rpg lifesciences ltd. change in product mix for … · m/s rpg life sciences ltd. proposed project...

M/S RPG LIFE SCIENCES LTD.

Proposed project for modernization with change in product mix of Active

pharmaceutical Ingredients

Plot No.: 25, MIDC Land, Thane-Belapur Road, Pawne, Navi Mumbai -400703,

Maharashtra Pre-Feasibility Report

PFR for M/s. RPG Life Sciences Ltd. Prepared by Goldfinch Engineering Systems Pvt. Ltd.

RPG LIFESCIENCES LTD.

PFR for Environmental Clearance (EC) of proposed project for modernization with

change in product mix for manufacturing of Active Pharmaceutical Ingredients (API) at

existing unit, Plot No.: 25, MIDC Land, Thane-Belapur Road, Navi Mumbai 400703,

Maharashtra.

© Goldfinch Environmental Engineering Systems Private Limited („Goldfinch‟), May 2017

This report is released for the use of the M/s. RPG Life Sciences Ltd. Regulators and relevant

stakeholders solely as part of the subject EC of Proposed project for modernization with change

in product mix for manufacturing of Active Pharmaceutical Ingredients (API) at existing unit, Plot

No.: 25, MIDC Land, Thane – Belapur Road, Pawne, Navi Mumbai 400703, Maharashtra.

Information provided (unless attributed to referenced third parties) is otherwise copyrighted and

shall not be used for any other purpose without the written consent of Goldfinch/RPG.

QUALITY CONTROL

Name of

Publication

RPG Lifesciences Ltd. proposed project for modernization with change in

product mix for manufacturing of Active Pharmaceutical Ingredients (API) at

existing unit Plot No.: 25, MIDC Land, Thane-Belapur Road, Pawne, Navi

Mumbai 400703, Maharashtra

Project Number Report No. 1 Version 1 Released June 2017

Prepared By Mr. Siddhesh Karangutkar & Ms. Reena Jadhav

Reviewed By Dr. Nivedita Kulkarni

Released By Mr. Anand Apte

DISCLAIMER

Goldfinch has taken all reasonable precautions in the preparation of this report as per its

auditable quality plan. Goldfinch also believes that the facts presented in the report are based on

information submitted by RPG Lifesciences and based on the technical expertise of Goldfinch as

on the date it was written. However, it is impossible to dismiss absolutely, the possibility of

errors or omissions. Goldfinch therefore specifically disclaims any liability resulting from the use

or application of the information contained in this report. The information is not intended to

serve as legal advice related to the individual situation.







CONTENTS

1.0 INTRODUCTION OF THE PROJECT .......................................................... 7

1.1 Introduction of the Project ................................................................................................................. 7

1.2 Introduction of the Project Proponent ............................................................................................... 7

1.3 Brief description of nature of the project ........................................................................................... 8

1.4 Need for the project and its importance to the country and or region .............................................. 8

1.5 Demands-Supply Gap .......................................................................................................................... 8

1.6 Imports vs. Indigenous Production ..................................................................................................... 8

1.7 Domestic /Export Markets .................................................................................................................. 9

1.8 Employment Generation due to the project ...................................................................................... 9

2.0 PROJECT DESCRIPTION ....................................................................... 10

2.1 Type of Project ................................................................................................................................. 10

2.2 Project Location ................................................................................................................................ 10

2.3 Details of alternate sites considered and the basis of selecting the proposed site ......................... 13

2.4 Size or Magnitude of Operation .................................................................................................... 16

2.6 Raw material required along with estimated quantity, likely source, marketing area of final

Product/s, mode of transport of raw material and finished product ......................................................... 187

Raw Materials: ............................................................................................. 187

Source for Raw Material Procurement: .......................................................... 187

2.7 Resource optimization/recycling and reuse envisaged in the project ............................................ 191

2.8 Availability of water its source, energy/power requirement and source ....................................... 191

2.8.1 Water Requirement and Source ............................................................................................... 191

2.8.3 Fuel Requirement ............................................................................................................................... 192

2.9 Quantity of wastes to be generated (liquid and solid) and scheme for their management/disposal

192

2.9.2 Effluent ............................................................................................................................................. 194

3.1 Connectivity .................................................................................................................................... 201

3.2 Land Form, Land use and Land ownership .................................................................................... 201

3.3 Topography ................................................................................................................................... 201

3.5 Soil classification ............................................................................................................................ 203

3.6 Climatic data from secondary sources ......................................................................................... 203

Climate Classification .................................................................................................................................. 203

3.7 Social Infrastructure Availability ................................................................................................... 203







4.0 Planning In Brief ............................................................................ 204

4.1 Planning Concept ........................................................................................................................... 204

4.2 Land Use Planning ........................................................................................................................... 204

4.3 Assessment of Infrastructure Demand (Physical & Social) ............................................................. 205

4.4 Amenities/Facilities ......................................................................................................................... 205

4.5 Population Projection ..................................................................................................................... 205

5.0 Existing infrastructure ..................................................................... 206

5.1 Industrial area ....................................................................................................................................... 206

5.2 Residential Area .............................................................................................................................. 206

5.4 Social Infrastructure ....................................................................................................................... 206

5.6 Drinking Water Management ......................................................................................................... 207

5.7 Sewage System ............................................................................................................................... 207

5.8 Industrial Water Management ....................................................................................................... 207

5.9 Solid Waste Management ............................................................................................................. 207

5.10 Power Requirement & Supply / source ................................................................................... 207

6.0 Rehabilitation and Resettlement (R & R) Plan ................................. 208

6.1 Policy to be adopted (Central/State) in respect of the project affected persons .......................... 208

including home oustees, land oustees and landless. .................................................................................. 208

7.0 PROJECT SCHEDULE & COST ESTIMATES ............................................ 209

7.1 Likely date of start of construction and likely date of completion ................................................. 209

7.2 Estimated project cost along with analysis in terms of economic viability of the ......................... 209

project ......................................................................................................................................................... 209

7.3 Economic Viability ........................................................................... 209

8.0 ANALYSIS OF PROPOSAL (FINAL RECOMMENDATIONS) .................. 210

ANNEXURE I – PLANT LAY OUT……………………………………………………209







LIST OF FIGURES

Figure 2-1: Satellite Image of the Site ..................................................... 11

Figure 2-2: RPG Plot on RPG MIDC plan ................................................... 12

Figure 2-3: Site Photographs .................................................................. 14

Figure 3-1: Topograph ........................................................................ 203

LIST OF TABLES

Table 1-1 List of Directors and their designations-------------------------------07

Table 2-1: Existing and Proposed Production Capacity ............................... 16

Table 2-3: Details of Raw material Quantity, Source and Mode of Transport 188

Table 2-4: Details of Raw water consumption.......................................... 191

Table 2-5: Details of emissions from process and flue gas ....................... 193

Table 2-6: Details Stacks along with their mitigation method ................... 194

Table 2-7: Details of Effluent Generation ................................................ 194

Table 2-8: Design details and Performance Projection of ETP ................... 195

Table 2-9: Details of Hazardous Solid waste along with the Category and disposal

method ............................................................................. 198

Table 4-1: Land Use Break Up .............................................................. 204

Table 7-1: Cost Break-Up ..................................................................... 209







EXECUTIVE SUMMARY

RPG Life Sciences, formerly Searle India Ltd, started in 1968 as a joint venture with GD Searle,

USA. In 1999, the company‟s name was changed to RPG Life Sciences Ltd.

RPG Life Sciences, a part of RPG Enterprises, is an integrated pharmaceutical company operating

in the domestic and international markets in the Branded Formulations, Global Generics and

Synthetic APIs space. The company is a research based, pharmaceutical company, producing a

wide range of quality, affordable medicines. Apart from serving the domestic market, the

company is continuously exploring new geographies. To take its products across the globe, the

company currently has several tie-ups with international partners and values these collaborations

greatly. It is always on the look-out for win-win licensing and outsourcing agreements.

The proposed project falls under classification 5(f) of schedules listed in EIA notification SO1533

dated 14/09/2006. Its appraisal category is B.

Project Synopsis:

Sr.

No Parameters Description

1. Category as per EIA

Notification 5 (f ) B

2. Latitude 19.087864° N

3. Longitude 73.018340° E

4. Proposed Production

Capacity

Existing Capacity = 5.88 TPM

Proposed Change in product mix Capacity: 70.56 TPA

5. Total Plot Area 34483 sq. m.

6. Green Belt Area Existing 12414 sq. m

7. Fresh Water

Requirement

Existing water requirement : 350 CMD

No additional water required for change in product mix activity

8. Effluent Quantity

(Trade + Domestic)

Trade Effluent: 120 CMD,

Domestic: Existing: 60 CMD

No change in wastewater generation after proposed change in

product mix

9. Trade Effluent

Treatment

Existing effluent is treated in conventional ETP having Primary,

Secondary and Tertiary treatment having Capacity 200 CMD.

Treated effluent sent to CETP after meeting disposal norms set by

MPCB.







Sr.

No Parameters Description

10. Domestic Waste water

Treatment Septic tank followed by combined treatment in ETP

11. Fuel requirement at full

load

Equipment Fuel Quantity required at

full load

Existing Boiler

1 No 2 TPH PNG/FO (Optional)

41.6 SCM/hr. or

41.6 Kg/hr.

Existing D G

1 no X 625

KVA

HSD 104 Kg/hr.

12. Power Requirement Existing power (Connected load)= 2975 KW

No additional power required

13. Dispersion of emission

for Boiler Stack Height : 33.3 m

14. Dispersion of emission

DG Sets,

D.G Set X 1 No. = 625 KVA

Stack Height: 10 m

15. Work Force

Existing: Permanent 330 + Contract 70 = 400 workers

No extra man power is required for modernization.

16. Total Capital Cost the

project Capital Cost: 81.10 Crs







1.0 INTRODUCTION OF THE PROJECT

1.1 Introduction of the Project

RPG Lifesciences Ltd. (Hereafter being referred as RPG for brevity in this text) proposed project

for modernization with change in product mix to manufacture of Active Pharmaceutical

Ingredients (API).

RPG Life Sciences, a part of RPG Enterprises, is an integrated pharmaceutical company operating

in the domestic and international markets in the Branded Formulations, Global Generics and

Synthetic APIs space. The company is a research based, pharmaceutical company, producing a

wide range of quality, affordable medicines. Its brands are highly trusted by healthcare

professionals and patients. Customer satisfaction is fundamental to the company. With

manufacturing facilities located in Ankleshwar, Gujarat and Navi Mumbai, Maharashtra, RPG Life

Sciences is a company that is growing from strength to strength to capture the enormous

opportunities that the pharmaceutical space offers. These facilities have been approved by

various regulatory bodies.

The proposed modernization project is in TTC MIDC; which is approved chemical manufacturing

zone of MIDC. RPG Life Sciences Ltd. is located at plot no. 25 to manufacture API having existing

capacity of 5.88 TPM and after modernization capacity will be 70.56 TPA (5.88 TPM).

As per the EIA Notification S.O. 1533 dated 14th September 2006, proposed activity is covered

under Synthetic Organic Chemical Industry 5 (f) and needs prior environmental clearance.

Further, as the proposed industry is under category B. Since it is located in a notified industrial

area the project will not need public approval and is under category B1.

1.2 Introduction of the Project Proponent

List of directors along with their designation is given in Table 1-1

Table 1-1: List of Directors and their designations

Mr. Harsh Vardhan Goenka Chairman & Non-Executive Director

Mr. C.L. Jain Independent and Non-Executive Director

Dr. Lalit Kanodia Independent and Non-Executive Director

Mr. Mahesh Gupta Independent and Non-Executive Director

Mr. Manoj Kumar Maheshwari Independent and Non-Executive Director







Mr. Pradipta Kumar Mohapatra Independent and Non-Executive Director

Mr. Narendra Ambwani Independent and Non-Executive Director

Ms. Zahabiya Khorakiwala Independent and Non-Executive Director

Mr. Yugal Sikri Independent and Non-Executive Director

Mr. Sachin Nandgaonkar Non-Executive Director

Mr. CT. Renganathan Managing Director

1.3 Brief description of nature of the project

The proposed modernization with change in product mix will be carried out at existing

manufacturing unit located at Plot No. 25 at MIDC Land, Thane-Belapur Road, Pawne, Navi

Mumbai, with land admeasuring 34483 Sq. Meters. After proposed change in product mix

total production capacity will remain same, i.e. 5.88 TPM however the production

capacity will get change from Ton per month to Ton per Annum which will become

70.56 TPA.

1.4 Need for the project and its importance to the country and or region

Industrialization in India is increasing at rapid pace and is leading to growth and expansion of

various industries like Pharmaceuticals, agrochemicals etc. M/S RPG Life sciences Ltd. is a global

supplier of API (Bulk drug and intermediate) to the pharmaceutical industries, among others. RPG

aims to expand its horizons further in India and abroad by modernization its capacities. These

products will serve to cut the supply of imports from foreign countries thus saving currency and

at the same time will earn valuable foreign currency by export of products.

1.5 Demands-Supply Gap

Competition in the Indian Pharmaceutical market swelled in recent years, with increasing generic

penetration. This had many companies opting out of low-margin segments, as competition

resulted in lower prices. This created a gap between demand and supply. Such unusual price

hikes take place when there is withdrawal of some of the key competitors, which leads to demand

override and as a consequence prices start soaring in a free-pricing market.

1.6 Imports vs. Indigenous Production

The rising demand for API and has also given rise to competition from foreign players. The

proposed modernization will also help check the competition from foreign players







1.7 Domestic /Export Markets

The finished goods will be sold in domestic market and would be largely exported to the

Regulated International Market as per demand all over the world.

1.8 Employment Generation due to the project

The proposed modernization process does not required extra manpower. Existing manpower

will be utilized for proposed modernization.







2.0 PROJECT DESCRIPTION

2.1 Type of Project

Proposed project is for modernization with change in product mix to manufacture of API

falling in category 5(f) B-1 of EIA notification 2006. The existing capacity of products 5.88 TPM

and after modernization it will be 70.56 TPA (5.88 TPM).

2.2 Project Location

RPG Life Sciences Ltd. project manufacturing unit at Plot No. 25/25A, MIDC Land, Thane-Belapur

Road, Pawne, Navi Mumbai, State - Maharashtra. Major factories adjacent to the manufacturing

unit are Savita Chemicals on South, Zydus Takeda on North side, NOCIL Ltd. On East. The

proposed site is well connected by road to Thane Belapur Road which connects to Mumbai Goa

and Mumbai Bangalore highway. Nearest railway station is at Turbhe 1 km and Thane Railway

station which is 15 Km away from site. The nearest airport is at Mumbai at 30 km.







Figure 2-1 : Satelite Image of the Site

Corner Latitude Longitude

A 19.086933° 73.017683°

B 19.086782° 73.018998°

C 19.088476° 73.019082°

D 19.089067° 73.017883°

center 19.087864° 73.018340°







Figure 2-2 : TTC MIDC Map







The project site is situated in TTC MIDC. It is a notified industrial area where the land is

owned by Maharashtra Industrial Development Corporation (MIDC) and leased to the

Company. The land is meant for industrial activity.

Land Ownership: Land is owned by Maharashtra Industrial Development Corporation

(MIDC) and leased to the Company for 99 years.

2.3 Details of alternate sites considered and the basis of selecting the proposed site

The proposal is for modernization in same products at the same manufacturing unit using

existing infrastructure only hence consideration of alternate site is not done.







Figure 2.3: Site Photograph

Green Belt Area







Manufacturing Unit

Effluent Treatment Plant







2.4 Size or Magnitude of Operation

The products manufactured and their capacities proposed are shown in below Table

2.1

Table 2-1: List of Products

Sr.

No

.

Existing Product

Existing

Quantity

in MT/M

Proposed

Change in

Product Mix Proposed

Quantity

(MT/A) Deleted/

Added

1 Diuretic 1 Spironolactone

etc. 0.3333

0

70.56

2 Anti-Psychotic

1 Haloperidol etc.

0.35

2 Haloperidol

Decanoate etc.

3 Risperidone etc.

4 Olanzapine etc. 0

5 Aripiprazole etc. 0

6

Quetiapine

Hemifumarate

etc.

0

3 Anti-Arrhythmic

class I 1

Disopyramide

Phosphate etc. 0.0125

4 Anti-Emetic 1 Dimenhydrinate

etc. 0.0100

0

5 Anti-Diarrhoeal 1 Diphenoxylate

HCL etc. 1.0000

6 Immunosuppressa

nt

1 Azathioprine etc.

1.6667

2 Mycophenolate

Mofetil etc.

3 Mycophenolate

Sodium etc.

4 Fingolimod etc. 0

7 Collinergic

Blockers 1

Propantheline

Bromide etc. 0.1000

8 Anthelmentic 1 Quinfamide etc. 0.1667

9

Anti-

Thrombotic/Anti-

Platelet

1 Clopidogrel

Bisulphate etc.

1.1250

2 Clopidogrel

Besylate etc.

3 Ticlopidine HCL

etc.

10 Anti-Convusant 1 Lamotrigine etc. 0.1250

11 Anti-Depressant

1 Sertraline HCL

etc. 0.0525

2 Escitalopram

oxalate etc.

0

12 Anti-Anginal 1 Nicorandil etc. 0.5000







2 Ivabradin HCL

etc.

0

13 Anti-Alzheimer 1 Donepezil etc. 0.0167 0

14 Anti-Hypertensive

1 Tolvaptan etc

0.1250

2 Benidipine.HCl

etc.

3 Solifenacin etc.

4 Irbesartan etc. 0

5 Lercanidipine

HCL etc.

0

6 Eplirenone etc 0

7 Candisartan

celextil etc.

0

8 Conivaptan etc. 0

15 Anti-Migrane 1 Eletriptan Etc. 0.0167 0

16 Anti-Gout 1 Febuxostat Etc. 0.0167 0

17 Anti-Obesity 1 Orlistate Etc. 0.0467 0

18 Anti-Viral 1 Tamiflu Etc. 0.0167 0

19 Anti-Ulcerant

1

Pantaprazole

Sequehydrate

etc. 0.2000

2 Lafutidine etc. 0

3 Pantaprazole

Sodium etc 0

Added

20 Anti-

Hyperparathyroid 1 Cinacalcet.HCl etc. 0

Added

TOTAL 5.88

MTM

70.56

MTA

RPGLS shall manufacture any 15 products at a time on campaign basis.

After proposed change in product mix total production capacity will remain same, i.e.

5.88 TPM however the production capacity will get change from Ton per month to Ton

per Annum which will be 70.56 TPA.







2.5 PROCESS DESCRIPTION:

1) HALOPERIDOL

Process Description:

Step-1: - Chloro Butyroyl Chloride

γ- Butyrolactone and anhydrous Zinc Chloride are mixed and later reacted with Thionyl

Chloride at refluxing temperature. The Chloro Butyroyl Chloride is collected after

distillation.

Step-2: - Chloro Fluoro Butyro Phenone

Chloro Fluoro Butyro Phenone is synthesized by reacting Chloro Butyroyl Chloride with

Fluoro benzene in presence of Methylene Chloride and anhydrous Aluminium Chloride.

Step-3: - Chloro Fluoro Butyro Phenone Ketal

Chloro Fluoro Butyro Phenone is reacted with Trimethyl Ortho Formate in presence of

Methanol and Sulphuric Acid to give Chloro Fluoro Butyro Phenone Ketal.

Step-4: - Haloperidol HCL

Condensation of 4-(4-chlorophenyl)-4-hydroxy piperidine with 4-chloro-1-(4-

fluorophenyl)-1-butanone ketal in presence of aqueous sodium carbonate. Reflux the

batch for 6 hours. Cool to temperature 80oc to 90oc. This is followed by treatment with

hydrochloric acid to give Haloperidol Hydrochloride.

Step-5: - Haloperidol Crude

Haloperidol Hydrochloride is converted to Haloperidol crude by treatment with ammonia in

toluene. Agitate the batch for one hour at 70-75°C.

Step-6: - Haloperidol

Haloperidol crude is purified using ethyl acetate to give Haloperidol pure.







Stage I CBC (Chloro Butyroyl Chloride)

Butyro Lactone

Vapour Loss

Zinc Chloride Anhydrous Fused

Solid waste

Thionyl Chloride

Low Volatile

Residue

CBC (Chloro Butyroyl Chloride)

Reactor

Reaction:

Flow Diagram:







Stage II CFB

Chloro Butyroyl Chloride

Aluminium Chloride Anhydrous

Flurobenzene

Methylene Dichloride

Reaction Mass

Reaction Mass Aq. Layer

Water


Sodium Sulfate Anhydrous

Reaction Mass

Reaction Mass

Solid waste

Reaction Mass

Reaction Mass

Vapour Loss

Dist. MDC

CFB

Reactor

Reactor

Filter

Reactor







Stage III Chloro Flouro Butyro Phenone Ketal (CFB Ketal)

CFB

Vapour Loss

Tri Methyl Ortho Formate

Methanol Mix Solvent (Dist.)

Sulphuric Acid (CP)

Tri Ethyl Amine

Chloro Flouro Butyro Phenone

Ketal (CFB Ketal)

Reactor







Stage IV Haloperidol Hydrochloride

Sodium Carbonate ML Vapour Loss

CPP Vapour Loss Water Aq Layer

CFB Ketal Caustic Lye Residue

Aq. Layer

Toluene

Dist. Toluene

Water

Reaction Mass

Reaction Mass

Methanol

Hydrochloric Acid CP

Reaction Mass

Reaction Mass

ML

Toluene

water

Haloperidol Hydrochloride

Total

Reactor

Reactor

Reactor

Centrifuge







Stage V Haloperidol Crude

Vapour Loss

Haloperidol HCL ML

Dist . Toluene

Ammonia Solution Vapour Loss

Water Aq. Layer

Toluene

Residue

Water

Total

Reaction Mass

Reaction mass

ML

Water

Wet Cake

Wet cake

Water

Reaction mass

Reaction mass

ML

Wet Cake

Wet cake

Toluene

Reaction mass

Reaction mass

ML

Wet Cake

Wet Cake Vapour Loss

Haloperidol HCl

Reactor

Reactor

Centrifuge

Reactor

Centrifuge

Reactor

Centrifuge

Dryer







Stage VI Haloperidol

ML Vapour Loss

Haloperidol Crude Vapour Loss

Dist . Ethyl Acetate

Activated Charcoal

Ethyl Acetate Reaction Mass

Reaction mass

Reaction Mass ML

Reaction mass Solid waste

Wet Cake

Reaction mass

Wet Cake vapour Loss

Reaction mass Vapour Loss

2nd Crop Haloperidol

Dist. Ethyl Acetate

Reaction mass

Reaction mass ML

Ethyl Acetate

Wet cake

Wet cake Vapour Loss

Dry Haloperidol

Dry Haloperidol Handling Loss

Haloperidol

Centrifuge

Dryer

Cad mill

Reactor

Reactor

Centrifuge

Sparkler Filter

Dryer

Reactor







Material Balance: Per Kg

Stage-1

INPUT OUTPUT

Chemical name kg

Name Kg

CFB 0.86 Product 1.00

CFB ketal Methanol 0.54 As Emission 0.11

Trimethyl ortho formate 1.66 Hazardous

Waste

0.00

Sulphuric acid cp 98% 0.01 effluent

Triethlamine 0.04 Recovered

Solvent

2.01

As moisture

Total 3.12 Total 3.12

Stage 2

INPUT OUTPUT

Chemical name kg Name Kg

Haloperidol

HCL

CPP 0.35 Product 1.00

Stage 1 0.42 As Emission 0.24

Sodium carbonate

anhydrous

0.31 Hazardous

Waste

0.00

Toluene 4.90 effluent 9.06

Methanol 0.33 Recovered

Solvent

4.65

Hydrochloric acid

commercial

0.50 As moisture 0

Caustic soda lye 0.07

Water 8.09

Total 14.96

Total 14.96







Stage3

INPUT OUTPUT

Chemical name kg

Name Kg

HALOPERIDO

L CRUDE

Stage 2 2.37 Product 1.00

Liquor ammonia 0.69 As emission 0.24

Toluene 4.90 Hazardous

Waste

Water 16.45 effluent 18.50

Recovered

Solvent

4.65

As moisture


Stage 4

INPUT OUTPUT



HALOPERIDOL

I.P.

Ethyl acetate 17.81 As Emission 0.89

Activated carbon special

grade

0.06 Hazardous

Waste

0.06

effluent

Recovered

Solvent

16.92

As moisture 0








2) HALOPERIDOL DECANOATE

PROCESS DESCRIPTION:

Step-1: - Decanoyl Chloride

Decanoic acid is reacted with Thionyl chloride to give Decanoyl Chloride.

Step-2: - Haloperidol Decanoyl HCL Crude

Haloperidol pure is reacted with Decanoyl Chloride distilled to yield Haloperidol Decanoyl

HCl crude.

Step-3: - Haloperidol Decanoyl HCL Pure

Haloperidol Decanoyl crude is purified with acetone to give Haloperidol Decanoyl HCl pure.

Step-4: - Haloperidol Decanoate

Haloperidol Decanoyl HCl pure is dissolved in Hexane, charcolised, filtered, distillation

followed by crystallization and then dried to get Haloperidol Decanoate.







CHEMICAL REACTION:







Flow Diagram:

Stage I Decanoyl Chloride Product Code- 1200343

Decanoic Acid Vapour Loss

Thionyl Chloride Distillate

Toluene used for cleaning

Toluene Residue Hazardous waste

Reaction mass

Total

Stage II Haloperidol Deconyl HCl Crude Product Code- 1200344

Haloperidol

Deconyl Chloride Vapour Loss

Dimethyl Formamide

Water

Reaction Mass

Reaction Mass ML

Sale

Water

Wet Cake


Haloperidol Deconyl HCl Crude

Centrifuge

CF1003/

CF1004 (48")

Dryer DR1402

(48 Trays)

Reactor

R-1014

(680 L GLR)

Reactor

R-1008

(1360 L GLR)







Stage III Haloperidol Deconyl HCl Pure Product Code- 1200345

Haloperidol Deconyl HCL Crude ML Vapour Loss

Vapour Loss

Acetone Dist .Acetone

Dist.Acetone

Residue

Reaction Mass

Reaction Mass

ML

Acetone

Wet cake

Vapour Loss

Haloperidol Deconyl HCL Crude

Acetone Dist.Acetone

Reaction mass

Reaction mass

ML

Acetone

Wet cake


Haloperidol Deconyl HCl Pure

ML Recovery

Reactor

R-1008

(1360 L GLR)Reactor

R1008

(1360 L GLR)

Centrifuge

CF1004/

CF1003 (48")

Dryer DR1402

(48 Trays)

Centrifuge

CF1004/

CF1003 (48")

Reactor

R-1008

(1360 L GLR)







Stage IV

Haloperidol Deconyl HCL Pure Vapour Loss

Hexane Aq. Layer

ETPSodium Sulphate anhydrous Hazardous waste

Water

Ammonia solution

Activated Charcoal

Reaction Mass

Reaction Mass Hazardous waste

Hexane

Reaction Mass

Reaction Mass Vapour Loss

DSP/ Acetone

Dist. Hexane

Water ETP

Reaction Mass

Reaction Mass

ML

DSP with Acetone Sale

Water

Wet cake


Dry Haloperidol Decanoate

Dry Haloperidol Decanoate Milling Loss

Milled Haloperidol Decanoate

Milled Haloperidol Decanoate Sifting Loss

Haloperidol Decanoate

Multi Mill

MM1402/

MM1401

Reactor

R-1025

(1000 L SSR)

Sifter SR1101

(30")

Reactor

R-1007

(3600 L SSR)

Centrifuge

CF1009/

CF1010 (48")

DCRVD1401/

DCRVD1402

(1000 L)

Sparkler Filter

SF1011/

SF1014 (14")







Material Balance:

Stage 1

INPUT

OUTPUT

Chemical name kg

Name Kg

CFB 0.86

Product 1.00

CFB ketal Methanol 0.54

As Emission 0.09

Trimethyl ortho formate 1.66

sludge 0.00

Sulphuric acid cp 98% 0.01

effluent

Triethlamine 0.04

Recovered

Solvent

2.03

As moisture

Total 3.12

Total 3.12

Stage 2

INPUT OUTPUT

Chemical name kg

Name

Kg

Haloperidol

HCL

CPP 0.35 Product 1.00

STAGE-1 0.42 As Emission 0.26

Sodium carbonate

anhydrous

0.31 Hazardous

Waste

0.00


Methanol 0.33 Recovered

Solvent

4.96

Hydrochloric acid

commercial

0.50 As moisture 0


Water 8.09

Total 14.96

Total 14.96







Stage3

INPUT

OUTPUT

Chemical name kg

Name Kg

HALOPERID

OL CRUDE

Stage2 2.37

Product 1.00

Liquor ammonia 0.69 As Emission 0.24

Toluene 4.90

Hazardous

Waste


Recovered

Solvent

4.65

As moisture

Total 24.40

Total 24.40

Stage 4

INPUT OUTPUT

Chemical name kg

Name Kg

Stage2 1.10 Product 1.00

HALOPERID

OL I.P.



grade

0.06 Hazardous

Waste

0.06

effluent

Recovered

Solvent

16.92

As moisture 0


Stage5

INPUT OUTPUT

Chemical name kg

Name Kg

Deconoic acid 1.06 Product 1.00

Decanoyl

Chloride Thionyl chloride

0.86 As Emission 0.03

Caustic soda lye

6.96 Hazardous

Waste


Acetone

0.47 Recovered

Solvent

0.54

As moisture 0








Stage6

INPUT OUTPUT

Chemical name kg

Name Kg

HALOPERIDOL

DECONYL HCL

CRUDE

Stage-4 0.76

Product 1.00

Deconyl chloride 0.60

As Emission 0.39

Dimethyl formamide 7.27

Hazardous Waste

Acetone 0.50

effluent 3.78

Water 3.42

Recovered

Solvent 7.38

As moisture 0

Total 12.55

Total 12.55

Stage 7

INPUT

OUTPUT

Chemical name kg

Name Kg

Stage-6 1.18 Product 1.00

Acetone 36.47 As Emission 1.82

Hazardous

Waste

effluent

Recovered

Solvent

34.83

As moisture 0

Total 37.65

Total 37.65







Stage8

INPUT OUTPUT

Chemical name kg

Name Kg


Liquor ammonia 5.70 As Emission 0.75

Activated charcoal

special grade

0.07 Hazardous

Waste

0.32

Sodium sulphate

anhydrous

0.25

Hexane 12.15 effluent 27.25

Denatured absolute

alcohol (5% acetone)

2.77 Recovered

Solvent

14.17

Water 21.19 As moisture 0








3) RISPERIDONE


Step-1: - N-Acetyl INPA

Isonipecotic acid is converted to its N-acetylated derivative by treatment with acetic

anhydride.

Step-2: - RSK Oxime Crude

N-Acetyl isonipecotic acid is reacted with thionyl chloride in EDC and the acid chloride thus

generated is then reacted in-situ with 1, 3-difluorobenzene in presence of Friedl-crafts

catalyst (AlCl3) to form 4-(2, 4-Difluorobenzoyl)-1-acetylpiperidine.

Step-3: - RSK Oxime Pure

RSK-Oxime crude is first refluxed in aq. HCl and the deacetylated product thus generated

is then reacted in-situ with hydroxylamine hydrochloride at pH 5-6 to form (2,4-

Difluorophenyl)-piperidin-4-yl-methanone oxime.

Step-4: - RS Amine

RSK-Oxime (Pure) is cyclised by refluxing with 50% KOH solution to form 6-fluoro-3-(4-

piperidinyl)-1,2-benzisoxazole (RS-Amine).

Step-5: - RSPP

2-Aminopyridine and - Acetyl--butyrolacetone are condensed in the presence of POCl3

to form 3-(2-Chloroethyl)-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one.

Step-6: - RS Chloride

RS-PP is hydrogenated in the presence of 10% Pd/C to form RS-chloride.

Step-7: - Risperidone Crude

RS-chloride is condensed with RS-Amine in the presence of Na2CO3 and water to yield

Risperidone crude

Step-8: - Risperidone Crude Repulp

Risperidone Crude is repulped in Dimethyl Formamide to yield Risperidone Crude Repulp.

Step-9: - Risperidone Pure

Risperidone Crude Repulp is purified by charcoalisation in MDC to yield Risperidone Pure.

Step-10: - Risperidone

Risperidone Pure is repulped in Acetonitrile to yield Risperidone.







REACTION:







Stage I Product Code- 1200329

ML Vapour Loss

Isonipecotic Acid

Vapour loss(Tol.+ Ace.

Anhydride) Water

Acetic Anhydride

Disti.Toluene

Toluene Reaction Mass

Water

Reaction mass

Reaction Mass ML

Reaction mass Wet Cake

ML

Water

Wet cake

Hazardous

Waste Wet Cake vapour Loss

2nd Crop N-Acetyl INPA

Wet cake

Vapour Loss

N-Acetyl INPA

Reactor

Reactor

R-1026 ( 1

KL SSR)

Centrifuge

Centrifuge CF1007

(48")

Dryer

Dryer DR1401

(48 Trays)

FLOW DIAGRAM:







Stage II

N-Acetyl INPA

Vapour Loss(MDC +

Thionyl Chloride)

Methylene Chloride

Dist MDC

1,3 Difluoro Benzene(IMP)

Aluminium Chloride Anhydrous

BTEAC

Thionyl Chloride

Reaction Mass

Reaction Mass

Water Vapour Loss

Conc. Hydrochloric acid Aq.Layer

Methylene Dichloride Dist. MDC

Caustic soda lye

Hydroxylamine HCl

Triethyl amine

Reaction mass

Reaction mass

ML

Water

Absolute alcohol with 5% Acetone

Wet cake


RSK Oxime Crude

Reactor R1031

(1.6 kL GLR)

Reactor R1009

(3.0 kL GLR)

Centrifuge CF1003

(48")

Dryer DR1401

(48 Trays)







Stage III

RSK Oxime Crude ML Vapour Loss

Vapour Loss(Methanol)

Activated carbon Dist Methanol

Methanol

Reaction Mass

Reaction Mass

Reaction Mass ML

Reaction Mass

Hazardous waste

Wet Cake

Reaction Mass

Wet Cake vapour Loss

Reaction Mass Vapour Loss(Methanol)

Dist. Methanol 2nd Crop RSK Oxime Pure

Reaction Mass

Reaction Mass

ML

Wet cake


RSK Oxime Pure

Only Methanol recovery done -residue not isolated and dryed

Reactor

Reactor R1031

(1.6 KL GLR)

Centrifuge

CF1003 (48")

Sparkler Filter

SF1004 (14")

Dryer DR1401

(48 Trays)

Reactor R1009

(3.0 KL GLR)

Centrifuge CF1003

(48")

Dryer DR1401

(48 Trays)







Stage IV

Vapour Loss ML Vapour Loss

Caustic Potash Flakes Emulssion Dist Hexane

ETP

Hexane Dist. Hexane

Reaction Mass

Water Aq.Layer

ETP

Reaction mass


Hexane ML

Wet Cake


RS Amine

Reactor

R1002

(1360 L SSR)Reactor R1002

(1360 L SSR)

Centrifuge CF1001/

CF1008 (36/48")

Dryer DR1401

(48 Trays)

4-(2-4-Difluoro benzoyl

oxime)-piprodine (RSK







Stage V

Alpha Acetyl gamma butyrolactone

2-Amino pyridine Vapour Loss

Phosphorous Oxychloride

Mix Organic layer

Toluene Sale

Water

Caustic soda lye

Reaction Mass

Reaction Mass

ML

Water Sale

Wet cake

Wet cake

Methanol

Reaction mass

Reaction mass

ML(Methanol)

Methanol Sale

Wet cake


RSPP PURE

Centrifuge CF1001/

CF1008 (36/48")

Reactor R1014

(680 L GLR)

Centrifuge CF1001/

CF1008 (36/48")

Reactor R1014

(680 L GLR)

Dryer DR1401

(48 Trays)







Stage VI

RSPP Pure

10% Palladium on charcoal

Hyflo

Water


Hydrogen gas Reaction mass

Reaction mass

Spent Catalyst

Water

RS Chloride

Buckner filter

(BF1001)

Reactor R1001

(630 L GLR)







Stage VII

RS Chloride

RS Amine

Sodium Carbonate

Reaction mass

Total

Reaction mass

ML

Water Sale

Wet cake

Wet cake

Water

Reaction mass

Reaction Mass ML

Sale

Water

Wet cake

Wet cake vapour Loss

Risperidone crude

Reactor R1032

(1000 L SSR)

Centrifuge CF1003/

CF1004 (48")

Reactor R1032

(1000 L SSR)

Centrifuge CF1003/

CF1004 (48")

Dryer DR1402

(48 Trays)







Stage VIII Risperidone Crude Repulp

Risperidone Crude

Dimethyl Formamide

Reaction mass

Reaction mass

ML

Dimethyl Formamide Sale

Wet cake

wet cake Vapour loss

Risperidone crude repulp

Reactor R1032

(680 L SSR)

Centrifuge CF1003/

CF1004 (48")

Dryer DR1402

(48 Trays)







Stage IX

Risperidone Crude Repulp

Methylene Chloride

Activated charcoal

Methylene Chloride

Reaction mass

Reaction mass Hazardous Waste

ETP

Methylene Chloride

Reaction mass

Reaction mass Vapour loss

DMF Dist. MDC

Sale

Reaction mass

Reaction mass ML to ETP

DMF

Acetone

Wet cake

Wet cake Vapour loss

Risperidone pure

Sparkler filter

SF1015/ SF1016

(18")

Reactor R1032

(1000 L SSR)

Centrifuge CF1009/

CF1010 (48")

Reactor R1016

(1600 L GLR)

DCRVD1401/

DCRVD1402

(1000 L)







Stage X

Risperidone Pure

Acetonitrile

Reaction mass

Reaction mass ML

Sale

Acetonitrile

Wet cake


Dry Risperidone

Dry Risperidone Handling loss to ETP

Risperidone

Risperidone Handling loss to ETP

Risperidone

Risperidone Handling loss to ETP

Risperidone

Reactor R1032

(1000 L SSR)

Centrifuge CF1009/

CF1010 (48")

DCRVD1401/

DCRVD1402

(1000 L)

Multi Mill MM1402/

MM1401

Jet Mill JM1401

Sifter SR1101/

SR1401







Material Balance:

Stage I

INPUT

OUTPUT


4-(2-4-Difluoro

benzoyl oxime)-

piprodine - rs oxime

pure in chem name

1.43 Product 1.00

Caustic potash flakes 3.29 As Emission 0.79

RS Amine Hexane

15.71 Hazardous Waste

0.00

Water 3.29 Effluent 7.00

Recovered

Solvent

14.92

As moisture 0

Total 23.71

Total 23.71

Stage 2

INPUT OUTPUT


RSPP 2 amino pyridine 0.74 Product 1.00

Aagbl alpha acetyl

gamma butyrolactone


Toluene


0.00

Caustic soda lye 2.61 Effluent 9.76

Methanol

3.20 Recovered

Solvent

4.25

Phosphorous

oxychloride

1.38 As moisture 0

Water 5.00








Stage3

INPUT OUTPUT

Chemical name kg

Name Kg


RS

Chloride Hyflo supercel


Hydrochloric acid cp 0.60 Sludge 0.02

Water 6 Effluent 6.60

By product 0.00

As moisture 0


Stage4

INPUT OUTPUT



Risp. Crude Stage-3 0.77 As Emission 0.00

SODA ASH


0.00


Recovered

Solvent

0.00

As moisture 0


Stage-5

INPUT

OUTPUT



Dimethyl formamide

(DMF)


Risp.

Crude

Repulp

Hazardous Waste

0.00

Effluent 0.00

Recovered

Solvent

3.65

As moisture 0








Stage6

INPUT

OUTPUT

Chemical name kg

Name Kg


Risp.

pure Methylene dichloride


Dimethyl formamide


0.14

Activated carbon

special grade

0.14 Effluent 0.10

Acetone

0.87 Recovered

Solvent

15.90

As moisture 0


Stage7

INPUT

OUTPUT

Chemical name kg

Name Kg


Risperid

one Acetonitrile


Hazardous Waste

0.00

Effluent 0.00

Recovered

Solvent

5.09

As moisture 0








4) DISOPYRAMIDE PHOSPHATE


Step-1: - Disopyramide Base is dissolved in Isopropanol on treatment with mixture of

Ortho Phosphoric acid & Isopropanol yields Disopyramide Phosphate. The isolated

Disopyramide Phosphate is washed with Isopropanol followed by drying.







REACTION:







Stage I Disopyramide Phosphate Product Code- 1300014

ML Vapour Loss

Isopropyl Alcohol

Disopyramid Base

Residue

Activated Charcoal ETP

Dist. IPA

Sale

Reaction Mass

Reaction Mass

Hazardous waste

Isopropyl Alcohol

Reaction mass

Hazardous Waste


Ortho Phosphoric Acid I.P.

Isopropyl Alcohol

Reaction Mass

Reaction Mass

ML

Isopropyl Alcohol

Wet cake

IPA Recovery

Reactor

R1008

(1360 L

GLR)Reactor R1017

(680 L SSR)

Sparkler filter

SF1011/

SF1014

(14"/14")

Reactor R1008

(1360 L GLR)

Centrifuge

CF1009/

CF1010

(48"/48")

FLOW DIAGRAM:








Disopyramide Phosphate (Dried)

Disopyramide Phosphate (Dried) Milling loss to ETP

Disopyramide Phosphate milled

Disopyramide Phosphate milled Sifting Loss to ETP

Disopyramide Phosphate

Sifter SR1101

(30")

Multi Mill

MM1401/

MM1402

DCRVD1402/

DCRVD1401

(1000 L/1000 L)







MATERIAL BALANCE:

INPUT

OUTPUT

Chemical name kg

Name Kg

Disopyramid base(in house) 0.94

Product 1.00

Isopropanol (IPA) 7.97

As Emission 0.40

Ortho phosphoric acid i.p. 0.33

Hazardous

Waste 0.12


grade/charcole 0.12

Effluent 0.27

Recovered

Solvent

7.57

As moisture 0

Total 9.36

Total 9.36







5) DIPHENOXYLATE HCL


Step-1: - Ethanolamide

Diethanolamine is reacted with p-Toluene Sulphonyl Chloride to give Ethanolamide

Preparation.

Step-2: - Nitrileamide, Contract Manufacturing

Ethanolamide is reacted with Thionyl Chloride to give Dichloro compound (Dichloro

compound formation) it is then again reacted with Benzyl Cyanide (Phenyl Acetonitrile) to

give Nitrileamide.

Step-3: - Diphenoxylate HCL Crude

Nitrileamide is reacted with Sulphuric Acid to form TPCP, Which on treatment with

Denatured sprit with 5% Acetone gives TPCP Ester. TPCP Ester is converted to Amino Ester

by treatment with Soda Ash. Amino ester is condensed with 4- Bromo2,2-diphenyl butyro

nitrile in presence of Soda Ash to form Diphenoxylate base. Diphenoxylate base is then

extracted in Methylene Chloride which on reaction with hydrochloric acid to give

Diphenoxylate Hydrochloride Crude. Diphenoxylate Hydrochloride Crude wet is then

isolated & dried to yield Diphenoxylate Hydrochloride Crude.

Step-4: - Ethanolamide

Diphenoxylate Hydrochloride crude is dissolved in DSP acetone, charcoalized, filtered,

crystallized & dried to get Diphenoxylate Hydrochloride.







REACTION:







Stage I Ethanolamide Product Code- 12000301

Reactor R1024

&R1028 Vapour Loss

ML

p-Toluene Sulphonyl Chloride Aq. Layer Aq. Layer

Water

Toluene Residue

Dist. Toluene

Reaction Mass

Total

Reaction Mass Vapour loss

Sodium Bicarbonate

Diethanolamine

Water

Hazardous Waste

Reaction Mass

ML

Water

Wet cake


Ethanolamide

ML Recovery

Reactor R-1021

( 3000 L GLR)

Reactor R-1024

(5000 L SSR)

Centrifuge

CF1007 (48")

Dryer DR1002/

DR1003 (48 Trays)

FLOW DIAGRAM:







Stage III Diphenoxylate Hydrochloride Crude Product Code- 1201048 Product Code No.:- 2800347

Vapour Loss

(Drying of reactor) Acetone

Acetone (For Sale)

Recovered MDC from DPX HCl

Crude

Aqueous Layer

Nitrileamide Vapour Loss Caustic Lye

Water

Sulphuric Acid (98 %) Acidic Dist. DSP Acetone

Sale MDC Layer

Water

Denatured spirit with 5% Acetone Vapour Loss

MDC Layer

Reaction mass

Reaction mass MDC Layer

Acetone (For Sale)

(Drying of reactor) Acetone

Vapour Loss

Water MDC Layer

Lower Boiler

Soda ash

Residue

Caustic Soda Lye

Aq. Layer

Recovered MDC pure from

DPX HCl Crude EP

70% Sulphuric Acid ETP

Methylene Chloride

Reaction mass

Reactor R-1024

(5000 L SSR)

Reactor R-1021

( 3000 L GLR)

Reactor R-1009/

R1021

(3000 L/3000 L

GLR)

Reactor R-1031/

R1028

(1600 L/3000 L

GLR)

Reactor R-1009/

R1021

(3000 L/3000 L

GLR)

Recovery of Recovered MDC From DPX HCl Crude







Product Code No.:- 2800348

Reaction mass

Reactor R-1009/

R1021

(3000 L/3000 L

GLR) Vapour Loss

Recovered MDC from DPX HCl

Crude

Aqueous Layer

Caustic Lye

Reaction Mass Water

Tolenen Layer


Reactor R-1031/

R1028

(1600 L/3000 L

GLR) Vapour Loss

Water Rec. MDC distilled Toluene layer

4 Bromo 2-2 Diphenyl Butyro Nitrile Aqueous Layer

ETP

Sodium Carbonate Solvent distilled

MDC Layer

Methylene Chloride

Reactor R-1009/

R1021

(3000 L/3000 L

GLR) Vapour Loss

Reaction mass Toluene layer

Lower Boiler

Residue

Reaction mass

Recovered Toluene pure

from DPX crude EP

Water

Reaction Mass

Reactor R-1024

(5000 L SSR)

Reactor R-1028

( 3000 L GLR)

Reactor R-1028

( 3000 L GLR)

Recovery of Recovered Toluene From ML of DPX HCl







Reaction Mass

HCL Aq. Layer

ETP

Water

Reaction mass


MDC Distilled

Toluene Aqueous layer

Mixed solvent

Sale

Reaction Mass

Reaction Mass

ML (Toluene)

Water

Water ML

Toluene ETP

Wet Cake

Sod. Carbonate

Water

Reaction Mass

Reaction Mass

Wet Cake Aq. Layer

ETP

Water

Methylene Chloride

Reaction mass

Reaction mass

Aq. Layer

ETP

Water

Reaction Mass

Reactor R-1028

( 3000 L GLR)

Reactor R-1024

( 5000 L SSR)

Reactor R-1021

( 3000 L GLR)

Reactor R-1028

( 3000 L GLR)

Centrifuge

CF1007 (48")

Reactor R-1028

( 3000 L GLR)







Reaction mass

Aq. Layer

HCl ETP

Water

Reaction Mass


Toluene MDC Distilled

Water Mixed solvent

Sale

Reaction Mass

Reaction mass

Water

ML to ETP

Toluene ETP

Wet Cake


DPX HCl Crude

Reactor R-1021

( 3000 L GLR)

Dryer DR1002/

DR1003 (48 Trays)

Reactor R-1028

( 3000 L GLR)

Centrifuge

CF1007 (48")







Stage IV Diphenoxylate Hydrochloride EP Product Code- 1300565

Vapour Loss

Acetone Acetone for sale ML

Lower Boiler

Diphenoxylate Hydrochloride crude Vapour Loss

Residue

DSP with 5% Acetone

Dist. DSP/Acetone (Higher

Boiler

Activated Charcoal

Reaction Mass

Reaction mass Solid Waste

ETP

DSP with 5% Acetone Acetone for sale

Acetone

Reaction Mass


Acetone for sale

Acetone Dist. DSP Acetone

Reaction Mass

Reaction Mass

ML

DSP with 5% Acetone

Acetone for sale

Acetone

Wet cake

Centrifuge CF1006

(36")

Reactor R-1016

( 1650 L GLR)

Reactor R-1009

(3000 L GLR)

Sparkler Filter

SF1002 & SF1015

(18")

Reactor R-1009/

R1016

(3000 L/1600 L

GLR)

ML Recovery







Reaction Mass milling loss

Acetone Acetone for sale

Wet cake


DSP Acetone

Dry DPX HCl

Dry DPX HCl Milling loss

Diphenoxylate Hydrochloride

Dry DPX HCl Sifting loss

Diphenoxylate Hydrochloride

Fritz mill (FM1403)

Sifter

SR1101/SR1401

(30")

Fritz mill (FM1401)

DCRVD1403

(1000 L)







MATERIAL BALANCE:

Stage-1

INPUT

OUTPUT

Chemical name kg

Name Kg

Diethanolamine 0.52 Product 1.00

Ethanolamide

Para toluene sulphonyl

chloride


Toluene

0.65 Hazardous

Waste

0.00

Sodium bicarbonate 0.56 Effluent 8.25

Water

6.98 Recovered

Solvent

0.61

As moisture 0


Stage-2 at Third party

Stage 3

INPUT

OUTPUT

Chemical name kg

Name Kg


Bromodiphenyl

butyronitrile


Sulphuric acid cp 98% 1.37

70 % sulphuric acid CP 0.27

Absolute alcohol with

5% acetone

5.11

DPX Crude Soda ash 2.26

Methylene chloride 28.76

Toluene 14.36


Hydrchloric acid cp 0.89

Acetone 1.11

Water

5.96 Hazardous

Waste

0.00

Effluent 13.60

Recovered

Solvent

46.86

As moisture 0








Stage 4

INPUT

OUTPUT

Chemical

name kg

Name Kg


DPX Final

Denatured

absolute

alcohol


Activated

carbon

special

grade


0.17

Acetone 1.40 effluent 1.56

Recovered Solvent

3.98

As moisture 0








6) AZATHIOPRINE


Step-1: - Dimethyl Oxamide

Diethyl Oxalate (DEO) is reacted with Mono Methyl Amine (MMA) to give Dimethyl

Oxamide (Amide formation).

Step-2: - Chloromethylimidazole crude (CMI Crude), Contract Mfg.

Dimethyl Oxamide (DMO) is cyclized and chlorinated with Phosphorus Pentachloride to give

Chloromethylimidazole (Crude)

Step-3: - Chloromethylimidazole Distilled (CMI Distilled), Contract Mfg.

Chloromethylimidazole (Distilled) is produced by vacuum distillation of

Chloromethylimidazole (Crude)

Step-4: - Chloromethylimidazole Nitrate (CMI Nitrate), Contract Mfg.

Chloromethyl imidazole (Distilled) is nitrated with conc. nitric acid to give

Chloromethylimidazole nitrate (CMI nitrate).

Step-5: - Chloromethyl nitro imidazole (Nitrazole)

CMI Nitrate is treated with conc. sulphuric acid to give Chloromethyl nitro imidazole

(Nitrazole).

Step-6: - 6 - Mercaptopurine

Hypoxanthine is thionated by Phosphorus Pentasulphide to give 6- mercaptopurine.

Step-7: - Azathioprine Crude

6-Mercaptopurine (MP) and Chloromethyl nitro imidazole are reacted to give Azathioprine

(crude) (Dehydrochlorination)

Step-8: - Azathioprine

Azathioprine crude is purified with a mixture of acetone and water and charcoal treatment.







REACTION:







FLOW DIAGRAM:

Stage I

Mono Methylamine Solution

Diethyl Oxalate

Reaction mass

Reaction mass

ML

Hexane

Wet cake

Wet cake

Vapour Loss

Domethyl Oxamide

Reactor SSR-

1002

Centrifuge

CF - 1008

Dryer DR 1001 /

DR 1401







Stage IV

ML

Methylene dichloride Sodium Bicarbonate

CMI distilled Water Aq. Layer

Nitric Acid Sodium Sulfate

Reaction Mass

Reaction Mass

Reaction mass

Solid waste

Reaction Mass Methylene Chloride

ML Reaction mass

Wet cake

vapour Loss

Reaction mass

Dist. MDC

Wet Cake

ML Residue

Wet cake


CMI Nitrate

ReactorReactor

GLR-1014

Vacuum Filter

Vacuum Filter

VF-1001

Reactor

Centrifuge

CF 1008

Dryer

DR 1001







Stage V

Sulphuric acid LR

CMI Nitrate

Reaction Mass

Reaction mass

Water

Reaction Mass

Reaction Mass

Effluent to ETP (Acidic)

Water

Wet cake


Nitrazole

Reactor

GLR-1013

Reactor

GLR 1010

Centrifuge

SS CF-1008

Dryer

DR 1001







Stage VI

Caustic Lye 45%

Water

H2S Gas

Hazardous Waste (NaHS

Scrubber soln.)

Pyridine H2S Gas

Hypoxanthine

Phosphorous Pentasulfide

Purified Water

HCL

Liq. Ammonia

Reaction Mass

Reaction Mass

Hazardous Waste (6-Mercapto

ML) pH 3.8 to 4.2.

Wet cake

Purified Water

Purified Water

Sodium Carbonate

Purified Water

Effluent to ETP (pH 5 to 6)

Wet Cake Effluent to ETP (pH 8 to 9)

Effluent to ETP (pH 7 to 8)

Wet cake of 6-Mercaptopurine

H2S Gas

Scrubber

Reactor -

GLR 2104

Centrifuge

CF 2102

Reactor -

GLR 2104

Centrifuge

CF 2102







Stage VII

Purified Water

Sodium Carbonate Anhydrous

6-Mercaptopurine

Nitrazole

Reaction Mass

Total

Reaction Mass

Activated Charcoal Hazardous Waste

Purified Water Filtrate as reaction mass

Total

HCL

Filtrate as reaction mass

Purified Water

Reaction Mass

Total

Reaction Mass Effluent to ETP (pH 3.8 to 4.2)

Purified Water Effluent to ETP (pH 5 to 5.5)

Wet cake of Azathioprine Crude

Total

Wet cake of Azathioprine Crude

Acetone

Purified Water

Reaction Mass

Total

Reaction Mass

Acetone Effluent to ETP

Purified WaterWet cake of Azathioprine

Crude

Total

Reactor -

SSR 2102

Sparkler Filter

SF 2101/2102 &

Candle Filter

CAF 2101

Reactor -

GLR 2103 /

GLR 2105

Centrifuge

CF 2102

Reactor -

GLR 2103 /

GLR 2105

Centrifuge

CF 2102







Stage VIII

Azathioprine Crude Lot - I +II

Acetone

Purified Water

Reaction Mass

Reaction Mass

Activated Charcoal Hazardous Waste

Purified Water Filtrate as reaction mass

Acetone Recovered Acetone

Filtrate as reaction mass

Purified Water

Reaction Mass

Reaction Mass

Purified Water Effluent to ETP

Acetone Effluent to ETP (pH 5 to 5.5)

Purified Water Wet cake of Azathioprine Pure

Wet cake of Azathioprine Pure

Effluent to ETP

Dry Azathioprine

Dry Azathioprine

Handling loss to ETP

Azathioprine Pure

Dry Azathioprine


Azathioprine Pure

Dry Azathioprine


Azathioprine Pure

Jet Mill JM2101

Sifter SR2101

Reactor -

SSR 2102

Sparkler Filter

SF 2103/2104 &

Candle Filter

CAF 2101

Reactor -

GLR 2103 /

GLR 2105

Centrifuge

CF 2102

Drier DCRVD

2101

Multi Mill MM

2101







MATERIAL BALANCE:

INPUT

OUTPUT

Chemical name kg

Name Kg

Diethyloxylate 1.38 Product 1.00

Mono methylamine solution 1.68 As Emission 0.01

DMO

Hexane 0.28 Hazardous

Waste

0.00

Effluent 2.06

Recovered

Solvent

0.27

As moisture 0


CMI

Crude.

CMIDist.

Stage2 & 3 At Third Party.

Stage 4

INPUT

OUTPUT

Chemical name kg

Name Kg

CMI

nitrate


Methylene chloride (non ex) 2.31 As Emission 0.12

Nitric acid lr grade 0.53 Hazardous

Waste

0.00

Effluent 0.23

Recovered

Solvent

2.20

As moisture 0








Stage 5

INPUT OUTPUT



Nitrazole Sulphuric acid L.R. 3.54 As Emission 0.00

Nitric acid LR grade 6.41 Hazardous

Waste

0.00


Recovered

Solvent

0.00

As moisture 0


Stage6

INPUT

OUTPUT

Chemical name kg

Name Kg

Hypoxanthine 0.88 Product 1.00

6

Mercatopurin

e

Pyridine 3.46 As Emission 0.21

Phosphorous

pentsulphide

0.88 Hazardous

Waste

0.00

Hydrochloric acid cp

(non ex)

4.25 Effluent 28.53

Liquor ammonia lr (non

ex)

0.55

Chloroform (non ex) 0.66


Sodium carbonate 0.06

Water 20.94

Recovered

Solvent

3.91

As moisture 0








Stage 7

INPUT

OUTPUT

Chemical name kg

Name Kg


Stage-5 0.54 As Emission 0.00

Aza

Crude

Soda ash 0.86 Hazardous

Waste

0.11

Hydrochloric acid (non

ex)

1.54 Effluent 39.04

Activated

carbon/charcoal (non ex)

0.11 Recovered

Solvent

0.00



Stage 8

INPUT

OUTPUT

Chemical name kg

Name Kg


Aza Acetone (non ex) 46.34 As Emission 2.32


grade

0.12 Hazardous

Waste

0.12


Recovered

Solvent

44.02

As moisture 0








7) MYCOPHENOLATE MOFETIL


Step-1: - Mycophenolate Mofetil Crude

The reaction of Mycophenolic Acid with 4-(2-Hydroxyethyl) Morpholine (HEM/ Ethanol

Morpholine) in Toluene followed by Methanol gives Mycophenolate Mofetil (crude).

(Esterification).

Stage-2: - Mycophenolate Mofetil

Mycophenolate Mofetil crude is purified in Acetone to give pure Mycophenolate Mofetil.

REACTION:







Stage I Mycophnolate Mofetile Crude

Toluene Marph. Ethanol+Toluene Mix.

Marpholine Ethanol

Toluene for flushout Aqueous Layer

Toluene

Mycophenolic Acid Aqueous Layer

Purified water

Sodium Bicarbonate wash

Reaction Mass

Sodium Bi carbonate unloading

Reaction MassSodium Bi carbonate unloading

Purified water

Sodium Bicarbonate

Reaction Mass

Reaction Mass

ML

Wet material

Wet material

Loss in Drying

Mofetile crude

Reactor R2104

(3000 L) GLR

Reactor

R2103/2105

(5000 L) GLR

Centrifuge

CF2101/2102 (48")

DCRVD 2101

(700 L)

FLOW DIAGRAM:







Stage II Mycophnolate Mofetile

Acetone

Mofetile crude

Reaction mass

Reaction Mass

Acetone Wash

Reaction mass

Reaction mass

Recovery Acetone

Acetone

Vapoure loss

Residuel volume

Residuel volume ML For Cell

Wet cake


Dry Material

Dry Material Loss in Milling

Mill Material

Mill Material

Loss in sifting

Final Product

Sifter SR2101 (30")

Reactor

R2103/2105

(5000L GLR)

Sparkler filter

SF2104 (14")

Reactor R-

2104/2103

(3000/5000 L GLR)

Centrifuge CF-2101

(48")

DCRVD 2101

(700 L)

Multi mill

MM 2101 (8")







MATERIAL BALANCE:

Stage I

INPUT

OUTPUT

Chemical name kg

Name Kg

Mycophenolic Acid 1.04 Product 1.00

MICOMOFETIL

CRUDE

Toluene (drums) 7.27 As Emission 0.53

4-(2-hydroxyethyl)

Morpholine

0.45 Hazardous

Waste

Sodium bi carbonate 1.25 Effluent 39.55

Sodium di thionite 0.31 Recovered

Solvent

10.03

Methanol (drums) 3.30 As moisture

Water 37.50


Stage 2

INPUT

OUTPUT

Chemical name kg

Name Kg

MYCOPHENOLATE

MOFETIL Stage I 1.1

Product 1.00


Hazardous

Waste

Effluent

Recovered

Solvent

9.57

As moisture








8) MYCOPHENOLATE SODIUM


Step-1: - Mycophenolic Acid reacts with caustic soda flakes to form Mycophenolate

Sodium Crude.

Step-2: - Mycophenolate Sodium Crude is repulped with Denatured absolute alcohol to get

Mycophenolate Sodium.

REACTION:







FLOW DIAGRAM:

Stage I Mycophenolate Sodium Crude Product Code-

Denatured Absolute Alcohol

Sodium Hydroxide Flakes

MycophenolicAcid

Denatured Absolute Alcohol for CF wash

Reaction mass

Reaction mass

ML

Wet cake

Wet Cake

Vapour loss

Dry material

Dry Material Lossin Milling

Myco. Sodium Crude

Reactor R2104

(3000 L GLR)

Centrifuge

CF2102 (48")

DCRVD2101

(1000 L)

Multi mill

MM2101







Stage II Mycophenolate Sodium Product Code-

Denatured Absolute Alcohol

Myco. Sodium Crude

Denatured Absolute Alcohol for CF wash

Reaction mass

Reaction mass

ML

Wet cake

Wet Cake

Vapour loss

Dry material

Dry Material Lossin Milling

Mill Material

Reactor R2104

(3000 L GLR)

Centrifuge

CF2102 (48")

DCRVD2101

(1000 L)

Multi mill

MM2101







MATERIAL BALANCE:

Stage I

INPUT

OUTPUT

Chemical name kg

Name Kg

Mycophenolic acid 1.05 Product 1.00

Mycomofetil

sodium

Caustic soda pallets 0.16 As Emission 1.47

Denatured absolute

alcohol

(5% acetone)

29.47 Hazardous

Waste

Effluent

Recovered

Solvent

28.21

As moisture

Total 30.68

Total 30.68







9) PROPANTHELINE BROMIDE


Step:1: - Condensation of Di isopropyl Amino Ethyl Chloride Hydrochloride with

Xanthanoic acid to give Propantheline Base which on treatment with Methyl Bromide gives

Propantheline Bromide Crude. It is then further treated with activated charcoal and

filtered. Then it is isolated by Methyl Ethyl Ketone followed by centrifugation and then

drying to yield Propantheline Bromide.







REACTION:







FLOW DIAGRAM:

Stage II Propantheline Bromide

Chloroform

Vapour Loss (Chloroform + Water)

Xanthanoic Acid

Dist. Chroroform

Soda Ash Sale

Aqueous layer

DIPC Hydrochloride

Water Waste Sodium sulfate Hazardous Waste

Methanol Mathanol for Sale

Sodium Sulphate Anhydrous

Reaction Mass

Hazardous Waste

Reaction mass

Methyl Bromide

Reaction mass

Reaction Mass

Chloroform Vapour Loss

Sodium Sulphate Anhydrous Aq.Layer

ETP

Activated charcoal Waste Sodium sulfate Hazardous Waste

water Hazardous waste (Charcoal)

Reaction mass

Reactor R-

1017

(680 L SSR)

Reactor R-

1017

(680 L SSR)

Reactor R-

1006

(225 L SSR)







Reaction mass

Chloroform

Reaction mass

Reaction mass

Milling loss to ETP

Methyl Ethyl Ketone

Rec. Chloroform

Sale

Mix. Solvent distilled (Chloroform+MEK)

Sale

Reaction Mass

Jet milling loss to ETP

Reaction Mass

Methyl Ethyl Ketone ML

Sale

Wet cake


Dry Propantheline bromide for MEK repulp

Reaction mass

Chloroform

Methyl Ethyl Ketone

Reaction Mass

Reaction Mass

Methyl Ethyl Ketone ML

Sale

Wet cake

Reactor R-

1025 /R1032

(1000 L SSR)

Centrifuge

CF1009/CF1010

(48")

Reactor R-

1025 /R1032

(1000 L SSR)

Centrifuge

CF1009/CF1010

(48")

DCRVD1401/

DCRVD1402

(1000 L)

Sparkler Filter

SF1014/SF1011

(14")








Dry Propantheline bromide

Semi Dried Propantheline Bromide Handling Loss to ETP

Propantheline Bromide

milled material Vapour Loss

Dry Propantheline bromide

Dried Propantheline Bromide Handling Loss

Propantheline Bromide

DCRVD1401/

DCRVD1402

(1000 L)

DCRVD1401/

DCRVD1402

(1000 L)

Multi Mill (MM1401/

MM1402)

Multi Mill (MM1401/

MM1402)







MATERIAL BALANCE:

Stage I

INPUT

OUTPUT

Chemical name kg

Name Kg

Dipc hydrochloride 0.81 Product 1.00

Xanthalene-9-carboxylic acid (IMP) 0.82 As Emission 1.40

Soda ash 0.61

Chloroform 16.68

Sodium sulphate anhydrous

0.47 Hazardous

Waste

0.60

Methyl bromide pure 0.91 Effluent 27.94

Activated carbon special grade

0.13 Recoverd

Solvent

26.69

Methyl ethyl ketone (MEK) 10.98 As moisture 0

Methanol 0.43

Water 25.79








10) QUINFAMIDE


Step-1: - Para Nitro Anisole

Alkaline Para nitro chloro benzene on refluxing with BTEAC gives Para-Nitro Anisole.

Step-2: - 6-Methoxy Quinoline

Para Anisidine & Para Nitro Anisole in Glycerine reacted with Sulphuric Acid (CP grade) to

give 6 – Methoxy Qunoline. Which is extracted in Toluene & washed with water. Followed

by Activated Charcoal treatment.

Step-3: - 6-Methoxy Tetrahydroxy Quinoline

6 – Methoxy Qunoline is hydrogenated in presence of Raney Nickel to yield 6 – Methoxy

Tetrahydroxy Quinoline

Step-4: - Tetroxyquin

6 – Methoxy Tetrahydroxy Quinoline is reacted with Aqueous Hydrogen Bromide to give

Tetroxyquin HBr salt. Tetroxyquin HBr salt solution in caustic soda lye treated with Sodium

Bicarbonate to give Tetroxyquin.

Step-5: - Dichloro Acetyl Tetroxyquin

Tetroxyquin base is condensed with dichloroacetylchloride in presence of Sodium

Bicarbonate to form Dichloro Acetyl Tetroxyquin

Step-6: - Quinfamide Crude

This stage consists of 2 parts 1) 2-furoic acid is treated with Thinyl Chloride to form 2-

Furoyl Chloride 2) Dichloroacetyl Tetroxyquin and 2-Furoyl Chloride are reacted to form

Quinfamide Crude.

Step-7: - Quinfamide

Quinfamide Crude is Purified in Ethyl Acetate and dried to produce Quinfamide







REACTION:







FLOW DIAGRAM:

Stage I - P-Nitroanisole Product Code- 1200357

P-Nitro Chloro benzene

Caustic soda flakes Vapour Loss

Methanol

Dist. Methanol

BTEAC Sale

Reaction Mass

Total

Reaction mass

ML

Methanol Sale

Water

Wet cake for water Repulp

Total

Wet Cake

Water

Reaction mass

Total

Reaction Mass

ML

Hexane ETP

Wet cake

Total

Wet cake

Vapour Loss

P-Nitroanisole

Total

Reactor

R-1026

( 1000 L SSR)

Dryer

(DR1002/ DR1003)

48 Trays

Vacuum filter

(VF1002)

Reactor

R-1026

(1000 L SSR)

Vacuum filter

(VF1002)







Stage IV - Tetraxyquin Product Code- 1200360

6-Methoxy Tetrahydroxy Quinoline Vapour Loss

Hydrobromic Acid aqueous 48% Acidic methanol

ETP

Dist. HBr-Hazardous Waste

Reaction mass

Total

Reaction mass

ML

ETP

Wet cake

Total

Wet cake

Water

Dilute caustic soda lye

Sodium bicarbonate

Reaction mass

Total

Reaction mass

ML

Toluene ETP

Water

Tetraxyquin (wet)

Total

Centrifuge

CF1003/ CF1004

(48')

Reactor

R1029

(2000 L GLR)

Reactor

R1029

(2000 L GLR)

Centrifuge

CF1003/ CF1004

(48')







Stage V - DTHQ Product Code- 1200361

Tetraxyquin Vapour Loss


Sodium Bicarbonate

Dichloro Acetyl Chloride

Reaction mass


Methylene Dichloride Hazardous waste

ETP

Reaction mass

Aq. Layer

Reaction mass ETP


Reaction mass

Reaction mass

HCL Aq. Layer

Methylene Dichloride ETP

Water

Reaction mass

Reactor

R1029

(2000 L GLR)

Reactor

R1002

(1360 L SSR)

Reactor

R1029

(2000 L GLR)

Vacuum Filter

VF1001







Vapour Loss

Reaction Mass Rec. MDC

Aqueous layer

Sod. Bicarbonate Aq. Layer Water ETP

ETP Dist . MDC

Water

Methylene Dichloride Residue

Reaction mass Total

Reaction mass

Water Aq. Layer

ETP

Reaction mass

Reaction Mass

Reaction mass

Reaction mass

Sodum Sulfate Anhydrous Hazardous Waste


Reaction mass


Ethyl Acetate Rec. MDC Treatment

MDC Distilled

Hexane

Reaction mass

Reactor

R1002

(1360 L SSR)

Reactor

R1029

(2000 L GLR)

Reactor

R1029

(2000 L GLR)

Reactor

R1002

(1360 L SSR)

Reactor

R1002

(1360 L SSR)

Reactor

R1029

(2000 L GLR)







Reaction Mass

Ethyl Acetate

ML

Hexane Sale

Wet cake


DTHQ

Dryer

DR1401

(48 Trays)

Centrifuge

CF1001/CF1008

(36/48")







Stage VI - Quinfamide Crude Product Code- 1200363

Methylene Dichloride Vapour loss

2-Furoic Acid

Thionyl Chloride

Reaction mass

DTHQ


Reaction mass

Reaction mass


Reaction mass

Reaction mass

Reaction mass (R1008)

Triethyl Amine Aq. Layer

Water

MDC

Reaction mass

Reaction mass

Sodium Bicarbonate

Aq. Layer

Water

MDC

Reaction mass

Sparkler Filter

SF1003/SF1011

(14"/14")

Reactor

R1030

(3000 L GLR)

Reactor

R1008

(1360 L GLR)

Reactor

R1019

(3000 L SSR)

Reactor

R1019

(4000 L SSR)

MDC Used for Cleaning R1008

send to Sale







Reaction mass Aq. Layer

MDC

Water

Reaction mass

Reaction mass

Reaction mass

Reaction mass Solid waste

Sodium Sulphate

MDC

Reaction mass

Reaction mass

Activated Charcoal

MDC

Reaction mass

Reaction mass

MDC Solid waste

ETP

Reaction mass


Distilled MDC

Reaction mass


Ethyl Acetate Distilled MDC

Reaction mass

Reaction mass ML

Sale

Ethyl acetate

Quinfamide Crude

Centrifuge

CF1003/ CF1004

(48"/48")

Reactor

R1030

(3000 L GLR)

Reactor

R1019

(4000 L SSR)

Reactor

R1030

(3000 L GLR)

Sparkelr Filter

SF1003/SF1011

(14:/14")

Reactor

R1008

(1360 L GLR)

Reactor

R1030

(3000 L GLR)

Reactor

R1019

(4000 L SSR)







Stage VII - Quinfamide Product Code- 1300033

Quinfamide Crude Vapour loss

ML Vapour Loss

Activated Charcoal

Dist . Ethyl acetate

Ethyl Acetate

Reaction mass Residue

Reaction mass Hazardous waste

Ethyl Acetate

Reaction mass


Dist. Ethyl acetate

Reaction mass

Reaction mass

ML

Ethyl Acetate

Wet cake

Reactor

R1030 /R1027

(3000 L GLR)

Reactor

R1030/ R1027

(3000 L GLR)

Reactor

R1019/ R1023

(3000 L SSR)

Sparkelr Filter

SF1012/SF1016

(18/18")

Centrifuge

CF1010/ CF1009/

CF1011

(48")







Wet cake from 1st charcolisation Vapour loss

Activated Charcoal

Ethyl Acetate

Reaction mass

Reaction mass Hazardous Waste

Ethyl Acetate

Reaction mass


Dist. Ethyl acetate

Reaction mass

Reaction mass

ML

Ethyl Acetate

Wet cake

Wet cake

Vapour Loss

Dryed material

Reaction mass milling loss

Milled material

Reaction mass sifting loss

Quinfamide

Reactor

R1030

(3000 L GLR)

Sparkelr Filter

SF1012/SF1016

(18/18")

Reactor

R1019 / R1023

(3000 L SSR)

Sifter

SR1101/ SR1401

(30")

Multi mill

MM1401/MM1403

DCRVD1402/

DCRVD1403

(1000 L/1000 L)

Centrifuge

CF1010/ CF1009/

CF1011

(48")







MATERIAL BALANCE:

Stage I

INPUT

OUTPUT

Chemical name kg

Name Kg

P nitro chloro benzene 1.17 Product 1.00

Methanol 4.02 As Emission 0.21

Paranitro

anisole Caustic soda flakes

0.45 Hazardous

Waste

0.00

Benzyl triethyl ammonium

chloride

0.01 Effluent

8.82

Hexane 0.26 Recovered

Solvent

4.06



6 MQ & 6

MTHQ Stage2 & 3 At Third Party.

Stage 4

INPUT

OUTPUT

Chemical name kg

Name Kg

Tetroxyqui

n Stage 3

0.96 Product

1.00

Hydrobromic acid aqueous

48%

7.64 As Emission

0.01

Caustic soda lye 0.66 Hazardous

Waste

0.00

Sodium bicarbonate 0.06 Effluent 5.56

Toluene

0.11 Recovered

Solvent

7.36









Stage 5

INPUT

OUTPUT

Chemical name kg

Name Kg


DTHQ Dichloroacetyl chloride 0.88 As Emission 0.59

Sodium bicarbonate 1.03 Hazardous

Waste

0.16

MDC 10.01 Effluent 6.33


Solvent

11.17

Hydrochloric acid comm 0.20

Ethyl acetate 0.45

Sodium sulphate anhydrous 0.16



Stage6

INPUT

OUTPUT

Chemical name kg

Name Kg


Quinfamid

e Crude 2-furoic acid


Thionyl chloride

0.58 Hazardous

Waste

0.04

MDC 16.14 Effluent 11.85

Triethylamine 0.39

Sodium bicarbonate 0.58


Caustic lye 3.07

Activated charcoal 0.04

Ethyl acetate

1.19 Recovered

Solvent

17.13

Methanol 0.31 As moisture 0

Water 7.25








Stage7

INPUT

OUTPUT

Chemical name kg

Name Kg



Quinfamid

e


grade

0.12 Hazardous

Waste

0.12

Effluent 0.15

Recovered

Solvent

29.73

As moisture 0








11) CLOPIDOGREL BISULFATE


Step-1: - Clopidogrel CSA Salt

Step-1: - Clopidogrel Freebase (crude)

i. This step involves the cyclisation of couple ester (reactant) to Clopidogrel molecule (product)

using Para-formaldehyde as reagent.

ii. Clopidogrel Freebase (crude) is liquid in nature.

Step-2: - Clopidogrel CSA salt

i. It is just a chiral purification of Clopidogrel free base using chiral reagent L (-)-Camphor

Sulphonic acid.

ii. This material is salt and solid in nature.

Step-2: - Clopidogrel Bisulphate

Step-1: - Clopidogrel Freebase (Pure)

i. This step involves the isolation of Clopidogrel freebase in its pure form from its Clopidogrel CSA

salt using ammonia.

ii. Clopidogrel Freebase (pure) is liquid in nature.

Step-2: - Clopidogrel Bisulfate

i. This step involves the preparation of final product Clopidogrel BS using Concentrated Sulphuric

acid.

ii. This material is again a salt and solid in nature.







REACTION:







Stage I Clopi. Bisulfate Crude Product Code- 1201019

Water

Chlorophenyl)-N-[2-(2-Thienyl)

Ethyl] Glycine methyl ester

Hydrochloride. [(+)-Couple Ester]

Aq. Layer

Paraformaldehyde ETP

Conc. HCl (CP grade)

Hexane

Aq. Ammonia

Reaction mass


Water

Sodium Bicarbonate Aqueous Layer

ETP

Sodium Sulphate Anhydrous Hazardous Waste

Hexane

Reaction Mass


Acetone Dist.Hexane

Sale

Sulphuric acid

Clopidogrel bisulphate (Seeding)

Reaction Mass

Reaction mass Fil. ML contains batch

Acetone

Reaction Mass

Reactor R-

1017

(680 L SSR)

Reactor R-

1016

(1600 L GLR)

Reactor R-

1032

(1000 L SSR)

Vacuum Filter

(VF1002)

FLOW DIAGRAM:







Fil. ML contains batch

Acetone

Activated Charcoal

Reaction Mass

Reaction Mass

Hazardous waste

Acetone

Reaction Mass

Reaction mass

Sulphuric acid


Reaction Mass

Reaction Mass

ML

Acetone Sale

Clopi. Bisulfate Crude

Reactor R-

1016

(1600 L GLR)

Sparkelr Filter

SF1014/

SF1011 (14")

Reactor R-

1032

(1000 L SSR)

Centrifuge

CF1009/

CF1010 (48")







Stage II Clopi. Bisulfate (Form- II) Product Code- 1300552

Clopi. Bisulfate Crude Dist. Methanol

Sale

Methanol mix Solvent

Sale

Acetone Methanol for sale (Used for cleaning)

Sale

Reaction mass

Reaction mass

Acetone ML

Sale

Wet Cake


Dry material

Dry material Milling Loss to ETP

Milled material

Milled material Sifting Mass to ETP

Clopi. Bisulfate

Reactor R-

1032

(1000 L SSR)

Centrifuge

CF1009/

CF1010 (48")

DCRVD1402/

DCRVD1401

(1000 L)

Multi Mill

MM1401/

MM1402

Sifter SR1101/

SR1401 (30")







MATERIAL BALANCE:

Stage I

INPUT

OUTPUT

Chemical name kg

Name Kg

(+)-Methyl-alpha-(2-

thienylethamino)(2-c

1.00 Product 1.00

CLOPIDOGR

EL CSA SALT

Para formaldehyde 96% 0.13 As Emission 0.75

L(-) camphor sulphonic acid

(IMP)

0.53 Hazardous

Waste

0.04

Hydrochloric acid CP 0.12 Effluent 24.10


Solvent

14.23

Methylene chloride 3.30 As moisture

Acetone 7.91

Liquor ammonia LR 0.43



Water 22.86

Total 40.12

Total 40.12

Stage 2

INPUT

OUTPUT

Chemical name kg

Name Kg

CLOPIDOGREL

BIOSULPHATE

Stage I 1.71 Product 1.00

Hexane 9.48 As Emission 1.17

Liquor ammonia lr 0.37 Hazardous

Waste

0.10

Activated charcoal special

grade

0.10 Effluent 12.98

Ethyl acetate 13.99 Recovered

Solvent

22.30

Sulphuric acid ar grade 0.52 As moisture


Water 11.29

Total 37.55

Total 37.55







12) CLOPIDOGREL BESYLATE


Step-1: - Preparation of Clopidogrel free base (Intermediate I) (III) involves cyclization of

(+)-2-[2-Chlorophenyl]-N-2-(2-thienyl) glycine methyl ester hydrochloride (I).[S-(+)-

couple ester hydrochloride] by introduction of one carbon atom using para

formaldehyde(II) Here water is used as a solvent. Clopidogrel Base (III) obtained is

converted in to its Besylate salt (V) by reacting with benzene Sulphonic acid (IV) in ethyl

acetate.

REACTION:







Stage I Clopi. Besylate Product Code- 1300458

Water

Chlorophenyl)-N-[2-(2-Thienyl) Ethyl]

Glycine methyl ester Hydrochloride.

[(+)-Couple Ester]

Aq. Layer

Paraformaldehyde ETP

Conc. HCl (CP grade) Hazardous Waste

Hexane

Aq. Ammonia

Acetic Acid

Sodium Bicarbonate


Reaction Mass

Reaction mass

Reaction Mass


Activated Charcoal

Hexane


Reaction Mass


Hexane Hazardous waste

Reaction Mass

Reactor R-

1016

(1600 L GLR)

Reactor R-

1017

(680 L SSR)

Reactor R-

1016

(1600 L GLR)

Sparkler filter

SF1011/

SF1014 (14″)

FLOW DIAGRAM:








Ethyl Acetate Milling loss to ETP

Benzene Sulfonic Acid

Clopidogrel Besylate (Seeding)

Reaction Mass

Reaction Mass

Ethyl Acetate

Wet cake keep aside.

Benzene Sulfonic Acid

Ethyl Acetate

Reaction Mass

Benzene Sulfonic acid sol.


Reaction Mass

ML (Contains Batch material proceed

further for operation in R1032)

ML (Contains Batch material proceed

further for operation in R1032)

Reactor R-

1017

(680 L GLR)

Vacuum filter

VF1002

Reactor R-

1032

(1000 L SSR)

Reactor R-

1017

(680 L GLR)







Reaction Mass

ML

Ethyl Acetate Sale

Wet cake


Dry material

Dry material Milling Loss to ETP

Milled material

Milled material Sifting Mass to ETP

Clopi. Besylate

Centrifuge

CF1009/

CF1010 (48")

Sifter SR1101/

SR1401 (30")

DCRVD1402/

DCRVD1401

(1000 L)

Multi Mill

MM1401/

MM1402







MATERIAL BALANCE:

INPUT

OUTPUT

Chemical name kg

Name Kg

(+)-Methyl-alpha-(2-thienylethamino)(2-c 1.33 Product 1.00

Para formaldehyde 96% 0.18 As Emission 0.80

Activated carbon special grade/charcole

0.03 Hazardous

Waste

0.16

Ethyl acetate 4.70 Effluent 36.16

Hydrochloric acid CP

0.08 Recovered

Solvent

15.12

Hexane 10.69 As moisture 0

Acetone 0.53

Liquor ammonia lr 0.43



Acetic acid glacial 0.50

Benzene sulphonic acid 0.51

MDC

2.94

Water

31.11








13) TICLOPIDINE HCL


Stage -1: - Synthesis of Couple amine Hydrochloride

Step - 1A: - Preparation of Tosylate of Thiophene-2- Ethanol

Thiophene-2-ethanol is converted into its tosylate by treatment with p-toluene sulphonyl

chloride in the presence of triethylamine.

Step - 1B:- Preparation of Couple amine Hydrochloride

The in situ tosylate is coupled with 2-chlorobenzylamine in presence of dilute hydrochloric

acid to form couple amine base [N- (2-chlorobenzyl)-2-(2-thienyl) ethylamine], which is

then converted to its hydrochloride, i.e. couple amine hydrochloride.

Stage-2: - Synthesis of Ticlopidine Hydrochloride (Crude)

Couple amine hydrochloride upon treatment with paraformaldehyde in tertiary butanol in

presence of hydrochloric acid forms ticlopidine hydrochloride.

Stage-3:- Purification of Ticlopidine Hydrochloride

The crude product obtained in Step 2 is recrystallized from methanol to give Ticlopidine

Hydrochloride as pure product.







REACTION:







FLOW DIAGRAM:

Stage I Couple amine HCL

OCBA Salt

Aq. Layer

Toluene Water

P-Toluene Sulphonyl Chloride Aq. Layer Caustic Lye

Toluene

Reaction Mass

Reaction Mass

Reaction Mass

Vapour Loss

Toluene Reaction Mass

Aq. Layer Dist . Toluene

Thiophene-2-Ethanol

Rec. OCBA

Water

BTEAC

Caustic lye

Hydrochloric Acid

OCBA

TEA

TBAB

Reaction mass

ReactorReactor

Reactor

Reactor







Reaction mass

Toluene OCBA Salt

Reaction Mass(ML)

Reaction Mass(ML)

HCL + Water (1:1)

Reaction mass

Reaction mass ML Aq. Layer

ML

Toluene Water Vapour loss

Caustic lye Residue

Wet cake

Dist. Toluene


Wet cake

Centrifuge

Reactor

Dryer

Centrifuge

Reactor







Stage II Ticlo crude

Tertiary Butanol

Cleaning Tertiary

Butanol

Coupleamine Hydrochloride

Vapour Loss

Para Formaldehyde


Reaction Mass

Reaction Mass

ML

Ticlo crude

Reactor

Vacuum filter







Stage III Ticlopidine hydrochloride

ML

Methanol

Vapour Loss Vapour loss

Ticlopidine Hydrochloride Crude

Residue

Activated Charcoal

Dist. Methanol

Reaction Mass

Reaction Mass

Solid Waste

Reaction mass


Dist.Methanol

Reaction Mass

Reaction Mass

ML

Methanol

Wet cake


Dry Ticlopidine

Dry Ticlopidine Handling Loss

Ticlopidine

Centrifuge

Dryer

CAD mill

Reactor

Reactor

Sparkler filter

Reactor







MATERIAL BALANCE:

Stage I

INPUT

OUTPUT

Chemical name kg

Name Kg

Thiophene - 2 - ethanol

(IMP)

0.50 Product

1.00

Para toluene sulphonyl

chloride

0.88 As Emission

0.23

Triethylamine 0.04

COUPLEAMI

NE HCL Toluene

4.54

Ortho chloro benzyl amine

(IMP)

1.16

Bteac 0.03

Tetra butyl ammonium

bromide

0.03 Hazardous

Waste

0.00

Hydrochloric acid CP 0.61 Effluent 10.01

Caustic soda lye. 1.52 Recovered

Solvent

4.31



Stage 2

INPUT

OUTPUT

Chemical name kg

Name Kg


TICLOPIDINE

HCL CRUDE Tertiary butanol

2.93 As Emission

0.15

Hydrochloric acid CP 0.01 Hazardous

Waste

0.00

Para formaldehyde 96% 0.41 effluent 0.58

Recovered

Solvent

2.78

As moisture 0








Stage 3

INPUT OUTPUT




TICLOPIDINE

HCL B.P.


grade/charcole

0.08 Hazardous

Waste

0.08

Effluent

Recovered

Solvent

6.05

As moisture 0








14) LAMOTRIGINE


Step-1: - 2-(2, 3-Dichlorophenyl)-(Guanidinoimino) Acetonitrile is refluxed in methanol followed

by charcoalisation and concentration followed by product isolation and then drying gives

Lamotrigine

REACTION:







Stage I Lamotrigine Product Code- 1300022

ML Vapour Loss

2-(2, 3-Dichlorophenyl)-

(Guanidinoimino) Acetonitrile (Schiff's

Base)

Vapour Loss

Methanol

Residue

Activated Charcoal

Rec. Methanol

Reaction Mass

Reaction Mass

Hazardous Waste

Methanol

Reaction mass


Rec. Methanol

Reaction Mass

Reaction Mass

ML

Methanol

Wet cake

ML Recovery

Sparkler filter

SF1012/SF1002

(18"/18")

Reactor

R1030/R1027/

R1028

(3000 L GLR)

Centrifuge

CF1009/CF1010/

CF1011

(48"/48"/48")

Reactor

R1019/R1023

/ R1024

(3000/5000 L

SSR)

Reactor

R1019/R1023/

R1024

(3000 L SSR)

FLOW DIAGRAM:








Dry lamotrigine

Dry Lamotrigine Milling loss to ETP

Lamotrigine

Milled lamotrigine Jet milling loss to ETP

Dry lamotrigine

Jet milled Lamotrigine Sifting loss to ETP

Lamotrigine

Jet mill JM1401

Sifter

SR1101/SR1401

DCRVD1402/

DCRVD1401

(1000 L/ 1000 L)

Multi mill

MM1401/

MM1402







MATERIAL BALANCE:

Stage I

INPUT

OUTPUT

Chemical name kg

Name Kg

Schiff Base 1.14 Product 1.00


Activated charcoal 0.17

Hazardous

Waste

0.31

Effluent

Recovered

Solvent

40.03

As moisture 0








15) PANTOPRAZOLE SODIUM


Stage-1:- Pantoprazole Sodium Crude

Alkaline solution of 5-Difluromethoxy -2-mercapto-1H-Benzimidazole on reaction with 2-

chloromethyl 3,4-dimethoxy pyridine hydrochloride in presence of Di-isopropyl ether yields

Pantoprazole Thioether.

Pantoprazole Thioether is dissolved in MDC. Then the reaction mass is treated with Tertiary

Butyl Ammonium Bromide and Caustic Hypochlorite solution. Ammonium sulfate is added in

reaction mixture to extract the Pantoprazole free base from the MDC layer. Pantoprazole

free base is reacted with Caustic solution to precipitate the Pantoprazole Sodium. Further

this solution is washed with Methanol.

Sodium sulphate treatment is given to reaction mixture then distillation of MDC and MDC

stripping and crystallisation material with wash with acetone.

Stage-2: - Patoprazole Sodium

Purification by Charcoalisation of Pantoprazole Sodium Crude in acetone to yield

Pantoprazole Sodium.







REACTION:







Stage I Pantoprazole Sodium Crude Product Code- 1200322

2-ChloroMethyl-3, 4-Dimethoxy Pyri Dist. MDC Vapour Loss

Water Water Aq. Layer

Caustic Soda flakes Residue

Dist. MDC

Reaction Mass

Reaction Mass

Methylene Chloride

Caustic Soda flakes Hazardous Waste

5-DifluroMethoxy-2-Mercapto-1H-Ben

(PZL Thiol)

Reaction Mass

Reaction Mass

Sodium Hypochlorite

Water

Caustic Soda flakes

Reaction Mass

Treatment of Recovered MDC

Reactor R1003/

R1024

(1500/ 5000 L

SSR)

Reactor R-1007/

R1003

(3600 L SSR)

Reactor R1007/

R1023

(3600/3000 L

SSR)

Reactor

R1003/R1024

(1500/5000 L

SSR)

FLOW DIAGRAM:







Reaction Mass

Tetra butyl Ammonium Bromide Aq. Layer

ETP

Sodium Thiosulphate

Ammonim Sulphate

Reaction Mass

Reaction mass

Caustic soda flakes Milling loss to ETP

Water

Methanol

Reaction mass

Reaction mass


Hazardous Waste

MDC

Reaction Mass

Reaction mass Vapoue loss

MDC Dist. MDC

Acetone

Reaction mass

Reaction Mass

ML

Acetone Sale

Pantoprazole Sodium Crude

Reactor R1007/

R1023

(3600/3000 L

SSR)

Reactor

R1003/R1023

(1500 L SSR)

Reactor R1007/

R1023

(3600/3000 L

SSR)

Reactor R1003/

R1024/R1025

(1500/ 1000 L

SSR)

Centrifuge

CF-1003/

CF1004/CF1007

(48")







Stage II Pantoprazole Sodium ML Recovery

Batch sparklered in 2 lots

ML Vapour Loss

Acetone Vapour Loss

Pantoprazole Sodium Crude wet. Residue

Hyflo supercel

Dist. Acetone

Reaction Mass

Reaction Mass

Hazardous Waste

Actone

Reaction mass


Reaction Mass

Reaction Mass

ML

Acetone

Wet cake


Dry Pantoprazole Sodium

Product Code- 1200899

Reactor R-1007/

R1005

(3600/3000 L SSR)Reactor R-1007

/R1005

(3600 L SSR)

Sparkler filter

SF1013/SF1018

(14")

Reactor R-1003/

R1025

(1500/1000 L

SSR)

Centrifuge

CF-1010/ CF1009

(48")

DCRVD1401/

DCRVD1402

(1000 L)







MATERIAL BALANCE:

Stage I

INPUT OUTPUT


5-difluro methoxy-2-mercapto-

1h-ben (local)

0.46 Product 1.00

panta.

Crude

2-chloromethyl-3,4-dimethoxy

pyri (local)


Tetra butyl ammonium bromide 0.00

Sodium hypochlorite 2.35

Methylene dichloride 11.97

Sodium thiosulphate 0.07


Acetone 1.41

Methanol 0.41 Hazardous

Waste

0.00

Caustic soda flakes 0.42 Effluent 26.54

Ammonium sulphate 1.17 Recoverd

Solvent

13.10



Stage 2

INPUT OUTPUT



panta

Sodium


Hyflo super cel 0.03 Hazardous

Waste

0.03

Effluent 0.42

Recovered

Solvent

3.76

As moisture 0








16) PANTOPRAZOLE SODIUM SEQUEHYDRATE


Stage-1:- Pantoprazole Sodium Crude

Alkaline solution of 5-Difluromethoxy -2-mercapto-1H-Benzimidazole on reaction with 2-

chloromethyl 3,4-dimethoxy pyridine hydrochloride in presence of Di-isopropyl ether yields

Pantoprazole Thioether.

Pantoprazole Thioether is dissolved in MDC. Then the reaction mass is treated with Tertiary

Butyl Ammonium Bromide and Caustic Hypochlorite solution. Ammonium sulfate is added in

reaction mixture to extract the Pantoprazole free base from the MDC layer. Pantoprazole

free base is reacted with Caustic solution to precipitate the Pantoprazole Sodium. Further

this solution is washed with Methanol.

Sodium sulphate treatment is given to reaction mixture then distillation of MDC and MDC

stripping and crystallisation material with wash with acetone.

Stage-2: - Patoprazole Sodium

Purification by Charcoalisation of Pantoprazole Sodium Crude in acetone to yield

Pantoprazole Sodium.

Stage-3: - Pantoprazole Sodium Sequehydrate

Pantoprazole Sodium dissolves in Denatured absolute alcohol (5% DSP acetone). Isopropyl

ether added in two lots to form precipitate. The precipitate then maintained at 8-10°C and

filtered through centrifuge. Wet cake dried in DCRVD to obtain Pantoprazole Sodium

Sesquihydrate

REACTION:







FLOW DIAGRAM:







MATERIAL BALANCE:

Product Pantaprazole Sodium

Stage I

INPUT

OUTPUT

Chemical name kg

Name Kg

5-difluro methoxy-2-

mercapto-1h-ben (local)

0.46 Product 1.00

panta.

Crude

2-chloromethyl-3,4-

dimethoxy pyri (local)


Tetra butyl ammonium

bromide

0.00





Acetone 1.41

Methanol

0.41 Hazardous

Waste

0.00

Caustic soda flakes 0.42 Effluent 26.54

Ammonium sulphate

1.17 Recovered

Solvent

13.10



Stage 2

INPUT

OUTPUT

Chemical name kg

Name Kg


panta

Sodium Acetone


Hyflo super cel

0.03 Hazardous

Waste

0.03

effluent 0.42

Recovered

Solvent

3.76

As moisture 0








Product Pantaprazole Sesqui

Stage I

INPUT

OUTPUT

Chemical name kg

Name Kg

5-difluro methoxy-2-mercapto-

1h-ben (local)

0.46 Product 1.00

panta.

Crude

2-chloromethyl-3,4-dimethoxy

pyri (local)

0.47 As

Emission

0.69

Tetra butyl ammonium bromide 0.00





Acetone 1.41

Methanol

0.41 Hazardous

Waste

0.00

Caustic soda flakes 0.42 effluent 26.54

Ammonium sulphate

1.17 Recovered

Solvent

13.10

Water 22.17 As

moisture

0


Stage 2

INPUT

OUTPUT

Chemical name kg

Name Kg


panta

Sodiu

m Acetone

8.23 As

Emission

0.41

Hyflo super cel

0.03 Hazardous

Waste

0.03

effluent 0.42

Recovered

Solvent

7.82

As

moisture

0








Stage 3

INPUT

OUTPUT

Chemical name kg

Name Kg

panta

Sesqui Stage-2

1.18 Product 1.00

Denatured absolute alcohol (5%

acetone)


Re-covered isopropyl ether

13.14 Hazardous

Waste

0.00

Methanol 0.12 effluent 0.42

Water

0.24 Recovered

Solvent

13.49

As moisture 0

Total 15.61

Total 15.61







17) SERTRALINE HCL


Step-1: - Synthesizing MINE from TETRALONE by reacting with methylamine in presence

of acetone.

Step-2: - The MINE is then reduced in presence of palladium/ charcoal catalyst and then

converted to SINE HYDROCHLORIDE.

Step-3: - The SINE HYDROCHLORIDE is purified in methanol/ charcoal to get CIS-SINE

HYDROCHLORIDE or SINE-C-HYDROCHLORIDE.

Step-4: - The SINE C HYDROCHLORIDE is liberated into SINE C Free base, which is

resolved by treating with mandelic acid, resulting in the formation of SINE CIS MANDELATE

(salt).

Step-5: - Finally SINE CIS MANDELATE is treated with hydrochloric acid to form

SERTRALINE HYDROCHLORIDE (Polymorph I).







REACTIONS:







Stage Sertraline HCl Product Code- 1300385

Sertraline Mandelate

Aqueous Layer

Water ETP

Caustic Soda Palletes

Ethyl Acetate

Reaction Mass

Aqueous Layer Aqueous Layer

ETP

Ethyl Acetate

Hazardous Waste

Reaction mass Aqueous Layer

ETP

Water

Reaction Mass

Reaction Mass

Hazardous Waste

Ethyl Acetate

Reaction mass

Reactor

R-1023

(3000 L SSR)

Sparkler filter

SF1012/ SF1002

(18"/18")

Reactor

R-1027

(3000 L GLR)

Reactor

R-1023

(3000 L SSR)

FLOW DIAGRAM:








IPA HCl Sol.

Seeding of Sert. HCL

Reaction Mass

Reaction Mass

ML to ETP

Ethyl Acetate

Wet cake


Dry Sertraline HCl

Dry Sertraline HCl Milling loss

Sertraline HCl

Dry Sertraline HCl Milling loss

Sertraline HCl

milled Sertraline HCl Sifting loss

Sertraline HCl

Reactor

R-1027

(3000 L GLR)

Centrifuge

CF1011 (48")

DCRVD1402/

DCRVD1401

(1000 L/ 1000 L)

Multi mill

MM1401/

MM1402

Sifter SR1101

Jet mill

JM1401







MATERIAL BALANCE:

Stage I

INPUT

OUTPUT

Chemical name kg

Name Kg

sertraline mendate 1.52 Product 1.00

caustic soda pallets 0.30 As Emission 0.68

Ethyl Acetate

13.68 Hazardous

Waste

IPA HCL solution 0.96 Effluent 15.42

Water

13.64 Recovered

Solvent

13.00

As moisture 0








18) Nicorandil


Step-1: - Nico Ester

Cool the reaction mixture of Nicotinic acid, Toluene, DMF to 20-25°C. Then add Thionyl

Chloride & maintain temperature 20-25°C. Reflux the above mixture at 100 to 110°C till

absence of Nicotinic Acid at Acid Chloride stage. Distill out toluene. Cool the batch to 0-

5°C. Add methanol & reflux the batch at temperature 55-60°C till absence of Nicotinic

Acid at Nico-ester stage. Cool the batch to 15-20°C. Neutralise the reaction mixture.

Separate the toluene layer, after recovery of toluene. Residue is Nico-ester.

Step-2: - Nico Amide

Heat Nico-ester with mono ethanolamine at 95-110°C. Concentrate the reaction mixture

till no distillate is observed. Cool the batch to 50-55°C. Unload the Nico-Amide in water.

Step-3: - Nicorandil Crude

Nico-Amide added to Fuming Nitric Acid to give Nicorandil crude at temperature -1 to -

10°C. neutralize & then Centrifuge the reaction mass. Spin dry the Nicorandil Crude.

Step-4: - Nicorandil

Nicorandil crude is dissolved in IPA at 37-42°C. Twice charcolisation & filtration carried

out. After IPA distillation, reaction mass crystallise at 0-5°C. Reaction mass then filtered

through centrifuge and dried in DCRVD to get LOD & moisture content below 0.5%

Step-4: - Nicorandil JP

Nicorandil crude is dissolved in IPA at 35-40°C. Twice charcolisation & filtration carried

out. The Wet cake obtained is further dissolved in IPA at 35-40°C. Again twice

charcolisation & filtration carried out & After IPA distillation, reaction mass crystallise at 0-

5°C.

Reaction mass then filtered through centrifuge and dried in DCRVD to get moisture content

below 0.1%.







REACTION:







FLOW DIAGRAM:

Stage I Nico ester

Toluene

Nicotinic Acid Toluene Recovery

DMF

Thyonyl Aq.Layer

Methanol

PurifiedWater

Ammonia

Sodium Carbonate

Organic Mass

Toluene Recovery

Organic Mass Vapoure loss

Water Wash Aq.Layer

Nico Ester

Reactor R2001

(630 L) GLR

Reactor R2002

(750 L) SSR

Stage II Nico Amide

Nico Ester

Distilled Reaction Mass

Momo Ethanolamine

Vapoure loss

PurifiedWater

Nico Amide

Reactor R2002

(750 L) SSR







Stage III Nicorandil Crude

NitricAcid

Nico amide

Reaction Mass

PurifiedWater

Reaction Mass

Sodium Bicarbonate

Reaction Mass

ML

Reaction Mass

Wter wash Water wash

Nicorandil Crude

Reactor R2001

(630 L) GLR

Reactor R2101

(1600 L) GLR

Centrifuge

CF2001/2004

(48")







Stage IV Nicorandil

IPA

Nico Crude

Charcoal

IPAwashing

Reaction Mass

Reaction Mass

Wet Charcoal

Reaction Mass

Vapoureloss

Reaction Mass

PurifiedWater IPA Recovery

IPA washing

Wate rwash

Reaction Mass

Reaction Mass

ML

Wet Material

Wet Material Vapoure loss

Dry Material

Dry Material

Oversize sifted material

Reactor R2002

(750 L) SSR

Centrifuge

CF2001/2004

(48")

DCRVD 2001

(500 L)

Sifter SR 2001

(40 Mesh)

Reactor R2001

(630 L) GLR

Sparkler Filter

SF2001 (14")







MATERIAL BALANCE:

Stage I

INPUT

OUTPUT

Chemical name kg

Name Kg

Toluene 5.71 Product 1.00

NICO

ester


Nicotinic acid 0.94 Hazardous

Waste

0.00

Thionyl chloride 1.85 effluent 10.20

Dimethyl formamide 0.02 Recovered

Solvent

6.16

Sodium bicarbonate 0.38 As moisture

Water 6.60

Liquor ammonia lr grade 1.43

Total 17.69

Total 17.69

Stage 2

INPUT

OUTPUT

Chemical name kg

Name Kg

Nico

amide

STAGE 1 0.75 Product 1.00

Monoethanolamine 0.63 As Emission

Water 10.27 Hazardous

Waste

0.00

effluent 10.66

Recovered

Solvent

As moisture








Stage 3

INPUT

OUTPUT

Chemical name kg

Name Kg

Nico

amide

crude


Fuming nitric acid 5.28 As Emission 0.00

Sodium carbonate 4.72 Hazardous

Waste

0.00


Recovered

Solvent

0.00

As moisture


Stage4

INPUT

OUTPUT

Chemical name kg

Name Kg


Nicorandil Isopropanol (IPA) 12.86 As Emission 0.64

Activated charcoal 0.19 Hazardous

Waste

0.19


Recovered

Solvent

12.21

As moisture 0








19) TOLVAPTAN


Step-5: - Diamide Crude

Amino amide Pure is condensed with 2-methyl benzoyl chloride (acid chloride) in MDC &

Triethyl amine (TEA) at 25-30°C to give Diamide crude. TEA is used as a HCl scavenger.

The reaction is carried out at 25°C to 30°C temperature. The reaction completion is

monitored by TLC. On completion of reaction it is worked up by adding water to the

reaction mixture followed by extraction & distillation of MDC. Final isolation is carried out

by using methanol.

Step-6 – Diamide Pure

Diamide crude is purified by using methanol at 60-65°C and filtration at 5-10°C

Step-7: - Tolvaptan Crude

The Diamide Pure on reduction using sodium borohydride in water & methanol at 24-30°C

gives tolvaptan crude. The reaction completion is monitored by TLC. On completion

reaction is worked up by adding aq. HCL to the reaction mixture followed by filtration.

Step-8: - Tolvaptan

Finally, Tolvaptan crude is purified by crystallization in methanol and water at 60-65°C

and filtration at 0-5°C.







REACTION:







FLOW DIAGRAM:

Stage-V

Amino amide Pure

Aqueous Layer

Methylene Chloride ETP

Triethyl Amine

2-methyl benzoyl chloride

Water

Methanol

Reaction Mass

Reaction Mass

ML to ETP

Methanol

Wet cake


Dry Diamide Crude

Reactor

R1006

(225 L SSR)

Buckner Filter

BF1002 (30 L)

Tray Dryer

DR1401

(48 Trays)







Stage-VI

Diamide Crude Vapour Loss

Methanol

Reaction Mass

Reaction Mass

ML to ETP

Methanol

Wet cake


Dry Diamide Crude

Tray Dryer

DR1401

(48 Trays)

Reactor

R1006

(225 L SSR)

Buckner Filter

BF1002 (30 L)







Stage-VII

Diamide Pure Vapour Loss

Methanol

Water

Sodium Borohydrate

Conc. HCl

Reaction Mass

Reaction Mass

ML

Water

Wet cake


Dry Diamide Crude

Reactor

R1006

(225 L SSR)

Buckner Filter

BF1002 (30 L)

Tray Dryer

DR1402

(48 Trays)







Stage-VIII

Tolvaptan Crude Vapour Loss

Methanol

Activated Charcoal

Reaction Mass


Methanol

Hyzardous Waste (Charcoal & hyflo)

Hyflo super cel

Reaction Mass


Methanol

Rec. Methanol

Purified Water Sale

Reaction Mass

Reaction Mass

ML

Water

Methanol

Wet cake

Vapour Loss

Wet Cake

Dry wet

Dry material

Milling loss to ETP

Milled material

Milled material Sifting Loss to ETP

Tolvaptan

Reactor

R1006

(225 L SSR)

Buckner Filter

BF1002 (30 L)

Sifert

SF1401/ SF1402

(30")

Buckner Filter

BF1002 (30 L)

Reactor

R1017

(675 L SSR)

DCRVD Drying

DCRVD1401/

DCRVD1402

(1000 L)

Multimill

MM1401/

MM1402







MATERIAL BALANCE:

Stage I to 4 Taken At

Third party.

1. nitroamide 2.Amino amide with Iron 3. amino

amide crude 4. Amino amide Pure

Stage-5

INPUT

OUTPUT

Chemical name kg

Name Kg


Diamide

crude

2-Methyl Benzoyl

Chloride


Methylene Chloride (ST) 25.21 Hazardous Waste 0.00

Triethylamine 0.35 Effluent 26.24

Methanol 11.56 Recovered Solvent 35.27

water 25.75 As moisture 0


Stage 6

INPUT

OUTPUT

Chemical name kg

Name Kg

Diamide

pure Stage 5

1.12 Product 1.00


Hazardous

Waste

0.00

Effluent

Recovered

Solvent

10.13

As moisture 0








Stage7

INPUT

OUTPUT

Chemical name kg

Name Kg


Tolvapton

Crude Sodium Borohydride

0.13 As Emission

0.37

Hydrochloric acid 0.16 Hazardous

Waste

Methanol 7.32 Effluent 15.84

Water 15.43 Recovered

Solvent

6.96

As moisture 0


Stage8

INPUT

OUTPUT

Chemical name kg

Name Kg


Activated

Charcoal(Alkaline)

0.42 As Emission

1.78

Tolvapton Hyflo supercel (Celite)

0.83 Hazardous

Waste

1.25

Methanol 35.60 effluent 4.26

Water 3.88 Recovered

Solvent

33.82

As moisture 0








20) BENIDIPINE.HCL


2,6-Dimethyl-5-methoxy carbonyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3-carboxylic acid

(Monoester) is reacted with thionyl chloride and 1 Benzyl 3 Piperidinol in MDC, DMF, Methanol

and MEK to form 3-[(3RS)-1-benzylpiperidin-3-yl]5-methyl(4RS)-2,6-dimethyl-4-(3-

nitrophenyl)1,4-dihydropyridine -3,5-dicarboxylate monohydrochloride (Benidipine

Hydrochloride).

REACTION:







FLOW DIAGRAM:

Stage-I Benidipine Hydrochloride

Monoester

Aqueous Layer ETP (Effluent)

Methylene Chloride

Dimethyl formamide

ML (Org. layer) for sale

Thionyl Chloride

1- Benzyl 3- Piperidinol

Sodium Sulphate

Methanol

Methyl ethyl ketone

Water

Reaction mass

Reaction Mass


Methyl ethyl ketone

Wet cake

Wet cake Vapour Loss (Air Emission)

Benidipine hydrochloride

Reactor GLR

Buckner

Filter

Tray Dryer







MATERIAL BALANCE:

Stage I

INPUT OUTPUT


Monoester 2.00 Product 1.00

Methylene chloride 14.00 As

Emission

2.17

Dimethyl formamide 2.80 Hazardous

Waste

0.20

Thionyl chloride 0.55 Effluent 62.81

1-benzyl 3-piperidinol 1.26 Recovered

Solvent

41.33

Sodium sulphate 0.20 As

moisture

0

Methanol 1.70

Methyl ethyl ketone 25.00

Water 60.00








21) SOLIFENACIN


(1S)-1-Phenyl -1,2,3,4-Tetrahydroisoquinoline reacted with ethyl Chloroformate in toluene &

sodium bicarbonate to give (1S)-1-Phenyl-1,2,3,4 Tetrahydroisoquinoline-2-carboxylic acid ethyl

ester (Intermediate-I).

Intermediate-I reacted with R-Quinuclidinol in presence of Base & toluene to give Solifenacin

Base (Intermediate-II).

On reaction of Solifenacin base with succinic acid produce Solifenacin Succinate crude.

Succinate crude after purification gives final API – Solifenacin Succinate EP.

REACTION:







Stage-I Solifenacin Intermediate 1st

(1S)-1-Phenyl-1, 2, 3, 4-Tetrahydroisoquinoline


MDC

Triethyl amine

Ethyl Chloroformate

Water

Organic Layer (Reaction Mass)

Reaction Mass

Aq. HCl solution Aqueous Layer ETP (Effluent)

Calsium Chloride Haz Waste (Calsium Chloride solid)


Reaction Mass Vapour Loss (Air Emission)

Distilled Solvent (Solvent for sale)

Solifenacin Intermediate 1st

Reaction

SSR Reactor

Work up

(GLR / SSR)

Reactor

Concentration

SSR Reactor

FLOW DIAGRAM:







Stage-II Solifenacin Base

Solifenacin Intermediate 1st Vapour Loss (Air Emission)

R-Quinuclidinol Aqueous Layer ETP (Effluent)

Toluene

Sodium Methoxide

Water


Reaction Mass

Aq. HCl solution Aqueous Layer ETP (Effluent)

Aq. ammonia Solution Haz Waste (Sodium sulfate solid)

Sodium Sulfate




Solifenacin Base

Reaction

SSR Reactor

Work up

(GLR / SSR)

Reactor

Concentration

SSR Reactor







Stage-IIII Solifenacin Succinate Crude

Solifenacin Base

Succinic Acid

Ethyl Acetate

Reaction Mass

Vapour Loss (Air Emission)

Reaction Mass

ML (Solvent for sale)Ethyl Acetate

Wet cake

Wet Cake Vapour Loss (Air Emission)

Dry Solifenacin Succinate Crude

Reaction

SSR Reactor

Buckner Filter

DCRVD Drying







Stage-IV Solifenacin Succinate

Solifenacin Succinate Crude

Aqueous Layer ETP (Effiuant)

Ethyl Acetate

Aq. ammonia Solution

Aq. NaCl Solution Haz Waste (Sodium sulfate solid)

Sodium Sulfate




Solifenacin Base

Solifenacin Base

Succinic Acid

Ethyl Acetate

Reaction Mass


Reaction Mass

ML (Solvent for sale)

Ethyl Acetate

Wet cake


Wet Cake

Dry Solifenacin Succinate

Dry material

Milling loss (Air Emission)

Milled material

Milled material Sifting Loss (Air Emission)

Solifenacin Succinate

Reaction

SSR Reactor

Buckner Filter

DCRVD Drying

Multimill

Sifert

Reaction &

Work up

(GLR / SSR)

Reactor

Concentration

SSR Reactor







MATERIAL BALANCE:

INPUT OUTPUT


S-1-phenyl-1,2,3,4 tetra hydro iso-

quinoline

0.83 Product 1.00

MDC 4.50 As Emission 0.22

Ethyl chloroformate 0.47 Hazardous

Waste

0.50

TEA 0.44 Effluent 12.02

Conc. Hcl solution 0.41 Recovered

Solvent

4.28

Sodium chloride 0.50 As moisture 0

Water 10.37

Calcium chloride 0.50


Stage II

INPUT OUTPUT


STAGE -1 1.11 Product 1.00

DMF 1.12 As Emission 0.86

Toluene 16.00 Hazardous

Waste

0.45

R-quinuclidinol 1.00 Effluent 20.99

Sodium methoxide 0.42 Recovered

Solvent

16.26

Ethyl acetate 6.50 As moisture 0

NACL 0.36

Conc. Hcl 0.90

K2CO3 1.10

Water 10.60

Sodium sulphate 0.45








STAGE III

INPUT OUTPUT

CHEMICAL NAME KG NAME KG

STAGE - II 1.43 Product 1.00

Ethyl acetate 6.44 As emission 0.32

Succinic acid 0.42 Hazardous

waste

0.00

Effluent 0.85

Recovered

solvent

6.12

As moisture 0

TOTAL 8.29

TOTAL 8.29

Stage IV

INPUT OUTPUT


STAGE-III 1.22 Product 1.00


K2CO3 0.61 Hazardous

Waste

0.60

Sodium sulfate 0.60 Effluent 8.20

Ethyl acetate 4.50 Recovered

Solvent

11.88

Succinic acid 0.37 As moisture 0

Water 7.00








22) Cinacalcet.HCl


3-Trifluoromethyl Aniline is treated with Allyl alcohol, Sodium nitrite, acid, Palladium and

sodium bisulphite in Acetonitrile, Toluene and water to form 3-[3-(Trifluoromethyl) Phenyl]

Propanol adduct (FMPP adduct).

FMPP adduct is treated with (R)-(+)-1-(1-form N-[1-(R)-(-)-(1-naphyl)ethyl]-3-[3-

(trifluoromethyl)phenyl]-1-aminopropane (Cinacalcet Hydrochloride).

REACTION:







FLOW DIAGRAM:

Stage-I 3-[3-(Trifluromethyl) Phenyl]Propanal adduct

3-trifluro methyl aniline

Aqueous Layer ETP

(Effluent)

Conc. Sulphuric acid

Sodium Nitrite

Palladium acetate

Allyl alcohol

Sodium Bisulphite

Sodium chloride

Acetonitrile

Toluene

Water

Reaction mass

Reaction Mass


Water

Wet cake


1.0 Kg Stage- I

Reactor GLR

Buckner Filter

Tray Dryer







Stage-II Cinacalcet Hydrochloride

Stage I Aqueous Layer ETP (Effluent)

Sodium hydroxide

Sodium Chloride ML (Org. layer) for sale

Sodium Sulphate

Ethyl amine

Sodium triacetoxy borohydride

Hydrochloric acid

Methanol

Methylene Diachloride

Ethyl acetate

Water

Reaction Mass

Reaction Mass


Ethyl acetate

Wet cake


1 Kg Dry Cinacalcet

Hydrochloride

Reactor GLR/SSR

Buckner Filter

Tray Dryer







MATERIAL BALANCE

Stage I

INPUT OUTPUT


3-trifluoro methyl aniline 1.35 Product 1.00

Conc. Suphuric acid 3.00 As Emission 1.10

Sodium nitrite 0.72 Hazardous

Waste

0.00

Palladium acetate 0.01 Effluent 33.65

Allyl alcohol 0.57 Recovered

Solvent

20.90

Sodium bisulphite 1.33 As moisture 0

Sodium chloride 0.67

Acetonitrile 7.00

Toluene 15.00

Water 27.00


Stage 2

INPUT OUTPUT


Stage I PRODUCT 1.83 Product 1.00

Sodium hydroxide 1.50 As Emission 2.37

Sodium chloride 0.90 Hazardous

Waste

0.18

Sodium sulphate 0.18 effluent 47.89

Ethyl amine 0.83 Recovered

Solvent

45.13

Sodium triacetoxy borohydride 1.83 As moisture 0

Hydrochloric acid 9.00


Ethyl acetate 35.00

Methanol 3.50

Water 33.00








2.6 Raw material required along with estimated quantity, likely source, marketing

area of final Product/s, mode of transport of raw material and finished product

Raw Materials:

The detailed raw material list for proposed products as per selected capacity is detailed

below for all reactants, solvents and support chemicals.

Source for Raw Material Procurement:

Raw Materials are easily available in the local market, from Mumbai and Gujarat. Part of

the raw materials are generated In-house and used internally and some raw material will be

imported Viz.

Mode of Transport of Raw Materials: Raw Material and finished goods will be transported

through Trucks/ Tankers.

Storage at the site: Raw Materials will be stored in storage yard at the project site. Location of

storage yard is demarcated in Layout Plan.







Table 2-3: Details of Raw material Quantity

Sr.

No.

Chemicals / Items Unit Capacity Consum

ptions

in Kg.

per

Annum

Storage Physical

State

(Solid /

Liquid /

Gas)

Max.

qty.

stored

at any

point

of

time

Source

of

Supply

Means of

Transport

(By Road

/ Ship

/ Air)

1 (2-(2,3-

Dichlorophenyl)-

Guanidinoimino)

KG 500 1360 Small

drum

Solid 400 Local By Road

2 (S)-methyl 2-(2-

chlorophenyl)-2-(6,7-

di

KG 250 350 Small

drum


3 10% palladium on

charcoal

KG 10 8 Small

drum


4 2 - amino pyridine KG 150 550 Small

drum


5 2-chloromethyl-3,4-

dimethoxy pyri hydro

KG 500 5878 Small

drum


6 2-furoic acid KG 500 1550 Small

drum


7 4 bromo 2-2 diphenyl

butyro nitrite

KG 500 2874 Small

drum


8 4-(2-4-Difluoro

benzoyl oxime)-

piprodine

KG 200 960 Small

drum


9 4-chloro phenyl

4hydroxy

piperidine(CPP)

KG 500 2555 Small

drum


10 5-difluromethoxy-2-

mercapto-1h-

benimidaz

KG 500 5763 Small

drum


11 5Chloro1methyl1H-

imidazole Nitrate

NonEx

KG 200 1001 Small

drum


12 70 % sulphuric acid

CP

KG 200 200 carboy Liquid 200 Local By Road

13 Acetic acid glacial KG 250 1175 carboy Liquid 235 Local By Road

14 Acetone KG 22000 110770 big drum Liquid 9980 Local By Road

15 Acetonitrile KG 800 4000 big drum Liquid 640 Local By Road

16 Activated carbon KG 400 3970 BAG Solid 360 Local By Road

17 Alpha acetyl gamma

butyrolactone

KG 500 960 big drum Liquid 480 Importe

d

By Ship

18 Amino amide pure KG 10 9 Small

drum


19 Ammonium sulphate KG 1500 13950 BAG Solid 1500 Local By Road

20 Caustic potash flakes KG 500 2200 BAG Solid 400 Local By Road

21 Caustic soda flakes KG 1500 6200 BAG Solid 1200 Local By Road

22 Caustic soda lye KG 10000 88251 tank liquid 8126 Local By Road







23 Caustic soda pallets KG 100 300 Small

drum


24 Chloro fluoro

butyrophenone(CFB)

KG 500 1800 big drum Liquid 360 Local By Road

25 Chloroform KG 2000 11480 big drum Liquid 2000 Local By Road

26 Commercial Hydrogen

cylinder

NO 10 49 cylender Gas 10 Local By Road

27 Commercial Nitrogen

cylinder


28 Decanoic acid (N-

capric acid)


29 Denatured absolute

alcohol (5% acetone)

L 10000 31000 big drum Liquid 10000 Local By Road

30 Di-isopropyl amino

ethyl chloride HCL

KG 150 403 Small

drum


31 Dichloro acetyl

chloride

KG 1000 2500 big drum Liquid 1000 Importe

d

By Ship

32 Diethanolamine KG 800 1890 big drum Liquid 630 Local By Road

33 Diethyl oxalate KG 2000 10250 big drum Liquid 1750 Local By Road

34 Dimethyl formamide KG 2090 12470 big drum Liquid 2090 Local By Road

35 Ethyl acetate KG 5000 47670 big drum Liquid 4200 Local By Road

36 Fuming nitric acid KG 1000 3150 carboy Liquid 645 Local By Road

37 Glycerine KG 2500 12000 big drum Liquid 2500 Local By Road

38 Hexane L 10000 21600 big drum Liquid 2400 Local By Road

39 Hydrobromic acid

(aqueous 48%)


40 Hydrochloric acid KG 2500 53860 carboy Liquid 2070 Local By Road

41 Hyflo supercel (Celite) KG 250 1042 BAG Solid 250 Local By Road

42 Hypoxanthine KG 500 6000 Small

drum

Solid 500 Importe

d

By Ship

43 IS, CIS-Sertraline

Mandelate

KG 400 2000 Small

drum


44 Iso propyl alcohol KG 5000 4800 big drum Liquid 1280 Local By Road

45 Isopropyl alcohol HCl

solution (20%)


46 Isopropyl ether KG 5000 19500 big drum Liquid 3800 Local By Road

47 Liquor ammonia L 1000 11600 carboy Liquid 800 Local By Road

48 MCA Solution KG 25 200 carboy Liquid 25 Local By Road

49 Methanol KG 22000 169192 tank liquid 10480 Local By Road

50 Methyl bromide pure KG 60 420 cylender Gas 60 Local By Road

51 Methyl ethyl ketone KG 1500 5440 big drum Liquid 1155 Local By Road

52 Methylene chloride KG 20000 153630 big drum Liquid 16320 Local By Road

53 Mincare solution L 20 60 carboy Liquid 20 Local By Road

54 Mono methylamine KG 2000 12820 big drum Liquid 1870 Local By Road

55 Nicotinic acid KG 200 450 Small

drum


56 Nitric acid LR grade KG 600 3950 carboy Liquid 600 Local By Road

57 P-chloro nitro benzene KG 500 2250 BAG Solid 450 Local By Road







58 Para anisidine KG 1000 2900 BAG Solid 725 Local By Road

59 Para toluene

sulphonyl chloride

KG 1500 4050 BAG Solid 1350 Local By Road

60 Phenyl acetonitrile

(Benzyl Cyanide)


61 Phosphorous

oxychloride


62 Phosphorous

pentachloride


63 Pyridine KG 3500 24675 big drum Liquid 3150 Local By Road

64 Raney nickel KG 100 360 Small

drum

90 Local By Road

65 Rec isopropyl ether KG 5000 69890 big drum Liquid 4800 Local By Road

66 Recovered MDC KG 10000 55943 big drum Liquid 9000 Local By Road

67 Recovered Toluene KG 10000 30417 big drum Liquid 4500 Local By Road

68 Reprocess - 10%

palladium on charcoal

KG 10 17 Small

drum


69 Sodium bi carbonate KG 1500 8000 BAG Solid 1500 Local By Road

70 Sodium Borohydride G 2000 2000 BAG Solid 2000 Local By Road

71 Sodium Carbonate KG 1300 26100 BAG Solid 1300 Local By Road

72 Sodium chloride KG 1100 3950 BAG Solid 1100 Local By Road

73 Sodium hypochlorite KG 3000 31020 carboy Liquid 2400 Local By Road

74 Sodium meta bi

sulphite

KG 50 150 BAG Solid 50 Local By Road

75 Sodium Sulphate KG 1000 7500 BAG Solid 1000 Local By Road

76 Sodium thiosulphate KG 200 800 BAG Solid 200 Local By Road

77 Sulphuric acid CP KG 1500 8950 carboy Liquid 1500 Local By Road

78 Sulphuric acid L.R. KG 1700 23850 carboy Liquid 1700 Local By Road

79 Tetra butyl

ammonium bromide

KG 200 355 Small

drum


80 Thionyl chloride KG 1800 5700 big drum Liquid 1800 Local By Road

81 Toluene KG 22000 82098 tank liquid 4870 Local By Road

82 Triethylamine KG 500 1800 big drum Liquid 450 Local By Road

83 Trimethyl ortho

formate


84 Ultra High Purity

(UHP)Nitrogen

Cylinder


85 Xanthalene-9-

carboxylic

(xanthanoic)acid

KG 150 405 Small

drum

Solid 125 Importe

d

By Ship







2.7 Resource optimization/recycling and reuse envisaged in the project

Most energy efficient technology is already selected and implemented at existing unit and same

will be used in proposed modernization.

2.8 Availability of water its source, energy/power requirement and source

2.8.1 Water Requirement and Source

Total fresh water requirement after modernization of the project for domestic and industrial

activity during operation phase will be 350 CMD. The water supply is from MIDC. The details of

water requirement are given in Table 2-4

Table 2-4: Details of Raw water consumption

Sr. No. Units Existing requirement

CMD

A Domestic 70

B Process 160

C Utilities

1 Cooling Tower 40

2 Boiler 20

D Gardening 60

Total 350

2.8.2 Power Requirement

Power requirement for project made available through State Electricity Board. Present Power

sanctioned load is 2975 KW which is sufficient for proposed modernization. No additional

power will be required for modernization.

2.8.2.1 Emergency power

Electric Supply of MSEDCL is available through two different feeders where regular power supply

is available. In rare case D. G. set of 625 KVA capacity is run when MSEDCL takes planned power

shut down. For proposed project no additional D G sets will be required.







2.8.3 Fuel Requirement

Equipment Fuel Quantity required at

full load

Existing Boiler

1 No 2 TPH PNG/FO (Optional)

41.6 SCM/hr. or

41 .6 Kg/hr.

Existing D G

1 no X 625

KVA

HSD 104 kg/hr.

2.9 Quantity of wastes to be generated (liquid and solid) and scheme for their

management/disposal

2.9.1 Gaseous Emissions

Details of gaseous emissions from Process and Flue gas are given in Table 2-5

Table 2-5: Details of emissions from process and flue gas

Note: Boiler is running on PNG, in case of emergency only boiler will run on FO.

Emission rate given is based on 100% fuel consumption

S. No. Pollutant Source of

Emission Emission rate

1. SO2 Existing Boiler 3.71 Kg/hr

2. SO2 Existing DG 0.52 Kg/hr







Details of stack mitigation measures are given in Table 2-6.

Table 2-6: Details stacks along with their mitigation methods

Attached to

Boiler DG KVA Process stacks

(Scrubber 5 Nos.)

Existing Existing Existing

Capacity 2 TPH 625 KVA NA

Fuel type PNG/ FO (Optional) HSD NA

Fuel Quantity 41.6 SCM/hr. or

41.6 Kg/hr. 104 Kg/hr. NA

MOC MS MS MS

Shape Round Round Round

Gas temperature 145 oC 40 oC NA

Stack Height stack - 33.3 M 10 M from

ground 10 m each

Mitigation

Measures Stack Stack Stack







2.9.2 Effluent

The quantity of effluent generated proposed project is given in Table 2.7

Table 2-7: Details of Effluent Generation

S. No. Units

Effluent generation

Qty.

Existing

A Domestic 60

B Process 108

C Utilities

1 Cooling water 8

2 Boiler 4

D Gardening -

Total

180







Existing Treatment Scheme for Trade Effluent

Effluent after passing through the BAR SCREEN CHAMBER & OIL – GREASE SEPERATOR for the

removal of large floating debris, and oil & grease respectively. The effluent is then collected in to

NEUTRALIZATION TANK by gravity. Air blower with piping grid is provided for mixing & to avoid

the settling of suspended solids. Lime slurry & Mineral acids are used for neutralization. The

neutralized effluent is collected in to EQUALIZATION TANK for homogenation. The effluent is

further drawn by gravity to fill and draw type flash mixer tanks where 5% Non-Ferrous Alum

treatment is given. The effluent then pumped to STATIC MIXER at constant rate where

Polyelectrolyte (Megnafloc 0.01%) solution is dosed before effluent enters in CLARIFIER–1. The

flocculates & coagulated colloidal particles formed are removed to SLUDGE HOLDING TANK. The

supernatant of the effluent from CLARIFIER–1 is then directed to SOLID SETTLING TANK for

stabilization of organic load before feeding to Biological system. The effluent from Solid Settling

Tank is then feed by gravity to AERATION TANK–1 for biodegradation of organic matters (BOD &

COD). The Aeration Tank–1 overflow is collected in launder–1 where from effluent is pumped to

CLARIFIER–2. The supernatant of the effluent from CLARIFIER–2 is then directed to AERATION

TANK–2. The Aeration Tank–2 overflow is collected in launder–2 where from effluent is pumped

to CLARIFIER–3.

The sludge settled in Clarifier–2 & 3 is partly recycled to Aeration Tank–1 & 2 respectively to

maintain required MIXED LIQUOR SUSPENDED SOLIDS (MLSS). The remaining part of the sludge

is collected in to SLUDGE HOLDING TANK for feeding to FILTER PRESS using screw Pumps. The

semi dry sludge is collected in to bags for disposal to CHWTSDF. The supernatant of the effluent

from Clarifier–3 is collected in to FILTER FEED TANK where from effluent is feed to SAND FILTERS

and further to CARBON FILTER in series for Water polishing. The outcome is collected in to

TREATED EFFLUENT COLLECTION TANK for backwash, else it proceeds to VEE NOTCH TANK by

gravity for final discharge to TBIA CETP through MIDC sewerage lines. Appropriate dosing of Air

(Oxygen) from blower unit is provided to Aeration Tanks through tubular type membrane

diffusers to maintain dissolved oxygen level & keep bacterial culture alive. External dosing of

nutrients like Micronutrients, DAP, Jaggry is given to Aeration Tanks as per recommended by

Environment Consultant for healthy growth of bacteria. As per CPCB guidelines, A REAL TIME

ONLINE EFFLUENT MONITORING SYSTEM is installed at “VEE” notch where from monitoring data

of discharge effluent is continuously being uploaded to MPCB & CPCB server.







Trade Effluent : To ETP

Table 2-8: ETP Characteristics

Sr.

No. Parameters

Inlet Effluent

Characteristics

(Mg/Lit )

Outlet Effluent

Characteristics

(Mg/Lit)

Effluent discharge

standards (MPCB)

(Mg/Lit )

1 pH 9.5 7.6 5.5 to 9.0

2 COD 9070 154.3 250

3 BOD (3 days at 27 OC) 3847 52.5 100

4 TSS 1831 58.9 100

5 TDS 2735 772.8 2100

6 Oil & Grease 11.4 < 0.1 10







Existing Effluent Treatment Plant







Treatment Scheme for Domestic Wastewater

The domestic waste water generated will be treated septic tank followed by combined

treatment in ETP.

2.9.3 Details of Hazardous wastes

The types of Hazardous wastes generated from the project, method of disposal is shown in

below table 2.9

Table 2-9: Details of Hazardous Solid waste along with the Category and disposal

method

Sr.

No.

Waste

Category

No.

Type of Waste Quantity in MTA

Existing

Packing Disposal

1 3.3 Sludge & Filters

contaminated with

oil

5.4 H.D.P.E. Drums CHWTSDF

2 5.1 Used / Spent Oil 1.44 H.D.P.E. Drums Sale to

authorized

recyclers /

CHWTSDF

3 20.3 Distillation Residue 5.4 H.D.P.E. Drums CHWTSDF

4 28.1 Residue & Wastes* 134.4 H.D.P.E. Drums Sale to

authorized

recyclers /

CHWTSDF

5 28.3 Spent Catalyst /

Spent Carbon

30.0 Polythene Bags CHWTSDF

6 28.4 Off Specification

Products


7 28.5 Date expired,

discarded & off

specification drugs


8

28.6

Spent Solvent

384.0

M.S. & H.D.P.E

Drums

Reuse / Sale to

MPCB

authorized party

/ CHWTSDF

9 33.1 Discarded

containers / Barrels

/ Liners

24.0 Polythene Bags Reuse / Sale to

MPCB

authorized party

/ CHWTSDF

10 35.2 Spent Ion

Exchange Resin

containing Toxic

Metals


11 35.3 Chemical sludge

from waste water

50.0 Polythene Bags CHWTSDF







treatment

12 35.4 Oil & Grease

skimming residues


13 Used Batteries 0.360 Polythene Bags Returned to

battery

manufacturer

through

authorized

dealer on buy

back

procurement

14 E-Wastes 1.2 Polythene Bags Sale to

authorized E-

Waste

dismantlers /

Recyclers.

Non- Hazardous Waste:

Sr.

No.

Type of Solid Waste

generated UOM Existing Mode of Disposal

1 Paper, Wood, Plastic and

Metals MTA 18 Sale to authorized party

2

Discarded, Detoxicated

containers / Barrels

(M.S./HDPE Drums 200 Ltrs.

Cap.)

Nos./A 684 Reuse / Sale to authorized

party

3

Garbage like Paper,

Corrugated Boxes, Plastics,

Fibre drums, Brooms, Wipers,

Floor cleaning mops, Tea cups,

disposable approns, head caps

& shoe covers etc.

MTA 36 Sale to authorized party







2.10 Schematic representations of the feasibility drawing which give information of

EIA purpose.

Project Identification

What environmental impacts are normally associated with such type of projects being

proposed?

Pre-feasibility Analysis

Is the Project feasible from an environment point of view?

Project Design

(a) What negative environmental impacts could arise if the proposed project is implemented

with proposed design?

(b) Is there alternative design with less environmental impacts?

Project Appraisal

Have all the environmental concerns associated with the project been eliminated?

Project Implementation

What environmental concerns might arise at the implementation phase of the project?

Preparation of an Environment Monitoring and Evaluation Plan

(a) What environment monitoring indicators are required to ensure that the

implementation of components of the project will be executed within

environmentally sound limits?

(b) What is required to ensure that the recommended environmental control

measures will be implemented and enforced?

(c)

(Prepare a comprehensive environment monitoring and management plan)

Post EIA Monitoring and Environment Audit

(a) Is the implementation of components of the project being executed in an

environmentally sound manner?

(b) Are all the recommended environmental control measures being implemented and

enforced?

(d) Are there any environmental impacts that were earlier not anticipated when EIA was

done?

( Identify gaps and corrective action )







3.0 SITE ANALYSIS

3.1 Connectivity

Proposed unit is planned at Plot No. 25, TTC MIDC, Navi Mumbai, Maharashtra.

The nearest city from the site is Turbhe at 1 Km & Thane at 15 Km

The nearest railway station is Turbhe at 1 Km and Thane at 15 Km

The nearest airport is at Mumbai at 30 km.

Site is well connected to Thane Belapur road which connects to Mumbai Goa highway and

Mumbai Bangalore highway.

3.2 Land Form, Land use and Land ownership

The proposed land is situated in approved chemical zone of MIDC where land use is industrial.

Land is owned by MIDC and is leased for 99 years.

3.3 Topography

The proposed industry is located at Latitude – 19.087864° N and Longitude- 73.018340° E

Elevation above mean sea level is: 12 m (40 ft.). Toposheet of the site is shown below. The study

area (10 km radius) around the project site exhibits flat terrain.







Figure 3.1: Top sheet Showing Project site and 10Km of area







3.4 Existing land use pattern (agriculture, non-agriculture, forest, water bodies

(including area under CRZ), shortest distances from the periphery of the project to

periphery of the forests, national park, wild life sanctuary, eco sensitive areas, water

bodies (distance from HFL of the river), CRZ.

Proposed site falls under the Industrial MIDC. The land is reserved for Industrial use.

Thane creek is at 3.5 km away from the site.

3.5 Soil classification

The basic type of soil found in the area varies from brown & black. The black type of soil is

found in the eastern part. The fertility of the soil increases as it goes from red to black.

3.6 Climatic data from secondary sources

The climate in proposed area is characterized by hot summer and general dryness throughout the

year except the south west monsoon season.

Climate Classification: Project site features a semiarid climate.

Temperature: Annual maximum and minimum temperature in Thane range from max. 38oC mini.

11oC. The most comfortable time to visit in the winter October to February.

Rainfall: Most of the rainfall occurs in the monsoon season from June to September. Average

annual rainfall is 2488 mm.

3.7 Social Infrastructure Availability

Key infrastructure such as hospitals, schools, bank, places of worship and social/

community facilities such as park, market, playground etc. education, health care, community

development, income distribution, employment and social welfare are available in nearby area

of Maharashtra Industrial Estate.







4.0 Planning In Brief

4.1 Planning Concept

MIDC Industrial area, TTC provides many basic facilities like uninterrupted water

supply, power and road network & solids disposal facility if feasible. When various sites were

seen, this site appeared to be environmentally best as also from the business angle and

therefore this option was finally adopted. This site is inside the campus of the MIDC and

means safe transportation, less need of Utilities, less constructing buildings and roads, less

fuel, less water with optimization of infrastructure.

4.2 Land Use Planning

Existing land is already developed and located in a designated industrial area. The total

plot area is 34483 sq.m.

Table 4-2: Land Use Break Up

Sr. No. Area Sq. m. %

1. Area used for manufacturing 3398 9.9

2. Area used for storage of raw materials/products 2560 7.4

3. Area used for storage of Hazardous & No-hazardous

Waste 324

0.9

4. Area used for utilities (Boilers, Thermopacks,

chimneys, D G sets, Cooling towers, ETP and STP) 1576

4.6

5. Administrative Building (Including offices, security,

Excise office) 975

2.8

6. Area Used for R&D Plant 519 1.5

7. Area used for internal roads 6500 18.8

8. Open area 1892 5.5

9. Area used for green belt development 12414

36% of

Total plot

area

10. Area provided for Parking 4325 12.5% of

total area

Total 34483 100%







4.3 Assessment of Infrastructure Demand (Physical & Social)

Key infrastructure such as hospitals, schools, bank, places of worship and social/

community facilities such as park, market, playground etc. education, health care, community

development, income distribution, employment and social welfare are available in nearby area

of Maharashtra Industrial Estate.

4.4 Amenities/Facilities

In proposed site many basic facilities like uninterrupted water supply, Power and Road

Network & solids disposal facility if feasible are available. This site is inside the campus of the

MIDC and means safe transportation, less need of utilities, less constructing buildings and

roads, less fuel, less water with optimization of infrastructure and networking with CHWSTDF

(Common Hazardous Waste Storage Treatment and Disposal facility), Taloja, in vicinity

established with support of MIDC and MPCB.

All nearby villages are provided with drinking water from wells or Government Water

Supply Schemes RWS. Hence we do not encroach upon their supply.

4.5 Population Projection

Thane has a population of 21,00,000 as per census 2011. It has more than 99,652 households of

Maratha, Aagri, Koli, Muslim, Buddhist, and also includes SC, ST, OBC and open categories

community.

Population growth is being increased at alarming rate with their basic requirements. Amongst,

Medicine is one of the basic need, which is very essential for everyone to live happy life. So to

fulfil their future basic need of Medicine for social community there is a necessity to promote R &

D Centre in each industrial sector. There will be in ratio of population increase in similar way

their need also increases so to fulfil their needs we are going to set up a proposed unit which

again generates employment.







5.0 Existing infrastructure

5.1 Industrial area

Industrial Area (Processing area)

Utilities

Cooling tower

HSD unloading/storage area

Boiler

Non- Processing Area

Safety Gallery

Weighbridge

Administrative Cabins

Security cabins

Workers restroom

Water reservoirs

Temporary storage sites

Works block etc.

Canteen

5.2 Residential Area

Residential area located near to the project site

5.3 Green Belt

The project is built on an MIDC plot with plot area of 34483 sq. m and Existing

green belt area is 12414 sq. m, which is 36% of total plot area, there are around 3585

nos. of trees and shrubs already planted at the site.

5.4 Social Infrastructure

The basic amenities within the study area include primary schools, dispensaries,

water supply, electric supply, public telephones, hotels, banks, post offices, petrol

pumps, bus services, technical training institute and entertainment etc.







5.5 Connectivity

Proposed unit is planned at Plot No. 25, MIDC Land, Thane-Belapur Road, Pawne, Navi

Mumbai, Maharashtra.

The nearest city from the site is Turbhe at a distance of 1 Km & Thane at 15 Km

The nearest railway station is Turbhe at 1 Km and Thane at 15 Km

The nearest airport is at Mumbai at 30 km.

Site is well connected to thane Belapur road which connects to Mumbai Goa national highway

(NH 66) and Mumbai Bangalore national highway (NH 4).

5.6 Drinking Water Management

The source of water supply is from MIDC.

5.7 Sewage System

The domestic waste water generated is being treated in septic tank followed by

combined treatment in ETP.

5.8 Industrial Water Management

Trade effluent is being treated in full fledge ETP having capacity of 180 CMD and

treated effluent sent to CETP.

5.9 Solid Waste Management

Hazardous solid waste generated from the process is being collected, stored,

transported and sent to CHWTSDF as per Hazardous waste (Management, Handling and

Transboundry Movement) Rules 2008.

5.10 Power Requirement & Supply / source

Present Power sanctioned load is 2975 KW which is sufficient for proposed

modernization. No additional power will be required for modernization.







6.0 Rehabilitation and Resettlement (R & R) Plan

6.1 Policy to be adopted (Central/State) in respect of the project affected persons

including home oustees, land oustees and landless.

This project does not require acquisition of land and the infrastructure. Hence, there is

no any kind of activity of Rehabilitation and resettlement carried out over it.







7.0 PROJECT SCHEDULE & COST ESTIMATES

7.1 Likely date of start of construction and likely date of completion

The Modernization with change in product mix activity is likely to start after getting

Environmental Clearance and NOC/CTE from the authorized committee.

7.2 Estimated project cost along with analysis in terms of economic viability of the

project

The total investment envisaged is Rs 81.10 Crs with the break-up as given below Table

7-3

Table 7-3: Cost Break-Up

Sr.

No. Particulars

Existing

(Cost in Cr.)

1 Land 21.24

2 Building & Premises 18.64

3 Plant and Machinery & Equipment 39.22

4 Environmental Management 2.00

Total Cost 81.10

7.3 Economic Viability

The project has been conceived assuming that there will be a growth in demand for the

proposed products, leading to a reasonable rate of return in the medium term. The project

is considered „bankable‟.







8.0 ANALYSIS OF PROPOSAL (FINAL RECOMMENDATIONS)

Proposed modernization activity will provide benefits to the local people in terms of

financial and social welfare.

Local people will get indirect income through contract of supply, services and transport.

Company will contribute in improving education and health awareness in nearby area.

Major business rise is expected to raw material suppliers which will reflect an increase in

employment and business.

Proposed modernization project can be done without any impact on environment and

infrastructure.







Annexure –I

Plant Layout

rpg lifesciences ltd. change in product mix for … · m/s rpg life sciences ltd. proposed project...

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