JSP Form I - environmentclearance.nic.in · 2 APPENDIX I (See paragraph - 6) FORM 1 (I) Basic...

1

FORM-1

For

PROPOSED OF BULK DRUGS AND BULK DRUG

INTERMEDIATES MANUFACTURING UNIT

of

M/s. KRUFREN PHARMA

PLOT NO. C/251(251/2), GIDC, SAYKHA,

TAL: VAGRA, DIST: BHARUCH-392130 (GUJ.)

NABL Accredited Testing Laboratory

ISO 9001:2008 Certified Company

Aqua-Air Environmental Engineers P. Ltd.

403, Centre Point, Nr. Kadiwala School, Ring

Road, Surat - 395002

Prepared By:











Prepared By:

2

APPENDIX I

(See paragraph - 6)

FORM 1

(I) Basic Information

Sr.

No.

Item Details

1. Name of the project/s M/s. KRUFREN PHARMA

2. S. No. in the schedule 5(f)

3. Proposed capacity/ area/ length/ tonnage

to be handled/ command area/ lease

area/ number of wells to be drilled

For detail Please refer Annexure – I

4. New/Expansion/Modernization New

5. Existing Capacity/Area etc. Proposed Capacity: 149 MT/Month

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? If

yes, please specify.

No

9. Location

Plot/Survey/Khasra No. Plot No: C/251(251/2)

Village Saykha

Tehsil Vagra

District Bharuch

State Gujarat

10. Nearest railway station/airport along with

distance in kms.

Nearest Railway Station: Bharuch = 30 kms

Nearest Airport: Surat = 70 kms

11. Nearest Town, city, District Headquarters

along with distance in kms.

Nearest town: Bharuch = 30 kms,

Nearest District Head quarter: Bharuch =

30 km

12. Village Panchayats, Zilla Parishad,

Municipal Corporation, local body

(complete postal address with telephone

nos. to be given)

Vill: Saykha, Tal: Vagra, Dist: Bharuch,

Gujarat.

13. Name of the applicant M/s. KRUFREN PHARMA

14. Registered Address Plot No: C/251(251/2), GIDC, Saykha, Tal:

Vagra, Dist: Bharuch-392130 (Guj.).

15. Address for correspondence: M/s. KRUFREN PHARMA Plot No: C/251(251/2), GIDC, Saykha, Tal:

Vagra, Dist: Bharuch-392130 (Guj.).

Name Mr. Kantilal L. Patel

Designation (Owner/Partner/Director) Partner

3

Address B/201, Nilkanth Palace, GIDC, Ankleshwar-

393002, Dist: Bharuch (Guj.)

Pin Code 393002

e-mail [email protected]

Telephone No. +919998144307

Fax No. -

16. Details of Alternative Sites examined, if

any.

Location of these sites should be shown

on a topo sheet.

NA

17. Interlinked Projects NA

18. Whether separate application of

interlinked project has been submitted?

NA

19. If yes, date of submission NA

20. If no, reason NA

21. Whether the proposal involves

approval/clearance under: if yes, details of

the same and their status to be given.

(a) The Forest (Conservation) Act, 1980?

(b) The Wildlife (Protection) Act, 1972?

(c) The C.R.Z. Notification, 1991?

No

22. Whether there is any Government

Order/Policy relevant/relating to the site?

No

23. Forest land involved (hectares) NA

24. Whether there is any litigation pending

against the project and/or land in which

the project is propose 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.

NA

• 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.).

4

(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.)

Sr.

No.

Information/Checklist confirmation Yes/

No

Details thereof with approximate

quantities frates, wherever possible)

with source of information data

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

No --

1.2 Clearance of existing land, vegetation

and Buildings?

Yes Minor site clearance activities shall be

carried out to clear shrubs and weed.

1.3 Creation of new land uses? No --

1.4 Pre-construction investigations e.g.

bore Houses, soil testing?

No

1.5 Construction works? Yes For detail Please refer Annexure – II

1.6 Demolition works? No There will not any demolition work at the site.

1.7 Temporary sites used for construction

works or housing of construction

workers?

No --

1.8 Above ground buildings, structures or

earthworks including linear structures,

cut and fill or excavations

Yes For detail Please refer Annexure – II

1.9 Underground works mining or

tunneling?

No --

1.10 Reclamation works? No --

1.11 Dredging? No --

1.12 Off shore structures? No --

1.13 Production and manufacturing

processes?

Yes For detail Please refer Annexure -III

1.14 Facilities for storage of goods or

materials?

Yes Dedicated storage area for storage of Raw Materials and finished products, solvents, etc. shall be provided.

1.15 Facilities for treatment or disposal of

solid waste or liquid effluents?

Yes Facilities for treatment or disposal of liquid effluents are given as Annexure – V & Facilities for treatment or disposal of solid waste is given as Annexure –VI.

1.16 Facilities for long term housing of

operational workers?

No The unit shall be running round the clock. The operational staff will be recruited locally and working in shift, hence no housing for the operational workers.

1.17 New road, rail or sea traffic during

Construction or Operation?

No There will not be any new road/rail or sea traffic during construction or operational phase.

1.18 New road, rail, air waterborne or other No --

5

transport infrastructure including new

or altered routes and stations, ports,

airports etc?

1.19 Closure or diversion of existing

transport routes or infrastructure

leading to changes in traffic

movements?

No --

1.20 New or diverted transmission lines or

Pipelines?

No --

1.21 Impoundment, damming, culverting,

realignment or other changes to the

hydrology of watercourses or aquifers?

No --

1.22 Stream crossings? No --

1.23 Abstraction or transfers of water form

ground or surface waters?

Yes Water Source: GIDC Water Supply

1.24 Changes in water bodies or the land

surface Affecting drainage or run-off?

No --

1.25 Transport of personnel or materials for

construction, operation or

decommissioning?

Yes By road only.

1.26 Long-term dismantling or

decommissioning or restoration works?

No --

1.27 Ongoing activity during

decommissioning which could have an

impact on the environment?

No --

1.28 Influx of people to an area either

temporarily or permanently?

No --

1.29 Introduction of alien species?

No --

1.30 Loss of native species or genetic

diversity?

No --

1.31 Any other actions? No --

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

Sr.

No.

Information/checklist confirmation Yes/

No

Details there of (with approximate

quantities frates, wherever possible) with

source of information data

2.1 Land especially undeveloped or

agricultural land (ha)

No The land is for Industrial Use

2.2 Water (expected source & competing

users) unit: KLD

Yes Water Source: GIDC Water Supply

Water balance is given as Annexure – IV

6

2.3 Minerals (MT) No --

2.4 Construction material - stone,

aggregates,

and / soil (expected source - MT)

Yes Construction materials, like steel, cement,

crushed stones, sand, rubble, etc.

required for the project shall be procured

from the local market of the region.

2.5 Forests and timber (source - MT) No. --

2.6 Energy including electricity and fuels

(source, competing users) Unit: fuel

(MT), energy (MW)

Yes Power required from DGVCL is

Proposed = 100 KVA

D. G. Set : Proposed = 100 KVA

Fuel

Proposed

Briquettes of Bio-Coal/Coal: 1900

MT/day

HSD: 50 Lit/Day

2.7 Any other natural resources (use

appropriate standard units)

No --

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.

Sr.

No.


No


quantities/rates, wherever possible) with


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 For details please refer Annexure – VIII

3.2 Changes in occurrence of disease or

affect disease vectors (e.g. insect or

water borne diseases)

No --

3.3 Affect the welfare of people e.g. by

changing living conditions?

No --

3.4 Vulnerable groups of people who could

be affected by the project e.g. hospital

patients, children, the elderly etc.

No --

3.5 Any other causes No --

7

4. Production of solid wastes during construction or operation or decommissioning (MT/month)

Sr.

No.


No




4.1 Spoil, overburden or mine wastes

No --

4.2 Municipal waste (domestic and or

commercial wastes)

No --

4.3 Hazardous wastes (as per Hazardous

Waste Management Rules)

Yes Please refer Annexure –VI

4.4 Other industrial process wastes

No --

4.5 Surplus product

No --

4.6 Sewage sludge or other sludge from

effluent treatment

Yes

Please refer Annexure – VI

4.7 Construction or demolition wastes

No Construction waste shall be utilized for

leveling & land filling in the premises.

4.8 Redundant machinery or equipment

No --

4.9 Contaminated soils or other materials

No --

4.10 Agricultural wastes

No --

4.11 Other solid wastes Yes Please refer Annexure –VI

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

Sr.

No.


No


quantities/rates, wherever possible)


5.1 Emissions from combustion of fossil

fuels from stationary or mobile

sources

Yes For details Please refer Annexure – VII.

5.2 Emissions from production processes

Yes Stack emission will remain within the

norms prescribed by CPCB. Please refer

Annexure – VII.

5.3 Emissions from materials handling

storage or transport

Yes The construction materials such as stones,

cements, bricks & coal may pollute the air by

8

dust particles. But it will be controlled by

covering the trucks & trailers by clothes during

transportation.

5.4 Emissions from construction activities

including plant and equipment

Yes During construction work, the Nearby

buildings area will be covered by sheets or

clothes to avoid dust Contamination in air.

5.5 Dust or odors from handling of

materials including construction

materials, sewage and waste

No --

5.6 Emissions from incineration of waste No --

5.7 Emissions from burning of waste in

open air (e.g. slash materials,

construction debris)

No --

5.8 Emissions from any other sources No --

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

Sr.

No.


No



with source of information data with


6.1 From operation of equipment e.g.

engines, ventilation plant, crushers

Yes The Noise level will be within the

prescribed limit. Adequate preventive &

control measures will be taken at noisy

area. No significant noise, vibration or

emission of light & heat from the unit.

6.2 From industrial or similar processes No All machinery / equipment shall be well

maintained, shall have proper.

Foundation with anti-vibrating pads

wherever applicable to keep noise levels

within permissible limits.

Acoustic enclosures shall be provided for

DG set.

6.3 From construction or demolition No --

6.4 From blasting or piling No --

6.5 From construction or operational

traffic

No --

6.6 From lighting or cooling systems No --

6.7 From any other sources No --

9

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

Sr.

No.


No




7.1 From handling, storage, use or spillage

of hazardous materials

Yes For detail please refer Annexure – VIII

7.2 From discharge of sewage or other

effluents to water or the land

(expected mode and place of

discharge)

No --

7.3 By deposition of pollutants emitted to

air into and or into water

No --

7.4 From any other sources No --

7.5 Is there a risk of long term build up of

pollutants in the environment from

these sources?

No --

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

Sr.

No.


No




8.1 From explosions, spillages, fires, etc.

from storage, handling, use or

production of hazardous substances

Yes For detail please refer Annexure – VIII

8.2 From any other causes No --

8.3 Could the project be affected by

natural disasters causing

environmental damage (e.g. floods,

earthquakes, landslides, cloudburst

etc)?

No --

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

Sr. No.

Information/Checklist confirmation

Yes/ No




9.1 Lead to development of supporting. lities, ancillary development or development stimulated by the

Yes For detail please refer Annexure – IX

10

(II) Environmental Sensitivity

Sr.

No.

Areas Name/

Identity

Aerial distance (within 15km.)

Proposed project location boundary

1 Areas protected under international

conventions, national or local legislation for

their ecological, landscape, cultural or other

related value

Yes Site is located in Saykha Industrial Area,

Saykha, Tal. Vagra, Dist. Bharuch,

Gujarat.

2 Areas which important for are or sensitive

Ecol logical reasons - Wetlands,

watercourses or other water bodies, coastal

zone, biospheres, mountains, forests


Saykha, Dist. Bharuch, Gujarat. Forest

area of Rajpipla is 100 kms away.

3 Area used by protected, important or

sensitive Species of flora or fauna for

breeding, nesting, foraging, resting, over

wintering, migration


Saykha, Tal. Vagra, Dist. Bharuch,

Gujarat.

4 Inland, coastal, marine or underground

waters

Yes Narmada River: 10 km (approx.) away

from Project Site

5 State, National boundaries No N.A.

6 Routes or facilities used by the public for

access to recreation or other tourist, pilgrim

areas

No Public transportation

7 Defense installations No N.A.

8 Densely populated or built-up area No Bharuch City: 5.24 lakh population.

9 Area occupied by sensitive man-made land

uses Hospitals, schools, places of worship,

community facilities)

No N.A.

project which could have impact on the environment e.g. • Supporting infrastructure (roads, power supply, waste or waste water treatment, etc.)

• housing development • extractive industry • supply industry • other

9.2 Lead to after-use of the site, which

could have an impact on the

environment

No --

9.3 Set a precedent for later

developments

No --

9.4 Have cumulative effects due to

proximity to other existing or

planned projects with similar effects

No --

11

10 Areas containing important, high quality or

scarce resources (ground water resources,

surface resources, forestry, agriculture,

fisheries, tourism, minerals)

No The project being in industrial area

does not affect agricultural land.

11 Areas already subjected to pollution

environmental damage. (those where

existing legal environmental standards are

exceeded)

No Site is located in Saykha Industrial

Area, Saykha, Tal. Vagra, Dist.

Bharuch, Gujarat.

12 Are as susceptible to natural hazard which

could cause the project to present

environmental problems (earthquake,

subsidence, landslides, flooding erosion, or

extreme or adverse climatic conditions)

No N.A.

IV). Proposed Terms of Reference for EIA studies: For detail please refer Annexure – X.

I hereby give undertaking 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 given, if any, to the project will be revoked at our risk and cost.

Date: 14/2/2019

Place: Saykha

Stamp and Signature of the Applicant

12

LIST OF ANNEXURES

SR. NO. NAME OF ANNEXURE Page No.

I List of Products with their Production Capacity 13

II Layout Map of the Plant 23

III Brief Manufacturing Process Description 24

IV Details of Water Consumption & Waste water Generation 86

V Details of Treatment Scheme and Disposal 88

VI Details of Hazardous /Solid Waste Generation, Handling and Disposal 92

VII Details of Stack and Vent 94

VIII Details of Hazardous Chemical Storage & Handling 95

IX Socio-Economic Impacts 96

X Proposed Terms of Reference for EIA studies 97

XI Toposheet 99

XII GIDC Plot Allotment Letter 100

XIII GIDC Waster Supply Letter 101

XIV TSDF Membership Certificate 102

13

ANNEXURE-I

LIST OF PRODUCTS WITH THEIR PRODUCTION CAPACITY

SR.

NO. NAME OF THE PRODUCTS CAS NO.

QUANTITY

MT/MONTH END-USE OF PRODUCT

1 NABIVILOL 152520-56-4 1 Beta-blocker

2 ZONISAMIDE 68291-97-4 10 Anti depression

3 FLUCONAZOLE 86386-73-4 10 Antifungal medication

4 LORATADINE 79794-75-5 1 Anti depression

5 GLIMEPRIDE 93479-97-1 1 anti diabetic

6 AMIODARONE

HYDROCHLORIDE 1951-25-3 10 irregular heartbeats

7 CILOSTAZOL 73963-72-1 10 intermittent claudication

8 APRIPITANT 170729-80-3 10 antiemetic

9 SEVELAMER HYDROCHLORIDE 152751-57-0 10 a noncalcemic phosphate

binder

10 NICARDIPINE

HYDROCHLORIDE 54527-84-3 1 Calcium channel blockers.

11 AMLODIPINE BESILATE 111470-99-6 10 calcium channel blockers.

12 GLIBENCLAMIDE 10238-21-8 10 anti diabetic

13 DESLORATADINE 100643-71-8 1 antihistamine

14 VENLAFLAXINE

HYDROCHLORIDE 99300-78-4. 10 antidepressant

15 TELMISARTAN 144701-48-4 10 anti hypertension

16 PREGABALIN 148553-50-8 10 Anxiety disorders

17 FEBUXOSTAT 144060-53-7 10 hyperuricemia.

18 Vildagliptin 274901-16-5 10 anti diabetic

19 VALSARTAN 137862-53-4 10 Anti Hypertensive

20 TOPIRAMATE 97240-79-4. 1 antiepileptic

21 ROPIVACINE 132112-35-7 1 local anesthetic

22 PEDOTIMODE 121808-62-6 1 antineoplastic

23 R&D -- 1

TOTAL 149

14

LIST OF RAW MATERIALS

SR. NO. RAW MATERIAL QUANTITY

(MT/MONTH)

CAS NO.

NABIVILOL

1 NSR-19C 0.39

2 Methanol 60.47 67-56-1

3 Acetonitrile 1.19 75-05-8

4 Diisopropyl ether 2.38 108-20-3

5 HCl (CP) 0.24 7647-01-0

6 NSR-19D 0.14

7 IPA HCl (20%) 1.35 7647-01-0

8 Hyflow 0.68 61790-53-2

ZONISAMIDE

1 NSR-28A 25.00

2 NSR-28B 37.50

3 NSR-28C 44.17

4 Methanol 250.00 67-56-1

5 Ammonia Solution 62.50 1336-21-6

6 Hydrochloric Acid 75.00 7647-01-0

7 Ethyl Acetate 62.50 141-78-6

8 Ethylene Dichloride 122.50 107-06-2

9 NSR-28D 21.58

10 1,4 Dioxane 16.33 123-91-1

11 Phosphorus Oxy chloride 81.67 10025-87-3

12 Toluene 612.50 108-88-3

13 Ethyl Acetate 1020.83 141-78-6

14 Activated Carbon 20.83 7440-44-0

15 Hyflow Super cell 8.33 61790-53-2

16 Sodium Chloride 43.75 7440-23-5

17 Anhydrous ammonia 416.67 7664-41-7

18 Acetone 83.33 67-64-1

19 Activated carbon 16.67 7440-44-0

20 Hyflow supercel 4.17 61790-53-2

LORATADINE

1 Sulfuric acid 1.8 7664-93-9

2 Ice 60.0 7789-20-0

3 NaOH 8.29 1310-73-2

4 MDC 161.04 75-09-2

5 M-6 5.81

6 SOCL2 6.63 7719-09-7

7 DMF 0.27 68-12-2

8 HCl 33.11 7647-01-0

9 NaOH 40.67 1310-73-2

10 Hyflow 1.26 61790-53-2

15

11 Ethylene dibromide 0.47 106-93-4

12 THF 36.00 109-99-9

13 Mg. Turmings 1.02 7439-95-4

14 Iodine 0.01 7553-56-2

15 Ice 43.68 7789-20-0

16 HCl 9.85 7647-01-0

17 NaOH 1.36 1310-73-2

18 Chloroform 62.30 67-66-3

19 Hexane 4.50 110-54-3

20 Sulfuric acid 19.41 7664-93-9

21 Ice 19.70 7789-20-0

22 NaOH 15.66 1310-73-2

23 Toluene 58.72 108-88-3

24 Toluene 40.42 108-88-3

25 Ethylchlororo formate 2.35 541-41-3

26 NaHCO3 3.36 144-55-8


28 Carbon 0.13 7440-44-0

29 Hyflow 0.13 61790-53-2

30 Ethylacetate 2.50 141-78-6

31 carbon 0.13 7440-44-0

32 Hyflow 0.13 61790-53-2


34 Charcoal 0.05 7440-44-0

35 Hyflow 0.05 61790-53-2

FLUCANOZOLE

1 Triazole 25.00 288-88-0

2 trimethyl Iodidie 34.33 6966-83-2

3 Potassium Hydroxide 18.83 1310-58-3

4 Tertiary butyl Alcohol 20.00 76-65-0

5 Triazole 11.60 288-88-0

6 HCl 26.60 7647-01-0



9 Oxalic Acid 11.00 144-62-7

10 Charcoal 1.33 7440-44-0

11 Hyflow 1.67 61790-53-2

12 Ammonia Sol 13.33 1336-21-6

GLIMEPRIDE

1 Sulfonamide 1.92 63-74-1

2 Trans isocynate 0.62 7517-76-2

3 Acetone 28.85 67-64-1

4 Potassium carbonate 1.92 584-08-7

5 Glimepride crude 1.92 93479-97-1

6 Methanol 1.92 67-56-1

7 Ammonia Solution 1.92 1336-21-6

16

8 Hyflow super cell 0.04 61790-53-2


10 Acetone 57.69 67-64-1

11 DIODO 11.11 22662-39-1

12 Hydroxylamine hydrochloride 2.78 5470-11-1

13 Toluene 55.56 108-88-3




17 Hydrochloric acid 2.44 7647-01-0

18 Amiodarone Hydrochloride crude 11.11 1951-25-3

19 IPA 144.44 67-63-0



AMIODARONE HYDROCHLORIDE

1 DIODO 11.11 22662-39-1

2 Hydroxylamine hydrochloride 2.78 5470-11-1

3 Toluene 55.56 108-88-3





8 Amiodarone Hydrochloride crude 11.11 1951-25-3

9 IPA 144.44 67-63-0



CILOSTAZOL

1 1 cyclohexyal5 4 chlorobutyl

tetrazole 4.44

73963-42-5

2 Sodium hydroxide 3.56 1310-73-2

3 Tricapryal methyal ammonium

chloride 11.11

76925-99-0

4 Toluene 1.67 108-88-3

5 Methanol 33.33 67-56-1

6 6 hydroxy 2 oxo 1234 tetra

hydroxyl quanoline 6.67

54197-66-9

7 Ciostazole crude 11.11 73963-72-1

8 Methanol 166.67 67-56-1



APRIPITANT

1

2-{1-[3,5-

Bis(trifluoromethyl)phenyl]ethoxy}

-3-(4-fluorophenyl)morpholine

hydrochloride

12.0 171482-05-6

2 Amidrazone 5.0 3314-35-0

17

3 Potassium carbonate 13.O 584-08-7

4 Dimethyal formamide 30.0 68-12-2

5 O-xylene 96.5 95-47-6

6 Purified water 180 7732-18-5

7 Sodium chloride 4.5 7440-23-5

8 Methanol 25.0 67-56-1

9 Activated charcoal 0.2 7440-44-0

SEVELAMER HYDROCHLORIDE

1 Allylamine 10.00 107-11-9


3 Catalyst-A 0.10

4 Catalyst-B 0.10

5 Catalyst-C 0.10

6 Polyallylamine Hydrochlride 26.00 71550-12-4


8 Epichlorohydrine 1.00 106-89-8

NICARDIPINE HYDROCHLORIDE

1 2-Methylethanol amine 0.74 109-83-1

2 Benzyl chloride 1.44 100-44-7

3 TEA 1.59 121-44-8

4 Ethyl acetate 4.44 141-78-6

5 HCl 1.48 7647-01-0

6 Liquid Ammonia 2.22 1336-21-6

7 3-Nitrobenzaldehyde 0.33 99-61-6

8 Methyl 3-aminocrotonate 0.22 14025-39-1

9 Toluene 6.67 108-88-3

10 IPA 3.33 67-63-0

11 Acetone 22.22 67-64-1

12 Methanol 2.22 67-56-1


14 Sodium sulphate 0.37 7757-82-6

15 Liq. Ammonia 2.22 1336-21-6

16 HCl 1.67 7647-01-0

AMLODIPINE BESILATE

1 Ethyal 4-chloro aceto acetate 11.11 638-07-3

2 Hydroxyl Ethyal phalamide (HEP) 13.33 3891-07-4

3 Toluene 66.67 108-88-3

4 Acetic Acid 11.11 64-19-7

5 Methanol 0.22 67-56-1

6 Sodium hydride 5.56 7646-69-7

7 PHEEMA 11.11 88510-62-3

8 Ortho chloro benzaldehyde 5.56 89-98-5

9 Morpholine 0.44 110-91-8

10 Acetic acid 27.78 64-19-7

11 Methanol/IPA 38.89 67-56-1

12 Phthyloyl Amlodipne 11.11 88510-62-3

18

13 MMA 33.33 80-62-6

14 Amlodipne base on dry basis 11.11 88510-42-9

15 Benzene sulphonic Acid 6.78 98-11-3

16 Amlodipine base Crude 11.11 88510-42-9

17 IPA 55.56 67-63-0


GLIBENCLAMIDE

1 Butanone 21.85 78-93-3

2 5 chloro salicyclic acid 7.89 321-14-2

3 K2CO3 13.54 584-08-7

4 Dimethyl sulphate 13.14 77-78-1

5 EDC 31.38 25952-53-8

6 Dimethyl sulphate 13.14 77-78-1

7 Ester 0.00 533-23-3

8 Beta Phenyl ethylamine 4.91 3886-69-9

9 Sodium metal 0.08 7440-23-5

10 Methanol 1.44 67-56-1

11 EDC 54.09 25952-53-8

12 HCl 0.55 7647-01-0

13 Chloro sulphonic acid 32.20 7790-94-5

14 Amide sol 19.26 6485-52-5

15 Liq. Ammonia 114.50 1336-21-6

16 EDC 36.07 25952-53-8

17 Sulphonamide 12.96 63-74-1

18 NaOH 1.49 1310-73-2

19 CHIC 4.93 10238-21-8

20 Ammonia 1.23 1336-21-6

21 Hyflow 0.36 61790-53-2

22 Carbon 0.29 7440-44-0

23 Acetone 105.22 67-64-1

24 Methanol 234.53 67-56-1

25 HCl 6.49 7647-01-0

26 Hyflow 0.72 61790-53-2

27 Carbon 0.72 7440-44-0

DESLORATADINE

1 Loratadine 2.95 79794-75-5

2 Methanol 10.00 67-56-1

3 KOH 3.93 1310-58-3

4 MIBK 11.11 108-10-1

5 Charcoal 3.00 7440-44-0

6 Hyflow 3.50 61790-53-2

7 MIBK 0.83 108-10-1

VENLAFLAXINE HYDROCHLORIDE

1 Sodium methoxide 5.60 121-41-4

2 Methanol 5.00 67-56-1

3 PMPA 10.00 147127-20-6

19

4 Cyclohexane 9.30 110-82-7

5 IPA 25.00 67-63-0

6 Acetic acid 49.00 64-19-7

7 O-Xylene 16.60 95-47-6


9 Formic acid 19.00 64-18-6

10 Formaldehyde 16.70 50-00-0

11 NaOH 14.60 1310-73-2

12 Ethyl Acetate 90.00 141-78-6

13 Charcoal 0.40 7440-44-0


TELMISARTAN

1 Methanol 35.30 67-56-1

2 4- Amino 3-Methylbenzoic acid 14.84 2486-70-6

3 Sulphuric acid 14.23 7664-93-9

4 Liq. Ammonia 29.68 1336-21-6

5 MDC 56.70 75-09-2

6 TEA 13.14 121-44-8

7 Butryl chloride 12.87 141-75-3

8 Sodium Bicarbonate 1.53 144-55-8

9 Sodium Sulphate 3.87 7757-82-6

10 Hexane 50.94 110-54-3

11 Fuming Nitric acid 40.50 231-714-2


PREGABALIN

1 Sodium Hydroxide 18.99 1310-73-2

2 4-CMH 13.68

3 Liquid Bromine 12.25 7726-95-6


5 Hyflow 0.16 61790-53-2


7 Pregabalin (Stage-I) 11.76 148853-50-8

8 IPA 70.57 67-63-0

VILDAGLIPTIN

1 DMF 5.40 68-12-2

2 Methylene dichloride 15.00 75-09-2

3 Potassium Carbonate 2.60 584-08-7

4 Isopropyl Acetate 5.04 67-63-0

5 Sulphate 3.75 7757-82-6


7 Acetone 12.50 67-64-1

8 Charcoal 0.05 7440-44-0

FEBUXOSTAT

1 KSM 15.47 808-26-4

2 Isobutyl Bromide 11.62 78-77-3

3 Potassium Carbonate 18.34 584-08-7

20

4 Ammonium Hydroxide Hcl 3.23 1336-21-6

5 Sodium Carbonate 3.14 497-19-8



8 Acetone 7.50 67-64-1

VALSARTAN

1 L-Valine 25.64 72-18-4

2 Thionyl Chloride 41.28 7719-09-7

3 Methanol 152.05 67-56-1

4 Toluene 26.67 108-88-3

5 Acetone 81.03 67-64-1

6 Methyl Cyanobiphenyl 25.64 114772-53-1

7 Dibromodimethyl hydantion 18.97 77-48-5

8 AIBN 2.56 78-67-1

9 MDC 101.54 75-09-2

10 Ethyl Acetate 46.15 141-78-6


12 DMF 145.13 68-12-2

13 Toluene 199.74 108-88-3

14 HCl 14.87 7647-01-0


16 MDC 169.23 75-09-2

17 Valeryl Chloride 11.54 638-29-9

18 Triethylamine 9.74 121-44-8

19 HCl 15.38 7647-01-0


21 Xylene 88.21 1310-20-7

22 Tributyltinch Chloride 38.97 1461-22-9

23 Sodiumazide 7.69 26628-22-8

24 TBAB 0.51 1643-19-2


26 MDC 84.62 75-09-2


28 Ethyl Acetate 23.08 141-78-6

29 Xylene 44.10 1310-20-7

TOPIRAMATE

1 D-Fructose 1.43 57-48-7

2 Acetone 20.00 67-64-1

3 Sulfuric Acid 1.43 7664-93-9



6 IPA 0.71 67-63-0

7 Hexane 5.71 110-54-3

8 Topiramte satge1 1.43 97240-79-4

9 Sulfuryal chloride 0.71 7791-25-5

10 EDC 24.29 25292-53-8

21

11 Sodium bicarbonate 0.36 144-55-8


13 Anhydrous Ammonia gas 0.36 7664-41-7


15 Hexane 5.71 110-54-3

16 IPA 0.36 67-63-0



19 Topiramte crude 1.43 97240-79-4

20 IPA 4.29 67-63-0


22 Hexane 15.71 110-54-3



ROPIVACINE

1 L-Pipecolic acid 0.95 3105-95-1


3 L-Pipecolic acid Hydrochloric acid 0.95 3105-95-1

4 Phosphorous pentachloride 1.79 10026-13-8

5 Acetyl chloride 6.38 75-36-5

6 Acetone 34.67 67-64-1

7 Toluene 2.52 108-88-3

8 2,6 xylidine 1.40 87-62-7


10 Hexane 34.24 110-54-3



13 Sodium sulphate Anhydrous 1.36 7757-82-6

14 2,6 pipecoloxylidide 0.95 27262-43-7


16 Toluene 22.48 108-88-3

17 n - propyl bromide 2.19 106-94-5

18 IPA 4.00 67-63-0

19 Ethyl acetate 21.14 141-78-6

20 Activated charcoal 0.10 7440-44-0

21 Sodium bicarbonate 0.36 144-55-8


23 Sodium sulphate Anhydrous 2.07 7757-82-6

24 Hyflow supercell 0.10 61790-53-2

PEDOTIMODE

1 Thiazolidine-4-carboxylic acid ethyl

ester HCl 1.50

86028-91-3

2 L-Pyroglutamic acid 1.06 98-79-3


4 DCC (Dicyclohexylcarbodiimide) 1.72 538-75-0

5 Dichloromethane 20.00 75-09-2

22


7 HCl 0.50 7647-01-0

8 Acetone 3.75 67-64-1

9 Methanol 2.50 67-56-1

23

ANNEXURE-II

LAYOUT MAP OF THE PLANT

24

ANNEXURE-III

BRIEF PROCESS DESCRIPTION

1. NABIVILOL :

MANUFACTURING PROCESS

Stage-I :

(25) 6-Fluro –[(25) (oxiran-2yl)-3,4 dihydro-2H Chromene is reacted with benyl amine in IPA to

get Stage I product.

Stage-II :

Stage I product is hydrogenated in methanol in presence of palladium catalyst.

Stage-III :

StageI I product is reacted in Isopropyl alcohol hydrochloride to get NEBIVOLOL HCL

CHEMICAL REACTION

Stage-I : Prepartion of NB-IX (NE-3)

Stage-II : Prepartion of NB-IX (NE-3)

O

F

N O

F

OH OH

Benzyl Nebivolol HCl

NE 3

Pd/C, H2

MethanolIPA HCl

.HCl.HCl

O

F

NH O

F

OH OH

Nebivolol HClNL 1

25

MATERIAL BALANCE

Input material Quantity (KG) Output material Quantity (KG)

Stage-I

Stage-VIII (NE-2) 0.009 Dry Product 0.0148

NSR-19C 0.0058 MeOH Recovery 0.0405

Methanol 0.045 CFML 0.055

Acetonitrile 0.01756 Losses 0.01

Diisopropyl ether 0.03526

HCl (CP) 0.0036

Total 0.12 Total 0.12

Stage-II

Stage-IX (NE-3) 0.02 MeOH Recovery 0.765

Methanol 0.85 Dry wet 0.0059

NSR-19D 0.002 CFML 0.04

IPA HCl (20%) 0.02 Losses MeOH 0.085

Hyflow 0.01

Total 0.9 Total 0.9

28

2. ZONISAMIDE :


4 hydroxy Coumarin is reacted with Hydroxyl Amine Hydrochloride and Sodium acetate to get

stage-1 intermediate, which is further reacted with Chloro Sulphonic acid and Phosphorus Oxy

chloride to get crude material, which is further purified using Acetone and activated carbon to

ger Zonisamide.

CHEMICAL REACTION

Stage-I: Preparation of methyl 1,2-benzoxazol-3-ylacetate from NSR-28A

Stage-II: Preparation of Zonisamide Technical from crude

Stage-III: Preparation of Zonisamide from Zonisamide Technical

O O

OH

4-hydroxy-2H-chromen-2-one

Methanol

NH2OHO

N

COOH

1,2-benzoxazol-3-ylacetic acid

Sodium acetate

Methanol

O

N

COOCH3

methyl 1,2-benzoxazol-3-ylacetateM W = 162.14

M W = 177 .15 M W = 191.18

O

N

S

O

OCl

Chlorosulphonic acid

1,2-benzoxazol-3-ylmethanesulfonyl chloride

POCl 3

Ammonia

1-(1,2-benzoxazol-3-yl)methanesulfonamide

Zonisimide

M W = 231 .65M W = 212 .22

O

N

S

O

O

NH2

O

N

COOCH 3

methyl 1,2-benzisoxazol-3-ylacetateM W = 191 .18

29

MATERIAL BALANCE

Input material Quantity (KG) Output material Quantity (KG)

Stage-I

NSR-28A 0.06 MeOH recovery 0.54

NSR-28B 0.09 Aq layer 1.25

NSR-28C 0.106 Filtrate 0.65

Methanol 0.6 Dry Product 0.045

Ammonia Solution 0.15

Hydrochloric Acid 0.18

Ethyl Acetate 0.15

Purified Water 1.15


Stage-II

Stage-I 0.07 Product 0.04

Ethylene Dichloride 0.294 EDC Distillation 0.2646

NSR-28D 0.0518 Toluene Distillation 1.323

1,4 Dioxane 0.0392 EA Distillation 2.205

Phosphorus Oxy 0.196 Aq layer 2.2

Toluene 1.47 Rest ML rec losses 0.73

Ethyl Acetate 2.45

Activated Carbon 0.05

Hyflow Super cell 0.02

Sodium Chloride 0.105 7440-23-5

Anhydrous ammonia 1 cy

Purified Water 2.016


Stage-III

Stage-II 0.04 Dry Product 0.024

Acetone 0.2 Filtrate 0.7

Purified water 0.44 Loss in Drying & Filtration 0.01

Activated carbon 0.04

Hyflow supercel 0.01


30

3. Fluconazole :

Process Description: Manufacturing Process:

CT Base is reacted with Tri Methyl Sulphoxonium Iodide in presence of Potassium Hydroxide &

tertiary Butyl Alcohol to give FL1. FL1 is then purified & recrystallised using Ethyl Acetate to give

FL2. FL2 to is then coverted to Flucanazole Oxalate by reacting with oxalic acid in presence of

IPA. The material is also charcoalised & filtered in aqueous media at this stage for purification to

give FL3. FL3 is then dissolved & recrystallised in IPA Water Mixture to give pure Flucanazole.

Chemical Reaction:

31

Mass Balance:

33

4. LORATADINE : Manufacturing Process:

M-5 is reacted with Sulphuric acid and quenched to give M-6. M-6 is then chlorinated using

Thionyl chloride and AlCl3 catalyst to give M-7. M-7 is then reacted with Grignard reagent and

then acidified to give M-8. M-8 is then acidified and quenched to give Loratidine Crude.

The crude is then purified first using Acetonitrile. The product is further purified using Ethyl

acetate. Pure Loratidine is obtained by one more purification in Acetonitrile.

Chemical Reaction:

34

Mass Balance:

38

5. Glimepride and its Intermediate

Process Description: Stage-1:

A sulphanmide react with Tran’s isocynate in reflux in acetone with potassium carbonate after

reaction complies CF the mass and we get crystal filtration and drying finally we get Glimepride

Crude

Stage-2:

A Glimepride crude Slurry prepare in methanol this slurry is to be charge in Water finally and

charge ammonia solution and filter through pre prepared hyflow bed and clear filtrate to be

acidified with hydrochloric acid filter the mass centrifuge the mass wash the cake with water till

neutral PH and unload the cake drying and dry material purification do with acetone filter the

mass wet cake drying milling sifting or micronized and finally we get pure Glimepride

Route of Synthesis:

Stage-1

39

Stage:-1

Sr. No Input Material Kg Output Material Kg

1 Sulfonamide 1.00 Glimepride crude 2.00

2 Trans isocynate 0.32 Acetone CF ml 14.90

3 Acetone 15.00 Process Emission 0.22

4 Potassium carbonate 1.00 Drying loss 0.20


Stage:-2


1 Glimepride crude 1.00 Glimepride 0.52

2 Methanol 1.00 Acetone CF ML 29.5

3 Ammonia Solution 1.00 Acidic Water CF ML 23.5

4 Hyflow super cell 0.02 Drying loss 0.32

5 Hydrochloric Acid 1.00 Process emission 0.10

6 Acetone 30.0 Spent Hyflow 0.08

7 Water 20.0


40

6. Amiodarone Hydrochloride and its Intermediate


A Mixture of hydroxyl hydrochloride O2 solution in water addition reaction with DIODO with

at higher temperature in Toluene media with potassium carbonate after compilation of reaction

work up with water and finally organic toluene layer charcolisation and mass hydrolysis with HCl

and finally we get crystal filtration and drying finally we get Amiodarone crude.

Stage-2:

A Amiodarone crude dissolve in IPA at reflux temperature and dissolve mass pass through

hyflow carbon bed and cooling chilling and we get final crystallization , filtration and wash the

cake with IPA and drying milling sifting and micronisation finally we get final product

Amiodarone hydrochloride

Route of Synthesis:

41

Material Balance

Stage:-1


1 DIODO 1.00 Amiodarone Hydrochloride crude 1.23

2 Hydroxylamine hydrochloride 0.25 Water AQ layer 8.5

3 Toluene 5.0 Toluene CF ml 5.5

4 Potassium carbonate 1.0 Drying loss 0.2

5 Hyflow super cell 0.02 Spent Carbon and Hyflow 0.08

6 Activated carbon 0.02

7 Hydrochloric acid 0.22

8 Water 8.0


Stage:-2


1 Amiodarone Hydrochloride crude 1.00 Amiodarone Hydrochloride 0.9

2 IPA 13.0 IPA CF ML 12.7

3 Activated carbon 0.02 Drying loss 0.25

4 Hyflow super cell 0.02 Process emission 0.11

Spent Carbon and Hyflow 0.08


42

7. Cilostazol Crude


A Sodium hydroxide dissolve in water and then charge hydro 2 oxo tetrahydroquonoline and

then charge tetrazole then charge trimethyal ammonium chloride then charge toluene and finally

flush with water heat to reaction mass till reflux temperature centrifuge and caustic treatment

centrifuge and dry the finally we get cilostazol Crude

Stage-2:

A Cilostazol we dissolve in methanol charcolisation and filter through pre prepared hyflow bed

and clear filtrate to be crysalise the mass centrifuge the mass wash the cake with methanol and

unload the cake for drying and dry material drying milling sifting or micronized and finally we

get pure cilostazol

43

Route of

Synthesis:

NO

H

O

N

N

NN

Cl

Na2SO4

NaOH

N O

H

O

NN

N

N

+

5-(4-Chloro-butyl)-1-cyclohexyl-1H-tetrazole

Catalyst

6-Hydroxy-3,4-dihydro-1H-quinolin-2-one

Cilostazol

44

Material Balance

Stage:-1


1 1 cyclohexyal5 4 chlorobutyl tetrazole 0.4 Crude 2.00

2 Sodium hydroxide 0.32 Toluene CF ml 1.1

3 Tricapryal methyal ammonium chloride 1.00 Process Emission 0.22

4 Toluene 0.15 Drying loss 0.30

5 methanol 3.0 Methanol CF ml 2.7

6

6 hydroxy 2 oxo 1234 tetra hydroxyl

quanoline 0.6 Water Washing 19.5

7 Water 20.00

8


Stage:-2


1 Ciostazole crude 1.00 Cilostazole 0.9

2 Methanol 15.00 Methanol CF ML 14.9


4 Activated Carbon 0.02 Process emission 0.06

Spent Hyflow & Carbon 0.08


45

8. Sevelamer Hydrochloride and its Intermediate


A Mixture of Allylamine and Hydrochloric acid in low temperature with pressure of Nitrogen gas

to get Allylamine Hydrochloride. A Mixture of Allyamine Hydrochloride Catalyst A, B and C

and with controlled nitrogen gas to process of polymerization to get Plolyallyl amine

Hydrochloride.

Stage-2:

A Mixture of Sodium hydroxide, DM water and Polyallyamine Hydrochloride in the reaction

vessel at ambient temprature. Slowly add Epichlorohydrine to get gel formation at low

tempreture. Charge DM water and stir for 24 hrs to get final product.

Route of Synthesis:

Stage-1 :

NH2 CH2

Allylamine

+ NH2 CH2 .HClHCl

M. Weight: 57.09

C3H7NAllylamine Hydrochloride

C4H7ClN

M. Weight: 93.54

NH2 CH2 .HCl

Allylamine Hydrochloride

C4H7ClN

M. Weight: 93.54

Catalyst-A, B & C

Nitrogen gas

Polyallylamine Hydrochloride

Polymerization

46

Stage-2 :

Polyallylamine Hydrochloride

+ NaOH +

O

Cl

Water.HCl

Epichlorohydrine

C3H5ClO

M. Weight: 92.52

Sevelamer Hydrochloride

C6H12Cl2NO

M. Weight: 186.08

Material Balance

Stage:-1


1 Allylamine 1.00 Polyallylamine Hydrochlride 2.60

2 Hydrochloric acid 2.10 Water effluent 0.58

3 Catalyst-A 0.01

4 Catalyst-B 0.01

5 Catalyst-C 0.01

6 Nitrogen gas --

7 Water 0.05


Stage:-2


1 Polyallylamine Hydrochlride 2.60 Sevelemer Hydrochloride 1.00

2 Sodium hydroxide 0.41 Water effluent 8.09

3 Epichlorohydrine 0.10 Drying loss 0.25

4 Nitrogen gas -- Process emission 0.10

5 Water 6.33


47

9. Nicardipine Hydrochloride and its Intermediate

Process Description:

Stage-1:

Charge 2-methylethanol amine in presence of TEA with Benzyl chloride in SSR reactor. Heat to

reflex temperature to completion of reaction. Then slowly add hydrochloric acid and reaction

mass extracted in Ethyl acetate. Cooling, chilling and distilled ethyl acetate and get product in

liquid form.

Stage-2:

Charge 1-{2-[benzyl(methyl)amino]ethoxy}ethanol in presence of Isopropyl alcohol and Toluene

with 3-Nitrobenzaldehyde and Methyl 3-aminocrotonate in SSR reactor. Heat to reflex

temperature to completion of reaction. Then slowly add hydrochloric acid and reaction mass

extracted in Ethyl acetate. Cooling, chilling and CF to give Technical grade Nicardipine

Hydrochloride and purified with methanol, heat to clear solution, filtration and distillation of

methanol then charge acetone to give Nicardipine Hydrochloride.

Route of Synthesis:

Stage-1 :

HO

HN

2-methylaminoethanol

TEA/Benzyl chloride

OH

O

N

1-{2-[benzyl(methyl)amino]ethoxy}ethanol

48

Stage-2:

M. Weight: 209.28M. Weight: 115.13

NO CH3

CH3 OH

+N

+

O-

O

O

+

3-Nitrobenzaldehyde

NH2

CH3

O

O

CH3

Methyl 3-aminocrotonateC

12H

19NO

2C

7H

5NO

3

M. Weight: 151.12

C5H9NO2

NH

O

OCH3

N+

O-

O

ON

O CH3

CH3CH3

C26

H30

ClN3O

6

.HCl

Nicardipine Hydrochloride

M. Weight: 515.99

1-{2-[benzyl(methyl)amino]ethoxy}ethanol

Material Balance

Stage:-1


1 2-Methylethanol amine 1.00 Stage-I 1.50

2 Benzyl chloride 1.95 Ethyl acetate recovery 5.00

3 TEA 2.15 Water effluent 10.9

4 Ethyl acetate 6.00 Process emission 0.20

5 HCL 2.00

6 Liquid Ammonia 3.00

7 Water 1.50


Stage:-2


1 Stage-I 1.50 Nicardipine Hydrochloride 1.35

49

2 3-Nitrobenzaldehyde 0.45 Toluene recovery 8.25

3 Methyl 3-aminocrotonate 0.30 Acetone recovery 27.6

4 Toluene 9.00 IPA recovery 4.23

5 IPA 4.50 Sodium sulphate solid waste 0.50

6 Acetone 30.0 Sodium chloride solid waste 0.50

7 Methanol 3.00 Water effluent 15.82

8 Sodium chloride 0.50 Drying loss 0.25

9 Sodium sulphate 0.50 Process emission 0.50

10 Liq. Ammonia 3.00

11 HCl 2.25

12 Water 4.00


50

10. Amlodipine besilate and its Intermediate

Process Description: Stage-1 : ( PHEEMA)

A reaction of 4-methyal 4 chloro acetoacetae react with sodium hydride in presence of toluene

reaction with lot wise HEP till reaction complies with acetic acid and clean with methanol and

work up after work toluene layer distilled out completely and finally degas we get final liquid

product is PHEEMA

Stage-2:

PHEEMA reaction with OCB in Acetic acid in presence of morphline and Addition reaction after

reaction complies distilled out Acetic acid and add additional acetic acid and second reaction with

MAC and within the higher side temperature side after maintaining reaction complies batch

centrifugation and crude wet cake purification in methanol and finally cake wash with methanol

centrifugation and Drying and unload finally product is Pthyloyal amlodipine

Stage-3:

Pthyloyal amlodipine react with MMA staring and maintain centrifugation and finally cake wash

with water till neutral PH and wet cake as a crude wet cake Amlodipine besilate base

Stage-4:

Amlodipine besilate base wet cake hydrolysis in BSA solution starring and maintaining filtration

and finally cake wash with water till neutral PH and drying and packing finally we get final

product is Amlodipine besilate crude

Stage-5:

Amlodipine Besilate dissolves in IPA and filter throughhyflow bed in sparkler clear filtrate

crystallization centrifuge and drying sifting and packing and fillay we get final product is

Amlodipine besilate

52

Route of Synthesis:

Mono Methyl Amine

4-(2-Chlorophenyl)-3-ethoxycarbonyl-5-methoxy

carbonyl-6-methyl-2-(phthalimidoethoxy)

methyl-1,4-dihydropyridine (Phthaloyl Amlodipine)

MW 538.98

N

H

CH3

H3COOC COOC2H5

Cl

ON

O

O

MW 31.05

3-ethyl 5-methyl 2-[(2-aminoethoxy)

methyl]-4-(2-chlorophenyl)-6-methyl-1,4-dihydro

pyridine-3,5-dicarboxylate

MW 408.87

N

H

CH3

H3COOC COOC2H5

Cl

ONH2

HCH3 N

O

O

+

2 Methyl-1-isoindole-1,3-dione

MW 161.16

53



pyridine-3,5-dicarboxylate amlodipine Besylate

N

H

CH3

H3COOC COOC2H5

Cl

ONH2

H



pyridine-3,5-dicarboxylate

MW 408.87

N

H

CH3

H3COOC COOC2H5

Cl

ONH2

H+

Benzene Sulfonic Acid

MW 158.17

SO3H

SO3H

.

MW 567.05

Material Balance

Stage:-1


1 Ethyal 4-chloro aceto acetate 1.00 PHEEMA 1.90

2 Hydroxyl Ethyal phalamide (HEP) 1.2 Water AQ layer 4.4

3 Toluene 6.0 Distilled Toluene 6.22

4 Acetic Acid 1.0 Process Emission 0.2

54

5 Methanol 0.02

6 Sodium hydride 0.5

7 Water 3.0


Stage:-2


1 PHEEMA 1.00 Phthyloyl Amlodipne 0.93

2 Ortho chloro benzaldehyde 0.5 IPA/Methanol CF ML 3.7

3 Morpholine 0.04 Acetic Acid CF ML 2.7

4 Acetic acid 2.5 Drying loss 0.1

5 Methanol/IPA 3.5 Process emission 0.11


Stage:-3


1 Phthyloyl Amlodipne 1.00 Amlodipne base on dry basis 0.68

2 MMA 3.0 MMA CF ML 3.42

3 water 6.0 Washing Water 5.8

Process emission 0.1


Stage:-4


1 Amlodipne base on dry basis 1.00 Amlodipine base Crude 1.4

2 Benzene sulphonic Acid 0.61 Water CF ML 8.0

3 water 8.0 Drying loss 0.21


Stage:-5


1 Amlodipine base Crude 1.00 Amlodipine besilate 0.9

2 IPA 5.0 IPA CF ML 4.9


Process Emission 0.11

Spent hyflowsuper cell 0.1


55

11. Glibenclamide for EC:

Manufacturing Process:

5-chloro Salicylic acid is reacted with DMS in presence of Butanone and K2CO3 to give Ester. The

ester is then converted to Amide by reacting with β-Phenyl Ethyl amine. Amide is treated with

Chloro sulphonic acid and Ammonia to give Sulphonamide. The Sulphonamide is then treated

with CHIC to form CHIC salt. The CHIC salt is then converted to Glibenclamide by addition of HCl.

Chemical Reaction:

OH

O OH

Cl

+ (CH3) 2SO4

K2CO3/ EDC O

O O

Cl

CH3

CH3

5-chloro-2-hydroxybenzoic acid methyl 5-chloro-2-methoxybenzoate

NH2

O

O

Cl

CH3

NH

5-chloro-2-methoxy-N-(2-phenylethyl)benzamide

Sodium Metal, EDC

M. Wt : 289. 5

O

O

Cl

CH3

NH

5-chloro-2-methoxy-N-(2-phenylethyl)benzamide

M. Wt : 289. 5

Chlorosulphonic acid

Liq. ammonia

O

O

Cl

CH3

NH

SO

ONH2

M. Wt : 368. 5

+

O

O

Cl

CH3

NH

S

O

ONH

NH

O

( 1) NaOHLiq. Ammonia/Acetone

M. Wt : 493. 5

N

O

isocyanatocyclohexane

( 2) Methanol/HCl

56

Mass Balance:

STEP 1 ; ESTER PREPARATION

INPUT :

OUTPUT :

Raw Material Input , Kgs

Product Output, Kgs

CO2 Gas 0.189

Butanone 2.185

Distillate : 5- Chloro Salicyclic acid 0.789 Butanone 1.971

K2CO3 1.354 Mass : Dimethyl Sulphate 1.314 Mass 3.268

Total 5.642 Losses 0.214

Total 5.642

INPUT :

Raw Material Input , Kgs OUTPUT :

Mass 3.268

Product Output, Kgs

Water 4.303

Aqueous layer to ETP * 5.944

EDC 3.138

Organic layer 5.766

Dimethyl Sulphate 1.314 Losses 0.314


INPUT :

OUTPUT :


Product Output, Kgs

Organic layer 5.766 Organic layer

Aqueous layer to ETP * 0.917

Water 0.717 Organic layer 4.990

Losses 0.577


INPUT : OUTPUT :

Raw Material Input , Kgs Product Output, Kgs

Organic layer 4.990 EDC 2.914

Total 4.990 Ester 0.861

Losses 0.998

Residue to Incinerator * 0.215

Total 4.988

STEP 2 : AMIDE PREPARATION

INPUT :

INPUT :



Ester 0.729 Distillate : Beta Phenyl Ethylamine 0.491 Methanol 0.182

Sodium metal 0.008 Layers:

Methanol 0.144 Aqueous layer to ETP * 1.220

EDC 5.409 Organic layer 5.757

HCl 0.055 Losses 0.541

Water 0.865 Total 7.701

Total 7.701

INPUT : OUTPUT :


Product Output, Kgs

Organic layer 5.757 Aqueous layer to ETP * 1.642

Water 1.442 Organic layer 4.981

Total 7.200 Losses 0.576

Total 7.200

INPUT : OUTPUT :


Organic layer 4.981 EDC 2.308

Total 4.981 Organic layer with EDC 1.926

Losses 0.747

Total 4.981

STEP 3 : SULPHONAMIDE PREPARATION :

INPUT :

OUTPUT :


Product Output, Kgs

Chloro Sulphonic acid 3.22493684 Hcl to scrubber 1

Amide solution 1.926

Sulphonamide Wet Cake 2.078

Liquor Ammonia 11.458 ML to ETP * 24.119

EDC 3.607

Losses 1.338

Water 11.543 Total 28.535

Total 28.535

INPUT : OUTPUT :


Sulphonamide Wet Cake 2.078 Sulphonamide Dry Cake 1.293

Total 2.078 Losses on drying 0.785

Total 2.078

Esterification & Distillation

Extraction

Water wash

Distillation

Amide Preparation ,

Distillation & Extraction

Water Wash

Distillation

Sulphonamide preparation &

Centrifuge

Drying

57

STEP 4 : CHIC SALT PREPARATION :

INPUT :


OUTPUT :

Sulphonamide 1.296 Product Output, Kgs

NaOH 0.149 Nutchefilteration

CHIC 0.493 Solids to Incinerator * 0.097

Ammonia 0.123 Cake Centrifuge :

Hyflo 0.036 CHIC wet salt 1.800 Carbon 0.029 ML for recovery - I 8.646 Acetone 10.522 Losses 2.104 Total 12.648 Total 12.648

STEP 5 : GLIBENCLAMIDE :

INPUT : OUTPUT :


Product Output, Kgs

Methanol 23.453 Nutchefilteration

CHIC salt 1.763 Solids for incinerator 0.216 HCl 0.649 Cake Centrifuge :

Water 15.873 CHIC wet salt 1.429 Hyflo 0.072 ML for recovery - II 17.775

Carbon 0.072 ML for ETP 17.772

Total 41.882 Losses 4.691 Total 41.882

INPUT : OUTPUT :


Product Output, Kgs

Glibenclamide wet cake 1.429 Glibenclamide Dry Cake 1.000 Total 1.429 Losses on drying 0.429

Total 1.429

For Packing in Drums

ML FOR RECOVERY - I

INPUT : OUTPUT :


ML for recovery - I 8.646 Acetone distilled 6.825 Water 3.571 II crop 0.179 Total 12.217 Losses 1.297

ML to ETP * 3.917 Total 12.217

ML FOR RECOVERY - II

OUTPUT :

INPUT : Product Output, Kgs

Raw Material Input , Kgs Methanol 14.813

ML for recovery - II 17.775 Residue to Incinerator * 0.296 Total 17.775 Losses 2.666

Total 17.775

CHIC Salt Preparation ,

Filteration & Centrifuge

Glibenclamide Preparation,

Filteration & Centrifuge

Drying

Sifter

Microniser

Distillation

Distillation

58

12. Desloratadine for EC :


Loratidine is refluxed with Methanol. The Material is then extracted in MIBK after Methanol

removal. The product is then crystallized after distillation of MIBK to give Desloratidine.

Chemical Reaction:

59

Mass Balance:

60

13. Venlaflaxine Hydrochloride for EC :


Cyclohexanone is condensed with Para Methoxy Phenyl acetonitrile to give VF1. This VF1 is

reduced using palladium charcoal as catalyst. Acetic acid is used to get VF2 during this step. This

VF2 is reacted with Formic Acid & formaldehyde to Venlaflaxine base. Venlaflaxine

Hydrochloride is obtained by condensation of this base with IPA HCl.

Chemical Reaction:

Material Balance:

62

Step 3 Venlaflaxine Preparation

INPUT : OUTPUT :


VF2 Acetate 1.25 Mass 17.32

Formic Acid 1.90

Formaldehyde 1.67

Water 12.50


INPUT : OUTPUT :


Mass 17.32 Aq. To ETP * 23.22

NaOH 1.46 Mass 9.35

Water 4.79

Ethyl Acetate 9.00


INPUT : OUTPUT :


Mass 9.35 Cake to Inc. * 0.04

Charcoal 0.04 Mass 10.10

Ethyl Acetate 0.75



Mass 10.10 Distilled EA 8.70

EA 1.50 Losses 1.80

Mass 1.10


INPUT : OUTPUT :


Mass 1.10 Mass 2.10

IPA HCL 1.00


INPUT : OUTPUT :


Mass 2.10 EA Rec. 1.50

EA 0.75 Mass 1.10

Residue to Inc. * 0.25


INPUT : OUTPUT :


Mass 1.10 Losses 0.10

Venlafaxiine 1.00


Reaction

&pH Adjustment

Filtration

pH Adjustment

&Extraction

EA Recovery

Reaction

Centrifuge & Solvent

Recovery

Drying

63

14. Telmisartan for EC :


4-Amino-3-benzoic acid is esterifies to gives methyl-4-amino-3-bezoate, which reacted with

butryl chloride to produce butyramide derivative, which nitrated with fuming nitric acid to

produced nitro derivative, which reduced in presence of Palladium on charcoal and then

hydrolyzed to gives benzimidazole derivative. Benzimidazole is reacted with n-methyl o-

phenylene diamine to gives condensed product, which is reacted with bromo ester to gives telmi

ester, which hydrolyzed with potassium hydroxide to gives Telmisartan.

Chemical Reaction:

CH3

NH2

O

OH

CH3

CH3

O

O

NH2

O

TS-1

M wt - 165

CH3OH/H2SO4

65°C

Yield 94 %

CH3

CH3

O

O

NH2

CH3Cl

O CH3

CH3

O

O

NH CH3

O

CH3

CH3

O

O

NH CH3

OCH3

CH3

O

O

NH CH3

O

NO2

CH3

CH3

O

O

NH CH3

O

NO2

Pd/CharcoalAcetic Acid

CH3

CH3

CH3

O

O

NH

N

CH3

CH3

CH3

O

O

NH

N

CH3

CH3

H

O

O

NH

N

10% NaOH Sol.

Methanol

CH3

CH3

H

O

O

NH

N

CH3

CH3

NH

N

N

N

CH3Polyphospheric Acid

NH2

NHCH3

TS-1

TS-2

M wt - 235

TS-3

M wt - 280

TS-5

M wt - 232

TS-6

M wt - 218

TS-7M wt - 304

Fuming HNO3

-20 to -25°C

0 to 5°C

80°C

140 to 145°C

Yield 96 %

Yield 93 %

Yield 86 %

Yield 96 %

TEA/MDC

64

Mass Balance:

Qty (Kg) Raw material Material Qty(Kg)

3.53 Methanol ML to ETP 7.574

1.484 4-Amino 3-Methylbenzoic acid

1.423 Conc. Sulphuric acid

2.968 Liq. NH3

9.410 Total Output 1.53Loss 0.31


1.53 TS-1 Soduim Sulpahte 0.387

5.670 MDC Aqs. Layer 12.240

1.314 TEA Recovered MDC+Hexane 6.0841.287 Butryl chloride ML to ETP 7.7050.153 Sodium Bicarbonate

0.387 Sodium Sulphate

12.240 Water

5.094 Hexane



0.90 TS-2 ML to ETP 12.748

4.050 Fuming Nitric acid

0.090 Sodium Bicarbonate

9.000 DM Water


INPUT OUTPUT

TS-01

INPUT OUTPUT

TS-02

INPUT OUTPUT

TS-03

65

15. Pregabalin for EC :

Manufacturing Process

Sodium Hydroxide solution in Process water is chilled at 0-10°C and then charge R-(-)-3-

(Carbamoylmethyl)-5-methylhexanoic acid [R-(-)-CMH]. Addition of liquid Bromine is done at 0-

5°C then raise the temperature of the reaction mass up to 30-35°C. After reaction monitoring,

raise the temperature of the reaction mass to 55-60°C and apply carbon treatment. The clear

filtrate is then received in another reactor. Excess water is distilled off from the reaction mass.

The reaction mixture is acidified with concentrated Hydrochloric acid. Reaction mass is then up

to 80-85°C and after that gradual cooling to 25-30°C. The material is centrifuged after

maintaining of the reaction mass at 25-30°C for 4-6 hrs.

The dry material is then charged in IPA and raises the temperature to 80-85°C. Add DM water to

reaction mass at 80-85°C. Filter the clear reaction mass and chill it to 8-12°C. The material is then

centrifuged and dried in under vacuum.

Chemical Reaction

66

Material Balance

Stage - 1

Sr.

No.

Raw Material Quantity Kgs Out Put Quantity

Kgs

1

Process water 2590.0

Spent carbon and

hyflo 28.0

2 Sodium Hydroxide 347.2 Spent ML 3623.7

3 4-CMH 250.0 Loss on drying 62.5

4 Liquid Bromine 224.0 Out Put 162.5


6 Hyflo 3.0

7 Hydrochloric acid 450.0

Total 3877 Total 3877

Stage - 2

Sr.

No.

Raw Material Quantity Kgs Out Put Quantity

Kgs

1 Pregabalin (Stage-I) 215.0 Spent ML 2150.00

2 IPA 1290.0 Loss o Drying 32.2

3 DM water 860.0 Out Put 182.8


67

16. Vildagliptin for EC :


Stage 1

Reaction of (2s)-1-(Chloroacetyl)-2-Cyanopyrrolidine (KSM-II) with 3-Amino-1-Hydro-

Xyadamantine (KSM-I) in presence of Potassium Carbonate and Dimethyl Formamide (DMF) as a

solvent gives Vildagliptin crude.

Stage 2

Vildagliptin crude is purified by treatment of Aq. Potassium Hydrogen Sulphate and Aq.

Potassium Carbonate in presence of Dichloromethane, followed by Acetone crystallization to

give Vildagliptin API.

MDC,Acetone and DMF are recovered and reused.Aqueous effluent is taken to ETP for

treatment.

CHEMICAL REACTION:

68

MATERIAL BALANCE:

Sr.

N0. Input material Quantity/ (KG) Output material

Quantity

/(KG)

1 KSM I 0.77

Vildagliptin 1

2 KSM II

0.72

Recovered Methylene

Dichloride 13.44

3 DMF 5.4 Recovered Acetone 10.12

4 Methylene dichloride 15

Recovered DMF 5.68

5 Potassium Carbonate

2.6

Vapor losses through

Vent 1

6 Isopropyl Acetate

5.04

Potassium

Carbonate(cake) 1.2

7 Sulphate 3.75

Hyflow + charcoal 1.6

8 Sodium chloride 0.63

Effluent to ETP 17.42

9 Acetone 12.5

10 Charcoal 0.05

11 Water 5


69

17. Febuxostat for EC :


Ethyl-2-(3-formyl-4-isobutoxyphenyl)-4-methylthiazole-5-carboxylate is reacted with

hydroxylamine hydrochloride to form oxide which is dehydrated with sodium formate & formic

acid to form Ethyl 2-(3-cyano-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylate which on

hydrolysis gives Febuxostate. Process involves formation of Ethyl 2-(3-Formyl-4-

Isobutoxyphenyl)-4-Methylthiazole-5-carboxylate,Ethyl 2-(3-Cyano-4-Isobutoxyphenyl)-4-

Methyl-5-thiazole carboxylate and finally febuxostate. The reactions are carried out in three

different reactors .Acetone is recovered and reused while aqueous effluent is taken to ETP.

70

CHEMICAL REACTION

71

MATERIAL BALANCE

Sr.No. Input material Quantity

(KG) Output material

Quantity

(KG)

1 KSM 1547 Febuxostat 1000

2 Isobutyl Bromide 1162 Evaporation losses 565

3 Potassium

Carbonate 1834 Recovered Acetone 700

4 Ammonium

Hydroxide Hcl 323 Effluent to ETP 5451

5 Sodium

Carbonate 314

6 Sodium

Hydroxide 297

72

7 Hydrochloric

Acid 289

8 Acetone 750

9 Water 1200


73

18. Valsartan for EC :


L – Valine reacts with thionyl chloride in the presence of methanol at 5degC which is further

refluxed for 12hrs and then concentrated , precipitated with acetone to give VST-01. Methyl

cyano bi phenyl reacts with dibromodimethylhydantion in the presence of AIBN and DCM at

reflux temp. for 13hrs which is further worked up, filtered , dried to give VST -02 . VST – 01 then

reacts with VST – 02 in the presence of potassium carbonate and dimethyl formamide at RT to

give VST -03,this is again treated with sodium bicarbonate in the presence of dichloromethane

and water where a base compound is obtained. This compound further reacts with valeryl

chloride and triethylamine at 5degC where it is worked up and charcolised to give VST -04

dissolved in xylene. This liquid mass further reacts with sodium azide , tributyltinchloride and

TBAB at 140degC for 42hrs ,it is further worked up and charcolised to give Valsartan.

74

Mass Balance:

INPUT OUTPUT

Qty

(Kg) Raw material Material Qty(Kg)

VST-1.HCl

1.000 L-Valine Recovered methanol 5.041 85 % of

Input

Methanol

1.610 Thionyl Chloride Recovered Toluene (Toluene

+ Thionyl Chloride)

1.525

5.930 Methanol Filtrate (Acetone + Toluene

Traces)

3.054

1.040 Toluene

3.160 Acetone

12.740 Total Output 1.000

Loss 2.120

INPUT OUTPUT

Qty


VST-2

1.000 Methyl Cyanobiphenyl Aqs. Layer (Water + MDC

Traces + AIBN)

4.179

0.740 Dibromodimethyl

hydantion

Recovered MDC 3.564 90% of

input DCM

0.100 AIBN Recovered E.Ac. (E.Ac.+ MDC

Traces)

0.090

3.960 MDC Filtrate (E.Ac.) 1.620

1.800 Ethyl Acetate

4.000 DM Water


Loss 1.047

75

INPUT OUTPUT

Qty


VST-3

1.000 VST-02 Org. Layer (Toluene + Water

Traces)

7.551

0.800 VST-01.HCl Filtrate (Water + DMF + HCl +

Potassium Chloride )

21.024

0.500 Potassium carbonate

5.660 DMF

7.790 Toluene

0.580 HCl

15.000 DM Water


Loss 1.756

INPUT OUTPUT

Qty


VST-4

1.000 VST-03.HCl Aqs.Layer (NaHCO3 + HCl +

MDC Traces + Water)

3.258

0.950 Sodium Bicarbonate Aqs.Layer (TEA + NaHCO3 +

HCl + MDC Traces + Water +

Excess Varelyl Chloride)

14.761

6.600 MDC Recovered DCM 5.610 85% of

input DCM

0.450 Valeryl Chloride Activated Carbon (Carbon +

Xylene)

0.150

0.380 Triethylamine

0.600 HCl

0.100 Activated Carbon

3.440 Xylene

15.400 DM Water


Loss 0.751

76

INPUT OUTPUT

Qty


VALSARTAN

1.000 VST-04 Org. Layer (Xylene + Excess

Tributyltinch Chloride)

2.348

1.520 Tributyltinch Chloride Aqs. Layer (Water + Xylene

Traces +Excess Sodiumazide

+ TBAB + Sodium Hydroxide)

1.595

0.300 Sodiumazide Aqs. Layer (Water + MDC

Traces)

2.066

0.020 TBAB

Recovered DCM

2.805 85% of

input DCM

0.400 Sodium Hydroxide Activated Carbon (Carbon +

E. Ac.)

0.150

3.300 MDC Filtrate (Ethyl Acetate +

MDC)

1.515

0.100 Activated Carbon

0.900 Ethyl Acetate

1.720 Xylene

3.000 DM Water


Loss 1.390

77

19. Topiramate and its Intermediate


A D-fructose hydrolyzed with sulfuric acid in acetone after reaction complies adjust the PH with

sodium hydroxide solution filter the salt filtration sodium sulfate salt to be remove as a spent and

clear filtration take for distillation after degassing add water and work up with IPA and hexane

and finally centrifuge the mass wash the cake with water cake drying finally get the final product

as Topiramte Stage 1

Stage-2:

Topramte stage 1 reaction done with sulfuryal chloride in EDC after reaction complies Reaction

mass work up with water and give sodium bi carbonate wash and finally EDC layer wash with

sodium chloride was after work up distilled out EDC completely and adjust the mass PH with

anhydrous ammonia filter the mass through charcoal and hyflow bed clear filter is to be distilled

out completely change Ethyl acetate and IPA and finally crystallization in hexane cooling and

chilling and filter the mass through centrifuge finally we get product as a Topiramate crude

Stage-3:

Topiramate crude dissolve in IPA and Ethyl acetate chrcolise the mass filter the clear filtrate heat

clear and hexane addition after crystallization filter the mass and finally wash the cake with water

drying milling sifting and packing and we get finally product as Topramate

78

Material Balance

Stage:-1


1 D-Fructose 1.00 Topiramte satge1 0.8

2 Acetone 14.0 Distilled Acetone 11.5

3 Sulfuric Acid 1.0 Hexane + water CF ML 9.5

4 Sodium hydroxide 1.5 Drying loss 0.25

5 Water 3.0 Sodium sulfate spent salt 3.34

6 Ethyl Acetate 0.5 Process emission 0.11

7 IPA 0.5

8 Hexane 4.0


79

Stage:-2


1 Topiramte satge1 1.0 Topiramte crude 0.8

2 Sulfuryal chloride 0.5 Distilled EDC 11.5

3 EDC 17.0 Hexane + ethyl+ IPA CFML 9.62

4 Sodium bicarbonate 0.25 Water aqueous layer 11.6

5 Water 10.5 Activated carbon and hyflow spent 0.5

6 Sodium chloride 0.25 Process emission 0.11

7 Anhydrous Ammonia gas 0.25

8 Ethyl acetate 0.25

9 Hexane 4.0

10 IPA 0.25


12 Hyflow super cell 0.02


Stage:-3


1 Topiramte crude 1.00 Topiramte 0.7

2 IPA 3.00 Hexane + ethyl+ IPA CFML 15.7

3 Ethyl acetate 2.00 Drying loss 0.2

4 Hexane 11.00 Water CF ML 3.23

5 Activated carbon 0.02 Process emission 0.11

6 Hyflow super cell 0.02 Spent Carbon and Hyflow 0.1

7 water 3.00


80

20. Ropivacine and its Intermediate


Stage-1: L-Pipecolic acid hydrochloride

L-Pipecolic acid react with toluene in hydrolyzed with hydrochloride acid purified gives L-

Pipecolic acid hydrochloric acid

Stage-2:2,6 L- Pipiecoloxylidide

. L-Pipecolic acid hydrochloride reacts with phosphorous penta chlorides in presences of acetyls

chloride in toluene wash with acetone and re action with 2, 6 xylidine in reaction with ethyl

acetate in hexane with sodium chloride finally treat with sodium sulphate anhydrous gives 2,6 L-

Pipiecoloxylidide

Stage-3: Ropivacaine

2, 6 L- Pipiecoloxylidide react with n propyl bromide in presences of potassium carbonate in

toluene wash with IPA and ethyl acetate finally charcolised filtrated treated with sodium sulphate

finally gives Ropivacaine.

81

Route of Synthesis:

NH

COOH

NH

COOH

.HCl

HCl

NH

COCl

O2N

NH

HN

O

NH

COOH

NH

COCl

N

HN

O

.HCl

NH

HN

O

.HCl

Stage-I

Stage-III

ACCl/PCl5

Acetone

+ Acetone

2,6- L-Pipocoloxylidide

L-Pipecolic acid

2,6- L-Pipocoloxylidide

Stage-II

n-Propyl bromide

IPA/K2CO3

Ropivacaine

82

Material Balance

Stage:-1


1 L-Pipecolic acid 1.00 L-Pipecolic acid Hydrochloric acid 0.98

2 Hydrochloric acid 0.2 Water effluent 0.22

Total 1.2 Total 1.2

Stage:-2


1 L-Pipecolic acid Hydrochloric

acid 1.0 2,6 pipecoloxylidide 2.0

2 Phosphorous pentachloride 1.88 Toluene CF ML 6.7

3 Acetyl chloride 6.7 Acetone CF ML 35.1

4 Acetone 36.4 Ethyl acetate impurity layer 23.5

5 Toluene 2.65 AQ Layer 13.5

6 2,6 xylidine 1.47 Spent sodium sulpahte 4.0

7 Ethyl acetate 22.70 Sodium chloride AQ Layer 6.2

8 Hexane 35.95 Hexane CF ML 30.2

9 Sodium hydroxide 0.5 Drying loss 1.0

10 Purified water 11.0 Emission loss 0.48

11 Sodium chloride 1.0

12 Sodium sulphate Anhydrous 1.43


Stage:-3


1 2,6 pipecoloxylidide 1.0 Ropivacaine 1.05

2 Potassium carbonate 0.41 Water effluent 23.5

3 Toluene 23.60 Aq layer 8.5

4 n - propyl bromide 2.3 Toluene CF ML 21.7

5 IPA 4.2 Ethyl acetate CF Ml 19.5

6 Ethyl acetate 22.2 Spent charcoal and highf-low 2.1

7 Activated charcoal 0.1 Spent sodium sulfate 3.6

8 Sodium bicarbonate 0.38 Drying loss 0.25

9 Sodium chloride 0.54 Process emission 0.10

10 Sodium sulphate Anhydrous 2.17 IPA impurity layer 5.7

11 Hyflow supercell 0.1

12 Purified water 29

Total 86 Total 86.0

83

21. Pidotimod and its Intermediate


Thiazolidine-4-carboxylic acid ethyl ester HCl reacts with DCC in presences of L-Pyroglutamic

acid in dichloromethane after reaction product hydrolyzed with sodium hydroxide gives

Pidatimod.

Route of Synthesis:

S

NH

O O

.HCl

S

N

O OH

O

HN

O

Thiazolidine-4-carboxylic acid ethyl ester HCl

DCC/L-Pyroglutamic acid

Pidotimod

M.W : 197.5 M.W : 244.26

Material Balance


1

Thiazolidine-4-carboxylic acid

ethyl ester HCl 1.50 Pidotimod 1.00

2 L-Pyroglutamic acid 1.06 Dichloromethane recovery 18.8

3 Potassium carbonate 1.50 Acetone CF ML 3.50

4 DCC (Dicyclohexylcarbodiimide) 1.72 Methanol CF ML 2.20

5 Dichloromethane 20.0 Solid waste 2.10

6 Sodium hydroxide 0.33 Aq. Effluent 21.76

7 HCl 0.50 Drying loss 0.20

8 Acetone 3.75 Process emission 0.30

8 Methanol 2.50

10 Purified water 17.00


84

22. Aprepitatant and its Intermediate


A reaction with 2-{1-[3,5-Bis(trifluoromethyl)phenyl]ethoxy}-3-(4-fluorophenyl)morpholine

hydrochloride and Amidrazone with potassium carbonate in presence of DMF anf o xylene work

with sodium chloride and wash with water and charcolise in methanol and finally dry product

Apripitatnt

Route of Synthesis:

85

Material Balance

Sr.

No Input Material Kg Output Material Kg

1

2-{1-[3,5-

Bis(trifluoromethyl)phenyl]ethoxy

}-3-(4-fluorophenyl)morpholine

hydrochloride

1.00 Apripitatant

0.9

2 Amidrazone 1.15 O-xylene 6

3 Potassium carbonate 3.50 DMF CF ML 4.1

4 Dimethyal formamide 2.5 Methanol CF ML 6.8

5 O-xylene 6.4 Charcoal Solid waste 0.54

6 Sodium chloride 0.45 Aq. Effluent 20.18

7 Methanol 6.0 Drying loss 0.4

8 Activated charcoal 0.22 Process emission 0.3

8 Purified water 18.0


86

ANNEXURE - IV

WATER CONSUMPTION & WASTEWATER GENERATION

Proposed

Sr. No. Category Proposed Scenario (m

3/day)

Water Consumption Waste Water Generation

1 Industrial

Process 28 33

Boiler 15 1.5

Cooling 5 0.5

Washing 2 1.5

Scrubber 2 2.7

2 Gardening 1.5 --

3 Domestic 2 1.2

4 R&D 0.026 0.025

Total (Industrial) 52 39.2

Total 55.526 40.425

Note:

- Total water requirement will be 55.526 KLD. Fresh water requirement will be 21.526 KLD.

Total 34 KLD will be reused within premises.

- MEE Condensate of 19 KLD will be reuse in boiler.

- RO permeate of 21 KLD will be reused in boiler.

- All domestic wastewater will be sent to Septic Tank & Soak Pit.

87

WATER BALANCE DIAGRAM

Total 55.526 KLD (Fresh Water: 21.526 KLD +

Reuse: 34 KLD)

Domestic: 2

KLD

Process: 28

KLD (Reuse:

21 + Fresh: 7)

Boiler:

15 KLD

(Reuse:

13 +

Fresh: 2)

Cooli

ng

Towe

r: 5

KLD

Wash

ing: 2

KLD

Gardeni

ng: 1.5

KLD

33 KLD

1.5

KLD 0.5 KLD 1.5 KLD

Soak Pit/

Septic Tank:

1.6 KLD

ETP: 26.525 KLD

RO: 26.525 KLD

Scrubber:

2 KLD

Scrubber: 1.4 KLD of

Dil. HCl will be reused

in Mfg. process.

Excess Qty. sold

under rule-9

permission.

Scrubber: 1.3 KLD of

Sodium sulphite will

be sold under rule-9

permission

Reject: 5.525 sent to

MEE

10 KLD (High COD & TDS)

+ 5.525 KLD (RO Reject) =

15.525 KLD MEE +

Stripper

23 KLD

(Low COD

& TDS)

Permeate: 21 KLD

reused in Boiler

Solvent Stripper

Solvent

Residue: 0.8

KLD

MEE: 14.725 KLD

Condensate:

13 KLD reused

in Boiler

MEE Salt: 1.5

MT/Day

Loss:

0.225

KLD

R&D:

0.026

KLD

0.0

25

KLD

88

ANNEXURE - V

EFFLUENT TREATMET PLANT DETAILS:

M/s. Krufren Pharma shall have an Effluent treatment plant consisting of primary, secondary,

tertiary treatment and advance treatment units. The details of up gradation ETP are as follows.

Stream I (RAW EFFLUENT Stream) (26.5 KLD)

DETAILS OF EFFLUENT TREATMENT PLANT (PROPOSED)

First all streams of wastewater shall be passed through O & G Trap (OGT-01) where O & G shall

be removed from the Top manually and Collected in O & G Collection Tank (OGCT-01) then

effluent will be collected in Equalization cum Neutralization Tank-1 (ENT-01) where the addition

and stirring of Acid/Alkali shall be done to maintain neutral pH of wastewater from Acid/Alkali

Dosing Tanks (ACDT-01/ALDT-01) as per requirement. Mixer is provided in ENT-01 for proper

mixing and prevents the settling of suspended solids.

Then after, neutralized wastewater shall be pumped to Flash Mixer (FM-01) where the

continuous addition and stirring of Alum solution is from Alum Dosing Tanks (ADT-01-A/B) as per

requirement. Then Polyelectrolyte shall be dosed from Polyelectrolyte Dosing Tank (PEDT-01) to

carry out flocculation with help of Mixer Mechanism. Then after, coagulated wastewater shall be

settled in Primary Settling Tank-1 (PST-01).

Clear supernatant from PST-01 shall be passed in Aeration Tank(AT-01). Here, biodegradation of

organic matter of the wastewater shall be carried out by bacteria (suspended growth) in the AT-

01 and for that oxygen shall be supplied by 2 nos. of air blowers through diffusers. Air blowers

also keep MLSS in suspension.

Then after, wastewater shall go to Secondary Settling Tank (SST-01). Here, the suspended solids

shall be settled. Sludge shall be removed from bottom of SST-01 and pumped to AT-1 to

maintain MLSS and excess activated sludge shall be sent to Sludge Drying Beds(SDB-01).

Clear supernatant from SST-02 shall be collected in Intermediate Sump (IS-01) by gravity.

Thereafter, the wastewater shall be passed through Pressure Sand Filter (PSF-01) to remove left

out TSS and Activated Carbon Filter (ACF-01) for final effluent polishing. After tertiary treatment,

effluent shall be collected in Treated Effluent Tank (TET-01) before passed through RO Unit (RO-

01) for advance treatment. RO permeate shall be collected in RO Permeate Tank (ROPT-01)

before reuse in plant and RO reject shall sent to MEE Feed Tank (MFT-01) for further treatment.

89

Sludge settled in PST-01 and excess sludge from SST-01 shall be sent to Sludge Beds (SDB-01) for

sludge dewatering. Then, dewatered sludge shall be stored in HWSA and then ultimate disposal

to TSDF. Leachate from SDB-01 and backwash from PSF-01 and ACF-01 shall be sent back to ENT-

01 for further treatment.

Stream II (High TDS stream) (10 KLD)

All High TDS streams of wastewater shall be collected in Equalization cum Neutralization Tank-2

(ENT-02).where Alkaline Lime shall be added from Alkali Dosing tank. Then after, effluent shall

have sent to Primary Settling Tank-2 (PST-02) where Alum and poly shall be added from ADT and

PDT-01 respectively. Mixer is provided in PST for Mixing of chemicals. Then Mixer will be

stopped and solids are allowed to settle at bottom.

Clear effluent from PCL-02 shall be collected in Holding Tank-1 (HT-01) before pumped to

strippers (ST-01) for removal of solvent. Effluent from stripper collected in MEE Feed Tank (MFT-

01). Then effluent shall be sent to Multiple Effect Evaporator (MEE-01) for further treatment

followed by Solid Dryer (SD-01) for solids dewatering. Condensate from MEE-01&SD-01 shall

collect in ME Condensate Tank (MECT-01) before reuse in utilities. Solids from SD-01 shall be

collected and stored in HWSA for disposal in TSDF.

Details of ETP Units: 26.5 KLD

Sr.

No. Name of Unit Tag No.

Size in Meters

(L X B X (LD+FB) Nos. MOC

1. Oil & Grease Tarp-01 OGT-01 3.0 x 0.7x (1.5+0.5) 1 RCC M30+ A/A

res. Lining

2. Oil & Grease Collection

Tank-01 OGCT-01 500 Lit 1 HDPE

3. Equalization cum

Neutralization Tank-1 ENT-01 4.0 x 3.0 x (2.5+0.5) 1

RCC M30+ A/A

res. Lining

4. Flash Mixer FM-01 1.0 x 1.0 (2.0+0.5) 1 RCC M30

5. Primary Settling Tank-1 PST-01 3.0 x 1.5 x (2.0+0.5) 1 RCC M30

6. Aeration Tank AT-01 6.0 x4.0 (4.0+0.5) 1 RCC M30

7. Secondary Settling Tank SST-01 3.0 x 1.5 x (2.5+0.5) 1 RCC M30

8. Intermediate Sump IS-01 2.0 x 1.5 (2.5+0.3) 1 RCC M30

9. Pressure Sand Filter PSF-01 30 M3/D 1 MSEP

10. Active Carbon Filter ACF-01 30 M3/D 1 MSEP

11. Treated Effluent Tank TET-01 4.0 x 3.0 x (2.5+0.5) 1 RCC M30

13. Sludge Drying Beds SDBs-01-A/B 4.0 x 3.0 3 RCC M30

14. RO Unit RO-01 30 KLD 1 As per Std.

90

15. RO permeate Tank ROPT-01 5 KLD 1 HDPE

16. Acid Dosing Tank ACDT-01 1000 Lit 1 HDPE

17. Alkali Dosing Tank ALDT-01 1500 Lit 1 HDPE

18. Alum Dosing Tank ADT-01 1000 Lit 1 HDPE

19. Poly Dosing Tank PEDT-01 500 Lit 1 HDPE

20. Nutrient Dosing Tank NDT-01 500 Lit 1 HDPE

DETAILS OF UNITS: (FOR HIGH COD & TDS STREAMS) (10 KLD )

Sr.

No. Name of Unit Tag No.

Size in Meters

(L X B X (LD+FB) Nos. MOC

1. Equalization cum

Neutralization Tank-2 ENT-02 3.0 x 2.0 (2.0 + 0.5) 1

RCC M30+ A/A

Bk. Lining

2. Primary Settling Tank -2 PST-02 2.0 x 2.0 x (2.5 + 0.5) 1 RCC M30

3. Holding Tank HT-01 2.0 x 2.0 x (2.5+0.3) 1 RCC M30

4. Stripper ST-01 10 KLD 1 SS316L

5. MEE Feed Tank MFT-01 2.0 x 2.0 x (3.0 SWD +

0.5) 1 RCC M30

6. Multi Effect Evaporator

(MEE-01) with Solid

Dryer (SD-01)

MEE-01/SD-

01 20KLD 1 SS316L

7. Condensate Storage

Tank CST-01 2000 Lit 1 HDPE

CHARACTERISTICS OF WASTEWATER BEFORE & AFTER TREATEMENT

Sr.

No. Parameter

Characteristics (mg/L)

Untreated Final Treated

1. pH 6.0-8.0 7.0-7.5

2. TDS 27,000 500

3. COD 25,000 200

4. BOD3 7,000 50

5. Ammonical Nitrogen 80 10

91

BLOCK DIAGRAM FOR EFFLUENT TREATMENT PLANT

92

ANNEXURE-VI

DETAILS OF HAZARDOUS WASTE GENERATION & DISPOSAL

Sr.

No. Type Of Waste Category

Quantity

(MT/Month)

Source of

Generation

Mode of Treatment

and Disposal

1 Sodium sulphate Schedule-

(I)-(28.1) 4.77

Topiramate

Process

Collection, Storage,

Transportation and

Sell to end users

Having permission

Rule-9 2 Sodium chloride

Schedule-

(I)-(28.1) 6.19

Ropivacine

Process

3 Process Waste Schedule-

(I)-(28.1) 3.13

Glibenclamide

Process


Transportation and

Disposal at common

TSDF Site.

4 ETP Sludge Schedule-

(I)-(35.3) 7.0 ETP Treatment


Transportation and

Disposal to TSDF site.

5

Discarded

Drums/Container

s/Bags

Schedule-

(I)-(33.1) 240

Raw Material

and Storage


Decontamination,

Reuse, Transportation

and sale to authorized

vendor.

6 Used Oil Schedule-

(I)-(5.1) 0.8

From Moving

Machineries


Transportation, Reuse

and sale to authorized

recycles.

7 Spent carbon Schedule-

(I)-(28.3) 2.0

Ropivacaine

Process


Transportation and


8 Spent Solvent Schedule-

(I)-(28.6) 760

Flucanozole

Process


Transportation and

sale to authorized

users.

9 Distillation

Residue

Schedule-

(I)-(20.3) 33 Distillation plant


Transportation and

sent for co-

processing in cement

industries or sent to

common incineration

of M/s. BEIL.

10 Dil. HCl (30%) Sch-(II)-B15 42 Scrubber

Collection, storage

and reuse in

Zonisamide process

(Reqd. qty 75

MT/Month) excess

quantity will be sell to

93

end users having rule-

9 permission.

11 Sodium Sulphite

(28%) Sch-(II)-B36 39 Scrubber


Transportation and

Sell to end users

Having permission

Rule-9

12 Salt from MEE Schedule-

(I)-(35.3) 15 MEE Process


Transportation and


94

ANNEXURE-VII

DETAILS OF STACK AND VENTS

Proposed Flue Gas Emission

Stack

no.

Stack

attached to

Fuel used & rate

of consumption

Stack

height

(m)

Parameters Permissible limits

1 Boiler (2.0

TPH)

Briquettes of Bio

Coal/Coal (1900

MT/Day)

30 SPM

SO2

NOx

Multi-cyclone separator

with bag filter

2 Thermo Pack

(1.0 lakhs

kcal/hr)

Briquettes of Bio

Coal/Coal (1900

MT/Day) or

Hi therm oil (100

Kl/Hr)

30 SPM

SO2

NOx

Multi-cyclone separator

with bag filter

3 D. G Set HSD (50 lit/day) 11 SPM

SO2

NOx

Adequate Stack Height

Proposed Process gas Emission

Sr.

No.

Source of

Emission

Vent (meter) Type of

Emission

APCE

Height Diameter

1 Process Vent

(Chlorination)

11 0.1 HCl Two stage Water scrubber

2 Process Vent

(Sulphonation)

11 0.1 SO2

Two stage Water + Alkali scrubber

95

ANNEXURE-VIII

STORAGE DETAILS OF HAZARDOUS CHEMICALS

SR.

NO

NAME OF THE MATERIAL TYPE OF

HAZARD

NUMBER OF

TANKS/CYLINDERS

MAXIMUMA QTY

TO STORE

1 HYDROGEN GAS FLAMMABLE 10 CYLINDERS 20 CYLINDERS

2 AMMONIA GAS CORROSIVE 04 CYLINDERS 04 CYLINDERS

3 CHLORINE GAS TOXIC 02 CYLINDERS 02 CYLINDERS

4 EDC TOXIC 01 TANK 5.0 KL

5 TOLUENE FLAMMABLE 01 TANK 5.0 KL

6 METHANOL FLAMMABLE 01 TANK 7.0 KL

7 ETHYL ACETATE FLAMMABLE 01 TANK 5.0 KL

8 ACETONE FLAMMABLE 01 TANK 5.0 KL

9 IPA TOXIC 01 TANK 5.0 KL

10 XYLENE FLAMMABLE 01 TANK 5.0 KL

11 MDC TOXIC 01 TANK 5.0 KL

96

ANNEXURE-IX

___________________________________________________________________________

SOCIO - ECONOMIC IMPACTS

1) EMPLOYMENT OPPORTUNITIES

The manpower requirement for the proposed project is being expected to generate some

permanent jobs and secondary jobs for the operation and maintenance of plant. This will

increase direct / indirect employment opportunities and ancillary business development to some

extent for the local population.

This phase is expected to create a beneficial impact on the local socio-economic environment.

2) INDUSTRIES

Required raw materials and skilled and unskilled laborers will be utilized maximum from the

local area. The increasing industrial activity will boost the commercial and economical status of

the locality, to some extent.

3) PUBLIC HEALTH

The company regularly examines, inspects and tests its emission from sources to make sure that

the emission is below the permissible limit. Hence, there will not be any significant change in the

status of sanitation and the community health of the area, as sufficient measures have been

taken and proposed under the EMP.

4) TRANSPORTATION AND COMMUNICATION

Since the existing factory is having proper linkage for the transport and communication, the

development of this project will not cause any additional impact.

In brief, as a result of the proposed project there will be no adverse impact on sanitation,

communication and community health, as sufficient measures have been proposed to be taken

under the EMP. The proposed project is not expected to make any significant change in the

existing status of the socio - economic environment of this region.

97

ANNEXURE-X

___________________________________________________________________

PROPOSED TERMS OF REFERENCE FOR EIA STUDIES

1. Project Description

• Justification of project.

• Promoters and their back ground

• Project site location along with site map of 5 km area and site details providing various

industries, surface water bodies, forests etc.

• Project cost

• Project location and Plant layout.

• Existing infrastructure facilities

• Water source and utilization including proposed water balance.

• List of Products and their capacity

• List of hazardous chemicals with their toxicity levels.

• Mass balance of each product along with the batch size

• Storage and Transportation of raw materials and products.

2. Description of the Environment and Baseline Data Collection

• Micrometeorological data for wind speed, direction, temperature, humidity and rainfall in 5

km area.

• Study of Data from secondary sources.

• Existing environmental status Vis a Vis air, water, noise, soil in 5 km area from the project site.

For SPM, RSPM, SO2, NOx.

• Ground water quality at 5 locations within 5 km.

• Complete water balance

3. Socio Economic Data

• Existing socio-economic status, land use pattern and infrastructure facilities available in the

study area were surveyed.

4. Impacts Identification and Mitigatory Measures.

• Impact on air and mitigation measures including green belt

• Impact on water environment and mitigation measures

• Soil pollution source and mitigation measures

• Noise generation and control.

• Solid waste quantification and disposal.

• Control of fugitive emissions

5. Environmental Management Plan

• Details of pollution control measures

• Environment management team

• Proposed schedule for environmental monitoring including post project

98

6. Risk Assessment

• Details on storage facilities

• Identification of hazards

• Consequence analysis

• Recommendations on the basis of risk assessment done

• Disaster Management Plan.

7. Information for Control of Fugitive Emissions

8. Post Project Monitoring Plan for Air, Water, Soil and Noise.

9. Occupational Health and Safety Program for the Project.

99

ANNEXURE-XI

TOPOSHEET

100

ANNEXURE-XII

GIDC PLOT ALLOTMENT LETTER

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