8 0 1.52 908 915 0 5.1 2517 1786 2 5

Mar 16.4 29.5 69 38.8 0 1.02 907 917 0 6.2 2798 2057 2 6

Apr 18.2 30.8 76.7 50.7 0 3.81 908 914 0 5.1 2910 1799 2 5

May 18.5 32 82.7 61.0 0 2.54 905 913 0 6.2 3319 2317 2 5

June 17.9 30.9 88.6 71.7 0 4.83 904 913 0 10.3 2828 4000 2 10

July 17.4 29.4 89 75.5 0 3.81 904 912 0 8.7 2691 3638 2 10

Aug 17 28.5 88.9 74.5 0 4.06 904 912 0 7.2 2678 2779 3 10

Sept 17.2 29.5 91.4 75.3 0 2.29 905 912 0 7.2 2802 2801 2 10

Oct 16.8 28.8 88.5 73.5 0 2.03 904 913 0 5.7 2575 2046 3 10

Nov 16.8 25.9 93.5 78.1 0 3.81 905 915 0 6.2 2177 2247 2 10

Dec 11.8 24.4 87.6 66.8 0 1.52 906 914 0 6.7 1756 2522 2 10

4.7.1 Temperature The mean maximum temperature is observed at (32°C) in the month of May and the mean

minimum temperature at (11.8°C) is observed in the month of December. In the summer

season the mean minimum temperature is observed during the month of March (16.4°C).

During the monsoon the mean maximum temperature is observed to be 30.9°C in the month

of June with the mean minimum temperature at 17°C during August. By the end of September

with the onset of post monsoon season (October - November), day temperatures drop

slightly with the mean maximum temperature at 28.8°C in October and mean minimum

temperature is observed at 16.8°C for both October & November. The values are presented

in table 4.3.

4.7.2 Relative Humidity

Minimum and maximum values of relative humidity have been recorded. The minimum

humidity is observed to be at 38.8% in the month of March and the maximum is 91.4% in the

month of September. The mean minimum values of humidity during summer, monsoon, post-

monsoon and rainy seasons are 38.8%, 71.7%, 73.5% & 44.8% during the months of March,

June, October and February respectively. Similarly the maximum values are 82.7%, 91.4%,

93.5%, 87.6% in the months of May, September, November & December during the summer,

monsoon and post monsoon & winter seasons. The values are presented in table 4.3.



4.7.3 Rainfall

The monsoon in this region usually occurs twice in a year i.e. from June to September and

from October to November. The maximum annual rate of precipitation over this region ranges

between 1.02 to 4.83 mm/hr.

4.7.4 Atmospheric Pressure

The maximum and the minimum atmospheric pressures are recorded during all seasons. In

the summer season, the mean maximum and minimum pressure values are observed to be

917 mb in the month of March and 905 mb in the month of May respectively. During monsoon

season, the maximum pressure is 913 mb and minimum 904 mb. The maximum pressure

during the post-monsoon season is observed to be 915 mb in November and minimum

pressure is 904 mb in the month of October. During the winter season the minimum

atmospheric pressure is 906 mb in December and the maximum is 919 mb in the month of

January. The values are presented in table 4.3.

4.7.5 Inversion Height

The maximum inversion heights at the project site during the day time & night time for all the

months of the year is as given in the table 3.1. The maximum mixing height of 4000 m is

observed during the month of June during the night time and 3319 m during the month of

May during the day time. The minimum inversion heights are 1756 m in the month of

December during the day and 1786 m during the night in the month of February.

4.7.6 Cloud cover

The minimum cover measured in the unit of tenths is 2 and the maximum observed cloud

cover is 10.

4.7.7 Wind

The data on wind patterns are pictorially represented by means of wind rose diagrams for the entire year as figure 4.3 (for different seasons).

Predominant wind directions

Season Period Wind direction Summer March to May North West

Monsoon June to September East

Post monsoon October to November South West

Winter December to February North West



4.8 SOCIAL INFRASTRUCTURE

Infrastructure is the basic physical and organizational structures needed for the operation of

a society or enterprise or the services and facilities necessary for an economy to function.

The term typically refers to the technical structures that support a society, such as roads,

water supply, sewers, electrical grids, telecommunications and so forth and can be defined as

"the physical components of interrelated systems providing commodities and services

essential to enable, sustain or enhance societal living conditions”.

Viewed functionally, infrastructure facilitates the production of goods and services and also

the distribution of finished products to markets, as well as basic social services such as schools

and hospitals; for example, roads enable the transport of raw materials to a factory.

Table -4.4 List of Infrastructural Facilities in the Surroundings

Sl. No.

Hospital Distance from the industry

Direction w.r.t. the industry

1 Nelamangala General Hospital 19.8 South East

2 Harsha Hospital 18.8 South East

3 Manipal Hospital 20.2 North West

4 Nidavanda Govt.high school 10 South east

5 Nidavanda Railway Station 2.3 North East

6 Bangalore City Railway Station 43 South East

7 Kempegowda International Airport 48 East

Note: All distances mentioned are aerial.



Fig 4.3: Wind Rose Diagrams

1. March to May (summer season)



2. June to September (monsoon season)



3. October to November (post monsoon season)



4. December to February (winter season)



CHAPTER 5

PLANNING BRIEF

5.1 PLANNING CONCEPT M/s. VPL Chemicals Pvt. Ltd., is an Active Pharmaceutical Ingredients (APIs) manufacturing industry. It is the expansion and modification project. The expansion and modification of the API’s will be done in the existing facility. 5.2 POPULATION PROJECTION The expansion and modification will be done in existing facility no construction activity is envisaged Total no. of people employed during operation phase: 50 people 5.3 LAND-USE PLANNING The land use planning is given in Table 5.1

Table 5.1: Land-Use Pattern

Sl. No. Particulars Area (SQM) In %

1 Total plot area 4856.23 100%

2 Hard paved area 926.23 20%

3 Landscape/Green-belt area 1500 30%

4 Built-up area 2430 50%

5.4 ASSESSMENT OF INFRASTRUCTURE DEMAND 1. National highway 207 is at 1.4 Km from project site

2. National highway 4 which connects Bangalore – Pune is at distance 1.7 km from project

site

3. The project is in designated industrial area internal roads in the industrial area and

project site is already available.



5.4.1 Water supply & sewerage infrastructure Water demand for the industry is from Bore well. The domestic sewage generated is treated in septic tank and sent to soak pit. The industrial wastewater is treated in Effluent treatment Plant (ETP) with MEE followed by RO filtration for treatment, reuse and disposal. 5.5 AMENITIES/FACILITIES Proper site services such as with Drinking water, safety equipments & first Aid is provided to

the workers.



CHAPTER 6

PROPOSED INFRASTRUCTURE

6.1 INDUSTRIAL AREA (PROCESSING AREA) M/s. VPL Chemicals Pvt. Ltd., is an Active Pharmaceutical Ingredients (APIs) manufacturing industry. The expansion and modification of the API’s will be done in the existing facility. 6.2 RESIDENTIAL AREA (NON PROCESSING AREA) The non-processing area is green belt and open area.

6.3 GREEN-BELT An area of 1500 Sq.m of total plot area is green-belt/landscape development. About 50 trees of various native/indigenous variety are already planted. Another 50 trees are proposed in the expansion project 6.4 SOCIAL INFRASTRUCTURE Details Given in Chapter- 4, section 4.8 6.5 CONNECTIVITY The site is well connected with roadways. NH-207 & NH-4 which is about 1.4 km & 1.7 km

respectively.

6.6 SEWERAGE SYSTEM Sewage pipes are laid in entire company for the removal and disposal of mainly non harmful

liquid wastes from the offices and domestic waste, these liquid wastes are sent to septic tank

& soak pit.

6.7 INDUSTRIAL WASTE MANAGEMENT The industrial wastewater is treated in Effluent Treatment Plant with Multiple Effect Evaporator followed by RO filtration for treatment, reuse and disposal.



6.8 SOLID WASTE MANAGEMENT The domestic garbage is composted within the industry premises & the product will be used as manure for green-belt/landscape development. Hazardous solid waste will be stored in HDPE bags and sent to authorize reprocessors. 6.9 POWER REQUIREMENT & SUPPLY SOURCE The total power requirement of the industry is 150 kVA which is sourced from BESCOM.

Further two diesel generator of 250 kVA & 15 kVA capacity is installed to serve as an

alternative source of power supply to this unit.



CHAPTER 7

REHABILITATION & RESETTLEMENT

PLAN

M/s VPL Chemicals Pvt. Ltd. is in a designated industrial area. The expansion and

modification will be in the existing facility. No home outstees/land outstees are expected &

hence no rehabilitation plan is envisaged.



CHAPTER 8

PROJECT SCHEDULE & COST

ESTIMATES 8.1 TIME SCHEDULE The time schedule for completion of the proposed project is given in the following table

Particulars Time schedule

Start of construction activity Existing plant

Completion Existing facility

8.2 ESTIMATED PROJECT COST Total capital investment on the proposed Project is detailed as under

Sl.No. Details In lakhs

1 Investment on Plant and machinery 5

2 Environment Management Budget 3

TOTAL 8

Eight Lakhs only



CHAPTER – 9

ANALYSIS OF PROPOSAL

Observing the demographic pattern of the study area it can be inferred that occupational pattern is a mixture more of agriculture rather industrial. The proposed project will increase the employment potential by creating direct and in-direct employment opportunities and thus be beneficial for the local and nearby populace The management of the industry gives preference to local people with both direct and indirect employment.

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