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PRE

M/s.Venkata Narayana Active Ingredients Private Limited

(Formerly M/s.Nutra

(Expansion of Production Capacities

Chandrapadiya Village, Vinjamur Mandal,

M/s. SV ENVIRO LABS & CONSULTANTSENVIRO HOUSE, BLOCK

VISAKHAPATNAM (Dt), ANDHRA PRADESH

QCI No: 14

1

PRE-FEASIBILITY REPORT

For


(Formerly M/s.Nutra Specialities Private Limited)

(Expansion of Production Capacities for Existing Products)

At


SPSR Nellore District,

Andhra Pradesh

Submitted by

M/s. SV ENVIRO LABS & CONSULTANTSENVIRO HOUSE, BLOCK-B, B-1, IDA, AUTONAGAR,


QCI No: 148, MoEF & NABL Recognized Laboratory


Specialities Private Limited)

Existing Products)


M/s. SV ENVIRO LABS & CONSULTANTS , IDA, AUTONAGAR,


NABL Recognized Laboratory

2

EXECUTIVE SUMMARY

1.0 Introduction:

Venkata Narayana Active Ingredents Pvt Ltd (Formerly Nutra Specialities Private

Limited) promotes by a well known business house of South India,which has vast

experience in Pharma industry for more than four decades. VNAI is one of the

fatestgrowing Pharmacuetical companies in India combining the power of Science &

Technology.

Established in 2007 and head quartered in Chennai, the state of the art manufacturing

facility and is strategically located near Nellore in Andhra Pradesh with the ease of access

to port town of Krsihnapatnam.

By virtue of the niche focus the company has registered an impressive growth over the

years and has gained significant market presence in API.VNAI is poised to grow rapidly,

with infrastructure capabilities to support development of advance intermediates and

CRAMS( Contract Research And Manufacturing Services).

The industry is committed to keep up the tradition of deleviring value to the customers

beiong the heart of corporate focus.

The management team is being headed by Managing Director AbhayaKumar , Director

V.S.Pattabiraman, Plant Head Dr. Ramakrishna Reddy and Marketing Head Sunil Baffna.

The industry is well equipped with glass lined and stainless steel reactors, driers ,

centrifuges, blenders and millers, dedicate ventilation systems etc.The industry is

accrideated and approved by US FDA ,ISO 9001-2015 certified. The industry maintains a

good EH & S policy for employee welfare, Environment Management , Social

Resposibiliy, Sustainable procurement.

3

1.1 Background:

M/s. Venkata Narayana Active Ingredients Private Limited ( Formerly Nutra Specialties

Private Limited) is in operation in Chandrapadiya Village, Vinjamur Mandal, SPSR

Nellore since 2007. The unit obtained Environmental Clearance in February, 2009 for

expansion from 60.72 TPA to 142.32 TPA vide order no: F.No.J-11011/1313/2007-IAII(I)

Dated: 02.02.2009. The industry obtained CFE for an annual capacity of 36 TPA in the

month of April, 2010 ( for any 4 products of 15 products proposed). The unit obtained

CFO of the Board in the month of December, 2012 for the same with a validity date of

31.05.2013. The Company has also obtained CFO vide dated 16th June, 2016 and this is

valid till 31st May, 2021.

The industry had obtained CFE for 24 products with overall production capacity of 142

TPA vide CFE Order No. 174/APPCB/CFE/RO-NLR/HO/2011 Dt: 01.02.2016 and

obtained CFE product mix for interchanging of three products vide order No.

174/APPCB/CFE/RO-NLR/HO/2011 Dt: 28.05.2016.

Again the industry obtained CFE Change of product mix by replacing 10 existing

products with 12 new products and by changing by products quantity without increasing

the overall production capacity of 142.32 TPA and obtained CFO. After that the industry

has obtained CFE for change of product mix with 31 products vide order

no.174/APPCB/CFE/RO-NLR/HO/2011 Dt: 08.02.2018 and in view of market demand

the industry obtained change of product mix by adding 4 new products by changing

quantity of existing products without increasing overall production capacity of 142.32

TPA mentioned in Environmental Clearance for which the industry obtained CFE vide

order number:174/APPCB/CFE/RO-NLR/HO/2011 Dated:17/09/2018 and CFO for the

same vide order no: APPCB/VJA/NLR/10725/HO/CFO/2018 Dated:14.12.2018 for 35

products.

All the changes in product mix approvals are obtained from SPCB without any increase

in the previously granted over all total limits as per the EC Expansion obtained and are

in same category as per the circular from MoEF & CC vide order no: F.No.J-

11013/41/2006-IA-II(I) Dated:14.12.2006

4

Now the industry proposes to expand their exisiting product capacities of Bulk drug and

intermediates manufacturing with increase in machinery and change in process

technology within the existing site premises.

As per the EIA Notification, published in Gazette of India, Extraordinary Part –II,

Section-3, subsection (ii) of Ministry of Environment & Forest dated 14.09.2006 &

subsequent amendments, the proposed project falls in 5 (f) Synthethic organic chemicals

& industry (dyes & dye intermediates; bulk drugs and intermediates excluding drug

formulations; sysnthethic rubbers; basic organic chemicals; other synthethic organic

chemicals and chemical intermediates of schedule of EIA Notification,2006 and

categorized under “A” Category as the industry is located outside the industrial estate of

“List of Projects or activities requiring prior Environmental Clearance”. As per the above

notification, proposed project will have to obtain environmental clearance from MoEF &

CC New Delhi.

Project Details:

Sr. No. Points Description

1. Title of the project M/s. Venkata Narayana Active Ingredients

Private Limited

(Formerly Nutra Specialties Private

Limited)

2 Land Acquired Existing Land :33.0 Acres

Existing Green belt :11 Acres (33% as per

Norms)

Existing Builtup Area :11.0 Acres

Road Area : 1.0 Acres

Open space area : 10 Acres

3. Cost of the Project 15 Crores

4 Proposed facilities Manufacture of Bulk drug and Intermediates

( Expansion of existing product capacities

and machinery) in the existing facility.

5 Production Capacity

Expansion of existing products from142.32

TPA to 500 TPA.

5


Existing over all production : 142.32 TPA

After Expansion over all production : 500

TPA

6 Water Requirement The existing and proposed fresh water

source is Bore Well.

Existig fresh water requirement : 173.80

KLD

S.No Description Quantity (KLD)

1. Process &

Washings

13.80

2. Industrial Cooling 100.0

3. Boiler feed 42.0

4. Gardening 10.0

5. Domestic 8.0

Total 173.8

After Expansion Fresh water

requirement: 298.09 KLD


1. Process &

Washings

29.09

2. Industrial Cooling 180.0

3. Boiler feed 68.0

4. Gardening 10.0

5. Domestic 11.0

Total 298.09

7 Waste Water Treatment Waste water generatedfrom the existing

facility is 67.03 KLD. The industry

adopeted Zero Liquid Discharge.


6


1. Process & Washings

14.23

2. Boiler Blow Down 11.8

3. Cooling Tower 35.0

4. Domestic 6.0

TOTAL 67.03

After the expansion the waste water

generation will be about:


1. Process & Washings

35.39

2. Boiler Blow Down 16.8

3. Cooling Tower 45.0

4. Domestic 9.0

TOTAL 106.19

Domestic waste water will be treated in

sewage treatment plant of 10 KLD

8 Solid & Hazardous Waste

Management and Disposal

Existing Solid Waste & Hazardous waste

Solid waste: Boiler Ash- 3.0 TPD

Hazardous waste:

Solid waste from process – 740.82 Kg/day

Waste oil - 120 lit/year

ETP Sludge – 10.32 Kg/day

Salts from Multiple Effect Evaporation -

135.48 Kg/Day

Carbon Waste -21.85 Kg/day

Solvent residue & Organic residue -218.7

Kg/day

Stripper distillate -238.9 Kg/day

Mixed Solvents -45 TPM

Container and container liners after

detoxification -30 Nos/ Month

7


After Expansion Solid Waste

&Harzardous Waste Details:

Solid Watse :

Boiler Ash: 5.0 TPD

Hazardous waste:

Solid waste :1457.83 Kg/day

Waste oil - 500 lit/year

ETP Sludge – 25.0 Kg/day

Salts from MEE system : 900 Kg/day

Carbon Waste -80.55Kg/day

Solvent residue & Organic residue :

3565.114 Kg/day

Stripper distillate : 450.0 Kg/day

Mixed Solvents : 90 TPM

Container and container liners after

detoxification : 60 Nos/ Month

9 Green Belt Around 11.0 acres land is for Green Belt

2.0 Introduction of the Project

2.1 Identification of Project & Project Proponent

Project Proponent: M/s. Venkata Narayana Active Ingredients Private Limited

( Formerly Nutra Specilaities Private Limited)

Regd Address: K.Varatharajan

Head-Technical Services

Sy.No:69 Chandrapadiya Village,

Vinjamur Mandal,

Nellore District-524228

2.2 Nature of Project

The industry proposes to expand their existing capacities of products from 142.32 TPA to

500 TPA within the existing premises with increase in machinery and change in process

technology thus resulting in modification of process. A new production block is

proposed within the existing premises which bifuricates API manufacturing and

Intermediate manufacturing which is at present happening in one block.

8

2.3 Need of Project

Due to huge market demand of the API or Bulk drug the industry proposes to expand

their existing products from 142.32 TPA to 500 TPA. Globally active pharmaceutical

ingredients (API) also know as bulk drug market is expanding due to an increase in the

incidence of actue and chronic disease. So the industry proposes to expand the production

capacity. The proposed products are having huge market value due to growing demand of

the products.

Cureently India is one of the world largest and most developed in the pharmaceutical

industry. The progress of the drug industry has not only rendered the country self

sufficient in National Health Care but also increase the foreign trade.

2.4 Employment generation

The industry has a storng team of R & D, Quality Assurance, Quality Control,

Production, Technical Services, Manufacturing, Packing, testing with Doctorates, Post

Doctorates, Graduates and Chemical Engineers . 70 members employment oppurtunities

will be given for expansion preferabally who are local villagers from economically

weaker section.

3.0 Project Description

3.1 Type of Project

As per EIA Notification dated 14 Sep 2006 this projects falls under 5(f) .The proposed

expansion is in the existing industry premises. The industry proposes to expand their

existing product capacities of the bulk drug intermediates with change in process

technology and increase in machinery.

3.2 Location

The proposed expansion project is located in the existing industry land Chandrapadiya

Village, Vinjamur Mandal, SPSR Nellore

Latitude : 14°45'53.97"N

Longitude : 79°35'33.55"E

9

Site Particulars

S. No Particulars Details

1. Nearest town / city Vinjamur – 7.53 kms

2. Water Bodies

Biraperu River at 2.22 km in North East

NakkaVagu – 6.17 km in South West

Water body near Gulapadu at -6.47 in North East

KothapalliVagu at 2.35 km in South East

3. Nearest Port Nil in 15 km radius

4. Archeologically

Important Places

Nil in 15 km radius

5.

National parks / Wildlife Sanctuaries/ Eco sensitive zones as per Wild Life Protection Act, 1972

Nil in 15 km radius

6. Reserved / Protected

Forests

RajavuluDubagunta RF at 0.48 Km

RajavuluPunugodu at 4.09 Km

Chintalapalem RF at 2.50 Km

Vinjamur RF at 4.20 Km

Abbasahedbupeta RF at 4.40 Km

7. Seismicity Zone III

8. Defense Installations Nil in 15 km radius

There are no archaeological,historical sites located nearby. The project site doesnot have any

adverse or negative impact on the environment, terrestrial or socioeconomic conditions. Google

map is attached below:

GOOGLE MAP OF 10 KM RADIUS

10

GOOGLE MAP OF 10 KM RADIUS.

11

TOPO SHEET OF 10 KM RADIUS

12

SITE PLAN

13

3.3 SIZE OR MAGNITUDE OF OPERATIONS.

LIST OF PRODUCTS AS PER EC EXPANSION VIDE ORDER NO: F.NO.J-

11011/1313/2007-IAII(I) DATED: 02.02.2009

S.No Products Capacity Kg/ Month

1 Solanesol 250

2 Ubequinone 2000

3 Tetrohydrocur cumin 80

4 Glucasomine 80

5 10-DAB-III 80

6 Thicochicoside 80

7 Tacrolimus 80

8 Digoxin 80

9 Hyoscine Butyl Bromide 80

10 Iron Sucrose 1000

11 Iron Sorbitol 1000

12 OlimesartanMedoxomil 500

13 Boswellic Acid 500

14 Capacitabine 100

15 Tioconozole 200

16 Ezitamibe 200

17 Sertraline HCl 500

18 Moxiflaxacin 500

19 Tetracine Hydrochloride 500

20 NebivilolHCl 200

21 Wafarine Sodium 500

22 Vitamin K2/4 100

23 Policosanol 500

24 Teprenone 500

14

LIST OF PRODUCTS WITH STARTING RAW MATERIAL AS PER THE

LATEST CFO ORDER VIDE ORDER

NO:APPCB/VJA/NLR/10725/HO/CFO/2018 DATED:14.12.2018

S.No. Product Starting Raw Material Product Capacity

Kg/day

1. Sitagliptin phosphate 2,4,5 tri flouro phenyl acetic acid 3.33

2. Levetriracatam (s)-2-amino butyramideHCl 166.67

3. Lacosamide D-Serine 16.67

4. Risperidone 3-(2-chloro ethyol)-2-methyl-6,7,8,9-

tetra hydro – 4H-pyrido-(1,2-a)-

pyrimidine-4-one-hydrochloride

4.0

5. Diacerine Aloe emodine 3.338

6. Vildagliptin L-proline 5.0

7. Policosanol Extracted crude 0.13

8. Warfarine sodium 4-hydroxyl cumarin 4.0

9. Tetracaine hydrochloride 4-amino benzoic acid 20.0

10. Olmisartanmedoxomil Imidazole ester 83.34

11. Boswellic acid Boswelliaserata gum 0.1

12. Moxifloxacin

hydrochloride

Gati Acid 3.33

13. Linagliptin Xanthan moiety 6.66

14. Voglibose Voglibose Crude 0.83

15. Teneligliptin 4-oxopyrrolidine carboxylic acid 0.33

16. Sevelamer Carbonate Allyamine 0.33

17. Pregabalin Ter-butyl-3-(hydroxyl methyl)-5-

methy hexanoate

0.33

18. Colistimide 2-methyl imidazole 0.33

19. Gabapantine Gabapentine tech 0.33

20. Methylcobalamin Cyanocobaltamin 0.16

21. L-MethylfolateCalsium Folic acid 0.33

22. Ferric Citrate Ferric chloride 0.15

23. Chlorozoxazone 4-chloro-2-aminophanol 0.15

15

24. Nitrofurantoin

Monohydrate

Urea 0.15

25. Cinacalcet

Hydrochloride

3-(3-Trifluoromethyl-phenyl)-

propionaldehdye

0.06

26. SucroferricOxyhydroxide Ferric chloride 0.06

27. Dimethyl Fumarate Fumaric acid 0.06

28. Atovaquone Intermediate-1 0.06

29. Droxidopa Intermediate-1 0.06

30. Allyl Isopropyl Acetyl

Urea

Dimethyl malonate 33.34

31. Fexofenadine HCl Fexofenadine HCl Crude 16.67

32. Loxoprofen 2-Phenyl propanoic acid

13.33

33. Loratadine Loratadine crude

8.33

34. Bepotastin Bepotastin crude

1.67

35. AzilsartanMedoxomil Benzo carboxylate

1.67

16

PRODUCTS AND THEIR QUANTITIES AFTER PROPOSED EXPANSION:

S.No. Product name Existing as per

CFO

Dated:14.12.2018

(kgs/day)

After Expansion

(Kgs/day)

1 Sitagliptin phosphate 3.33 66.67

2 Levetriracatam 166.67 466.67

3 Lacosamide 16.67 66.67

4 Risperidone 4.0 7.50

5 Diacerine 3.338 8.33

6 Vildagliptin 5.0 70.00

7 Policosanol 0.13 3.33

8 Warfarine sodium 4.0 20.00

9 Tetracaine hydrochloride 20.0 25.00

10 Olmisartanmedoxomil 83.34 110.00

11 Boswellic acid 0.1 3.33

12 Moxifloxacin hydrochloride 3.33 16.67

13 Lingaliptin 6.66 6.67

14 Voglibose 0.83 1.67

15 Teneligliptin 0.33 16.67

16 Sevelamer Carbonate 0.33 8.33

17 Pregabalin 0.33 8.33

18 Colistimide 0.33 8.33

19 Gabapantine 0.33 8.33

20 Methylcobalamin 0.16 3.33

21 L-MethylfolateCalsium 0.33 3.33

22 Ferric Citrate 0.15 3.33

23 Chlorozoxazone 0.15 8.33

24 Nitrofurantoin Monohydrate 0.15 8.33

25 Cinacalcet Hydrochloride 0.06 8.33

17

26 Sucroferric Oxyhydroxide 0.06 8.33

27 Dimethyl Fumarate 0.06 3.33

28 Atovaquone 0.06 3.33

29 Droxidopa 0.06 3.33

30 Allyl Isopropyl Acetyl Urea 33.34 166.67

31 Fexofenadine HCl 16.67 33.37

32 Loxoprofen 13.33 200.0

33 Loratadine 8.33 8.33

34 Bepotastin 1.67 8.33

35 AzilsartanMedoxomil 1.67 1.39

Total 395.29 kgs/day (or) 142.32 TPA

1393.89Kgs/day (or)

500 TPA

18

LIST OF RAW MATERIALS AND THEIR CAPACITIES AFTER PROPOSED

EXPANSION:

S.No. Product Starting Raw Material After

Expansion

Kg/day

1. Sitagliptin phosphate 2,4,5 tri flouro phenyl acetic acid 52.085

2. Levetriracatam (s)-2-amino butyramideHCl 466.67

3. Lacosamide D-Serine 47.621

4. Risperidone Rose 1 6.410

5. Diacerine Aloe emodine 6.576

6. Vildagliptin L-proline 30.434

7. Policosanol Extracted crude 24.975

8. Warfarine sodium 4-hydroxyl cumarin 9.83

9. Tetracaine hydrochloride 4-amino benzoic acid 13.157

10. Olmisartanmedoxomil DL-Tartaric acid 97.05

11. Boswellic acid Boswelliaserata gum 6.66

12. Moxifloxacin

hydrochloride

Gati Acid 13.336

13. Linagliptin Xanthan moiety 6.292

14. Voglibose Voglibose Crude 1.770

15. Teneligliptin 4-oxopyrrolidine carboxylic acid 5.244

16. Sevelamer Carbonate Allyamine 3.165

17. Pregabalin Ter-butyl-3-(hydroxyl methyl)-5-methy

hexanoate

13.015

18. Colistimide 2-methyl imidazole 4.165

19. Gabapantine Gabapentine tech 8.768

20. Methylcobalamin Cyanocobaltamin 3.996

21. L-MethylfolateCalsium Folic acid 3.885

22. Ferric Citrate Ferric chloride 3.297

23. Chlorozoxazone 4-chloro-2-aminophanol 5.206

19

24. Nitrofurantoin

Monohydrate

Urea 2.335

25. Cinacalcet

Hydrochloride

3-(3-Trifluoromethyl-phenyl)-propionaldehdye 6.941

26. SucroferricOxyhydroxide Ferric chloride 3.01

27. Dimethyl Fumarate Fumaric acid 2.973

28. Atovaquone Intermediate-1 1.665

29. Droxidopa Intermediate-1 5.994

30. Allyl Isopropyl Acetyl

Urea

Dimethyl malonate 166.67

31. Fexofenadine HCl Fexofenadine HCl Crude 35.3722

32. Loxoprofen 2-Phenyl propanoic acid 142.857

33. Loratadine Loratadine crude 8.5

34. Bepotastin Bepotastin crude 8.5

35. AzilsartanMedoxomil Benzo carboxylate 1.112

3.4 FUEL REQUIREMENT

Fuel required for the boiler is coal/ bio massand for DG sets the fuel is HSD.

3.5 MANPOWER REQUIREMENT

The plant will be continuous with 70 members employment for day to day operation for

expansion.

20

3.6 PROCESS FLOW CHARTS

PROCESS FLOW CHARTOF SITAGLIPTIN PHOSPHATE

SITAGLIPTIN PHOSPHATE STAGE: SGP1

2,4,5, Trifluro pheny lMDC

acitic acid DMF

Thionylchloride

Produced gas will send to scrubber

acid Meldrum MDC TEA

Water Separate the

Water layer to

waste water

Toget recovery

MDC

Ethyl acetate MSA

SIDE CHINE

Reflux the mass for

3 hrs

After reaction completion

After maintenance

Stir the mass for 3 hrs

at 0°C

Distill out the solvent

Crude

21

PROCESS FLOW CHART OF SITAGLIPTIN PHOSPHATE


Water Separate the Aq. layer to Waste water. Ethyl acetate

Wash with NaHCO3 Separate aq.layer

Solution to waste water

Wash with NaCl

solution

EA To get

recovery

Liq. Ammonia Methanol

Ammonium acetate

Crude

Stir the mass at reflux for 3 hrs

Cool the mass to RT

EA layer

Distill out EA

22



water

Reflux for 4 hrs

Centrifuse

Stage-I

23



Toluene

Acitic acid

Sodium borohydrate

Water Separate the

tolueme to

Tolueme get recovery

NaOH solution

Separate the

Extract with Aq.layer

MDC to waste water

Separate the

Wash with water Aq. Layer

waste water

MDC layer

Stage-I

Stir the mass for 1 hr at

0-5 °C

Reaction mass

Aq.layer adjust pH 10-11

Reaction mass

24



to get the

recovery MDC

R-Mandlic acid

IPA

Water

To get recovery

IPA

Distill out the MDC

Crude

Centrifuge

Stage-II

Stir for 1 hr at 9-10°C

25



NaOH solution MDC

Separate Aq.layer

to waste water

IPA

Phosphric acid

Water

Distill out MDC layer

Crude

Reflux the mass

Stage-II

Col the mass to 20°C

26



IPA recovery from

ML’S

Stir the mass for 12 hrs at

20°C

Centrifuse

SITAGLIPTIN PHOSPHATE

27

PROCESS FLOW CHART OF LEVETRIRACATAM

LEVETIRACETAM STAGE: LTA1

S-2-Amini butramideHcl MDC

Chlorobutyl chloride

TBAB KOH

To separate

solid waste

To separate the

Solid waste ,

Carbon,

Sodium sulphate.

MDC

recovery


at 0-5°C

Stir for 1 hr at RT

Filter the mass

Filter ML’S

Filter the mass for

Through hyflow bed


28

PROCESS FLOW CHART OF LEVETRIRACATAM

LEVETIRACETAM STAGE: LTA1

Ethyl acetate

EA recovery from

ML’S

Residue waste

BRIEF PROCESS DESCRIPTION OF LEVETIRACETAM

(S)-2-Amino butyramide react with 4-Chlorobutyl chloride in the presence of KOH and TBAB

catalyst and MDC media at 0°-5°C and compound isolate in ethyl acetate to give Levetiracetam

pure compound.

Centrifuse

Crude

LEVETIRACETAM

29

PROCESS FLOW CHART OF LACOSAMIDE

LACOSAMIDE STAGE: LAC1

D-Serine Di-tertiary butyl

Water dicarbonate

NaOH

NaOH Water

DMS

Separate the

water layer.


at RT


Cool the mass to 0-5°C

Extract the mass with MDC

30



Benzyl amine

Iso butyl chloroformate

N-Methyl morpholine MDC

Wash with water Separate the

Water layer

Wash with 1N.Hcl

Separate the

1N.Hcl layer to

waste water

Wash with 8% Separate the

sodium bi 8% Sodium

carbonate bicarbonate

layer to waste

Stir the mass for 2 hrs at

20 °C

MDC layer

Stir the mass for 2 hrs at RT

Take MDC layer

Take MDC layer

31



Wash with water Separate the

water layer to

waste water

Con .HCl

Charge water

30 % NaOH

Extract with MDC Separate the

Aq. layer to

waste water

Aqueous layer pH 10-12

MDC layer

Take MDC layer

Take MDC layer


Reaction mass

Reaction mass

Separate the

organic layer to

send for recovery

solvent

32



Acetic anhydride

Water Separate the

Aq. layer to

waste water

Separate the

Wash with water Aq. layer to

waste water

To get the

recovery

MDC layer

MDC layer


Reaction mass

Distill out the MDC

33



Ethyl acetate

EA recovery from

ML’S

Residue from

ML’S

BRIEF PROCESS DESCREPTION OF LACOSAMIDE

D-Serine react with Di-ter- butyl dicarbonate and Dimethyl sulphate in the presence of

Aq.sodium hydroxide, in MDC media at 25°C below and this react with Benzyl amine in the

presence of Isobutyl chloroformate and N-Methyl morpholine in MDC media at below 0°C then

this reacts with Con.HCl in the presence of MDC media at RT and these reacts with Acetic

anhydride in the presence of MDC media at 10 degrees below and isolate in ethyl acetate to get

pure Lacosamide.

Crude solid

Cool the mass to 0°C and stir for 1 hr

Centrifuge

LACOSAMIDE

34

PROCESS FLOW CHART OF RISPERIDONE

RISPERIDONE STAGE: RDN1

ROSE-I Acetonitrile

ROSE-II Pottasium carbonate

Potasium iodide

HCL To scrubber

Acetonitrile

recovery from

ML’S

Waste ML’S to

Incinerate

Reflux

Condensation

Cool to RT

Stir for 30 minutes

Centrifuge

Risperidone Crude

35

PROCESS FLOW CHART OF RISPERIDONE

RISPERIDONE STAGE: RDN2

Ethyl acetate Carbon

.

Ethyl acetate

recovery from

ML’S

Residue waste

BRIEF PROCESS DESCRIPTION OF RISPERIDONE

3-(2-Chloroethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido-(1,2-a)-pyrimidine-4-one

Hydrochloride react with 6-Fluoro-3-(4-piperidinyl)-1,2-benzisoxazol Hydrochloride in the

presence of Potassium carbonate and potassium iodine catalyst and Acetonitrile media to give

Risperidone crude this purified by ethyl acetate.

Stage-I

Reflux 1hr

Filter through Hyflow bed

Cool to 2°C and stir for 2 Hrs

Centrifuge

RISPERIDONE

36

PROCESS FLOW CHART OF DIACEREIN

DIACEREIN STAGE: DRN1

Acetic anhydride

Sulphuric acid

Chromic acid

Water

Aloe emodine

Stir the mass 2 hr at

80°

Cool the mass to

25°C


40-45°

Quench the mass in

to cold water

Centrifuge the mass

DIACEREIN

(CRUDE)

37

PROCESS FLOW CHART OF DIACERINE

DIACEREIN STAGE: DRN2

Dimethyl acetamide

From centrifuge mls

will get dimethyl

acetamide recover

BRIEF PROCESS DESCRIPTION OF DIACEREIN

STAGE-I:-

Aloe emodine react with Acetic anhydride in the presence of Sulphuric acid and acetic acid

media and chromic acid catalyst at below 85°C and compound isolate in water to get Diacerein

crude.

STAGE-II:-

Diacerein crude purified with Dimethyl acetamide at 80°C to get Pure Diacerein.

Diacerein (crude)


75-80°C

Cool the mass to

below 12°C and stir

for 1 hr

Centrifuge the mass

DIACEREIN

(PURE)

38

PROCESS FLOW CHART OF VILDAGLIPTIN

VILDAGLIPTIN STAGE: VDG1

L-Proline MDC

Oxalyl chloride DMF

Ammonia gas

Produced gas will

send to scrubber

Separate the

Water layer to

Waste water

Separate the

water layer to

waste water

To get recovery

MDC

Stir the mass for

3 hrs at RT

Centrifuge the mass

Wash with water and

Distill out the MDC

Charge Hexane and stir

for 2 hours at 0°C


Stage-I

39



Chloro acetyl

chloride

TEA

MDC

Separate aq.layer

To waste water

To get MDC

recovery

Methanol

Distill out the MDC

Stir the mass for 2 hr at RT

and centrifuge

Stage-I

Stir the mass for 4 hr at

0°C to 5°C

Wash the layer with

water

Stage-II

40



THF

Tri fluro acetic Acitic acid

anhydride

P2O5

Water Separate the

aq. layer to

Ethyl acetate Waste water

To get the THF

EArecovery

Methanol

Centrifuge the mass

Stage-II

Stir the mass for 4 hr

atreflux

Reaction mass

Distill the solvent

Crude

Stage-III

41



TEA

VDG Intermediate MDC

Wash water Separate water

To waste water

To get MDC

recovery

Methanol

Methanol

Recovery from

Mls

Centrifuge

Stir the mass for 4 hr at RT

Organic layer

Distill out solvent

Stage-III

VILDAGLIPTIN

Crude

42

Stage-III react with 3-aminotericycl decane-1-ol in the presence of Potassium carbonate and

Potassium iodide catalyst and in THF media at reflux and compound isolate in Methyl tert-

butyl ether and methyl ethyl ketone to get Vildagliptin pure compound.

BRIEF PROCESS DESCRIPTION OF VILDAGLIPTIN

STAGE-I:-

L-praline reacts with Chloro acetyl chloride in the presence of THF media at reflux condition

and compound isolate in Methyl tert-butyl ether to get stage-I solid.

STAGE-II:-

Stage-I react with DCC in the presence of MDC media at reflux condition and compound isolate

in methyl tert-butyl ether to get stage-II solid.

STAGE-III:-

Stage-II react with Trifluro acetic anhydride in the presence of THF media at reflux and with

ammonium bicarbonate , extractions with ethyl acetate and compound isolate in methyl tert-butyl

ether to get stage-III solid.

STAGE-IV:-

43

PROCESS FLOW CHART OF POLICOSANOL

Extracted crude

Methanol

Ethyl acetate, carbon

BRIEF PROCESS DESCRIPTION OF POLICOSANOL

Take the Extracted crude and extract with Methanol at reflux and cool the mass to 20°C and

filter the mass then charge ethyl estate and reflux the mass in carbon media then filter the mass

and cool the mass to get the Policosanol pharma compound.

Policosanol

44

PROCESS FLOW CHART OF WARFARIN SODIUM

Sodium acetate, Acetic acid

Toluene

Toluene

IPA, Water, Sodium carbonate

BRIEF PROCESS DESCRIPTION OF WARFARIN SODIUM

STAGE-I

4-hydroxycoumarin react with Benzalacetone in the presence of sodium acetate and acetic acid

catalyst and toluene media to give stage-I solid

STAGE-II

Stage-I solid react with sodium carbonate in the presence of water and IPA media to give

warfarin sodium

4-Hydroxycoumarin Benzalacetone

Stage-I solid

Warfarin sodium

45

PROCESS FLOW CHART OF TETRACAINE HYDROCHLORIDE

+

NaOH, Methanol , Water

N,N-Dimethyl amino ethyl chloride HCl

Na2CO3, Lia NH3,HCl,Acetone

Hexane,. Toluene

Toluenu MethanolicHCl

N-BUTYL BROMIDE

P-AMINO BENZOIC ACID

STAGE-I SOLID

STAGE-II SOLID

TETRACAINE HYDROCHLORIDE

46

STAGE-I

P-Amino benzoic acid react with n-butyl bromide in the presence of NaOH catalyst and water

media, after that purified by methanol at reflux to give stage-I solid

STAGE-II

Stage-I react with N,N-Dimethyl amino ethyl chloride hydrochloride in the presence of Na2CO3

and methanol and toluene media at reflux, compound extract with diluted HCl ,compound

isolated by mass Ph adjusted PH = 7 – 8 with Liq ammonia and extracted with hexane to give

stage-II solid

STAGE-III

Stage-II dissolved in toluene and compound isolated by adjusting mass PH with methanolicHCl

to give tetracaine hydrochloride pure compound.

47

PROCESS FLOW CHART OF OLMESARTAN MEDOXOMIL

HNO3, H2SO4, Ammonia

Toluene, HCl,water

SOCl2, Ethanol, HCl, Sodium nitrite

Na2CO3, water

Methyl magnesium chloride, NH4Cl, EA

Diisopropyl ether

OTBN, DDH, trityl tin chloride

NaN3, Trityl chloride TTBB K2CO3, Acetone, TBAB

Sodium nitrite, 1,4-dioxane

Acetoin IPA, KOH, Acetone

triposzene DMDO-CI K2CO3 / Na2CO3

Dimethyl aniline TBAB,KI

Sulfuryl chloride

MDC,CHCl3

EA, HCl, K2CO3

Water

DL-Tartaric acid

Stage-II

Butaraldehyde

Stage-III (Imidazole ester)

Stage-IV

Olmesartan medoxomil

Stage-V

Stage-I

48

BRIEF PROCESS DESCRIPTION OF OLMESARTAN MEDOXOMIL

Stage-I: DL-Tartaric acid reaction with Nitric acid and sulphiric acid at cooling condition then

reacting with Butaradehyde to give stage-I intermediate

Stage-II: Stage-I intermediate reacting with thionyl chloride in the presence of ethanol to give

stage-II intermediate

Stage-III: Stage-II intermediate react with methyl magnesium chloride in toluene media to give

intermediate -III

Stage-IV:

Imidazole ester (Intermediate-III) and TTBB is refluxed in acetone in presence of potassium

carbonate & tetra butyl ammonium bromide. Salts are removed by filtration & followed removal

of solvent at reduced pressure to give Intermediate – I

Stage-V:

Olmesartan-IV reacted with Potassium hydroxide in isopropyl alcohol after this reaction mass is

refluxed with potassium carbonate in acetone. Salts are removed by filtration & followed

removal of solvent at reduced pressure to give Stage-II intermediate.

Stage-VI:

Stage-V react with sulphuric acid in the presence of ethyl acetate media and compound isolate in

ethyl acetate by adjusting the mass PH and to give Olmesartan medoxomil.

49

PROCESS FLOW CHART OF MOXIFLOXACINE HYDROCHLORIDE

Boric acid, ZnCl2

Acetic anhydride, A C N

IPA, TEA, Nonane, HCl

Methanol, NaOH

Con.HCl, Carbon, Hyflow

BRIEF PROCESS DESCRIPTION OF MOXIFLOXACINE HYDROCHLORIDE

STAGE-I:-

Gatiacid react with Boric acid in the presence of Acetic anhydride and zinc chlrode at 100 –

120oC and react with Nonane in the presence of A C N and IPA at 0oC and compound isolating

by adjusting PH = 1-1.5 with Con.HCl to give Stage-I solid.

STAGE-II:-

Stage –I react with Sodium hydroxide at 50 -60oC in methanol media and compound isolate by

adjusting PH = 1- 1.2 with Con.HCl to give Mexico pure compound.

Gatiacid

Stage-I

Mexico ( Pure)

50

PROCESS FLOW CHART OF BOSWELLIC ACID

MIBK, NaOH

HCl

Acetic acid

Acetic anhydride

Cat-P

Methanol

HCl

Acetic acid

Acetic anhydride

Cat-P

BOSWELLIA SERATAGUM

STAGE-I SOLID

STAGE-II WET SOLID

STAGE-III SOLID

BOSWELLIC ACID

51

BRIEF PROCESS DESCRIPTION OF BOSWELLIC ACID

STAGE-I

Boswellia serrate gum extracted with MIBK at 70°C and isolated by NaOH and HCl and solid

separated by filtration to give stage-I solid.

STAGE-II

Stage-I compound is treated with Acetic acid and Acetic anhydride in the presence of Cat-P at

40°C and solid isolated by water to give stage-II wet solid

STAGE-III

Stage-II wet solid is treated with KOH and aq methanol at 75°C, and compound isolated by PH

adjustment with HCl in the presence of water to give stage-III solid.

STAGE-IV

Stage-III solid treated with Acetic acid and Acetic anhydride in the presence of Cat-P at 70°C

and compound isolated by PH adjustment with NaOH solution in the presence of water to give

Boswellic acid pure compound

52

PROCESS FLOW CHART OF LINAGLIPTIN

DMSO,K2CO3,Methanol, water,TBAB

DMF,K2CO3,Acetone.MIBK

IPA,NaOH,Acetic acid

tert-butyl piperidin-3-yl carbamate

TFA,MDC,K2CO3

Intermediate 2-(Chloromethyl)-4-

Methylquinazoline

Stage-1

LINAGLIPTIN

Stage-II

53

BRIEF PROCESS DESCRIPTION OF LINAGLIPTIN

STAGE-I:-

Intermediate react with 2-(chloromethyl)-4-methylquinazoline in the presence of NMP( N-

Methyl pyrroline) and sodium carbonate in acetone media at reflux condition to give stage-II

solid.

STAGE-II:-

Stage-II react with tert-butyl piperidin-3-yl carbamate in the presence of DMF and potassium

carbonate in acetone media at reflux condition to give stage-I

STAGE-III:-

Stage –II de protected in the presence of TFA ( Trifluro acetic acid) and sodium carbonate in

MDC media at reflus condition to give Linagliptin pure compound.

54

PROCESS FLOW CHART OF VOGLIBOSE

Methanol ,Hyflow

BRIEF PROCESS DESCRIPTION OF OGLIBOSE

Voglibose crude purifying by methanol at 50oC -55oC to give Voglibose pure compound.

VOGLIBOSE

(CRUDE)

VOGLIBOSE

(PURE)

55

PROCESS FLOW CHART OF TENELIGLIPTIN

+

MDC, Trifluoroaceticacid

NaHCO3, Piperazine Intermediate

1,3-thiazolidine

MDC, Piperidine

BRIEF MANUFACTURING PROCESS

Stage – I:

4-oxopyrrolidine carboxylic acid react with Piperazine Intermediate at RT in presence of

Trifluoroacetic acid and Sodium bi carbonate in MDC media to give Stage – III compound.

Stage – II :

Stage – III Reacts with 1,3-Thiazolidine in MDC media in presence of Piperidine at RT for 5 to 6

hours to give Teneligliptin.

4-oxopyrrolidine carboxylic

acid

Piperazine Intermediate

Phosphoric Acid

Teneligliptin

Stage - III

56

PROCESS FLOW CHART OF SEVELAMER CARBONATE

+

Lime solution, Water

40 degrees

Epichlorohydrin

Methanol

RT

BRIEF PROCESS DESCRIPTION OF SEVELAMER CARBONATE

STAGE-I:-

Allyamine react with Bicarbonate and lime solution in the presence of water at 40 degrees and

compound will isolate in water to give stage-I solid

STAGE-II:-

Stage-I react with Ephichlorihydrin in the presence of methanol at room temperature and will

give the Sevelamercorbonate complex solid.

Allyl amine H2CO3

Allylamine Carbonate

SEVELAMER

CARBONATE

57

PROCESS FLOW CHART OF PREGABALIN

+

TsCl,Pyridin

DMSO,MDC,EA

KOH,EA

H2,Pd/C, MDC

BRIEF PROCESS DESCRIPTION OF PREGABALIN

STAGE-I:-

Tert-butyl 3-(hydroxymethyl)-5-methylhexanoate react with Sodium azide in the presence of

TsCl and pyridine in the presence of DMSO media at 55 degrees temperature and separating the

salts in the presence of MDC and distilling the solvent completely then Ethyl acetate adding in to

the mass and compound isolating in methanol media at below 5 degrees to get stage-I solid.

STAGE-II:-

Stage-I reacting with hydrogen in the presence of Pd/C in MDC media at room temperature and

hydrolysis doing in the presence of KOH at room temperature then adding the Ethyl acetate and

compound isolating in the presence of Ethyl acetate at below 5 degrees to get Pregabalin.

NaN3 Tert-butyl 3-(hydroxyl

methyl)-5- methyl hexanoate

Tert-butyl 3-(hydroxyl


Tert-butyl 3-(hydroxyl


Intermediate-I

Pregabalin

58

PROCESS FLOW CHART OF COLESTIMIDE

2-Methyl imidazole

Epochlorohydrin,EDC

CAB, Acetone,water

BRIEF MANUFACTURING PROCESS OF COLESTIMIDE

2-Methyl imidazole react with Epichlorohydrin in the presence of 1,2 dichlorohydrine

media and cellulose acetate butyrate and sodium hydroxide media at 90 degrees and compound

isolating in acetone media to get pure colestimide .

Colestimide

59

PROCESS FLOW CHART OF GABAPENTINE

Methanol, Acetone

Ethyl acetate

BRIEF PROCESS DESCRIPTION OF GABAPENTINE

Gabapentine crude was purifying with Methanol and Acetone media at 60 degrees and

compound isolating in ethyl acetate media to get Gabapentine pure compound.

Gabapentine( pure)

Gabapentine (tech)

60

PROCESS FLOW CHART OF METHYLCOBALAMIN

+

Water,NaOH,Cobaltuschloride

Iso-butanol,Phenol,Chloroform

Trimethylsulfoxoniumiodide

Acetone, Hyflow

BRIEF PROCESS DESCRIPTION OF METHYLCOBALAMIN

Cyanocobalamin reactingwith sodium borohydride and trimethylsulfoxoniumiodide in the

presence of cobaltus chloride and Sodium hydroxide and phenol, chloroform media at 50 degrees

and compound isolating in the acetone and water media to get Methylcobalamin solid.

Cyanocobalamin Sodium borohydrate

Methylcobalamin

61

PROCESS FLOW CHART OF L-METHYLFOLATE CALSIUM

+

BHT,50%NaOH,HCl

Formaldehyde,Calsium chloride

Methanol,EA,Water

Hyflow

BRIEF PROCESS DESCRIPTION OF L-METHYLFOLATE CALSIUM

Folic acid reacting with sodium borohydrate and calcium chloride in the presence of BHT ,HCl

and NaOH in water mediate 40 degrees and compound isolating in methanol media to give L-

methylfolate calcium solid.

Folic acid Sodiuborohydrate

L-Methylfolatecalsium

62

PRODUCT NAME: FERRIC CITRATE Stage – I:

Ferric Chloride Anhydrous undergoes hydrolysis with Sodium carbonate solution (sodium

carbonate in Purified water) in presence of Purified water, washed the same with purified water

and isolated in to yield Ferric Citrate Stage – I [Ferric Hydroxide].

Stage – II:

Ferric Citrate Stage – I [Ferric Hydroxide] undergoes condensation with Citric Acid

Monohydrate in presence of Purified water, followed by charcoalisation with activated carbon

and Precipitation with Acetonitrile to yield Ferric Citrate, which finally undergoes purification in

Acetone to yield pure Ferric Citrate Stage – II [Ferric Citrate].

Process flow:

Ferric chloride Sodium carbonate Water

Ferric citrate stage-I Citric acid monohydrate Water Acetonitrile

Acetone

Ferric citrate stage-I

Reaction

Filtration

Precipitation

Packing

Reaction

Filtration

Precipitation

Ferric citrate salt

Drying

63

PRODUCT NAME: CHLORZOXAZONE:

Process Details:

Manufacture of Chlorzoxazone from 4-chloro-2-aminophenol involves one chemical

transformation step through carboxylation of 4-chloro-2-aminophenol in presence of

ethyl chloroformate with potassium carbonate and cyclized to get Chlorzoxazone

Into a stirred solution of Potassium carbonate, Ethyl acetate, 4-chloro-2-aminophenol

was added Ethylchloroformate and heated to 50-60°C for 2-5h cooled to room

temperature.

Slat filtered, organic layer pH adjusted and extracted with ethyl acetate, solvent

evaporated to get crude.

Crude was purified with ethyl acetate to yield Chlorzoxazone.

64

FLOW CHART FOR CHLORZOXAZONE:

Potassium carbonate

Ethyl acetate

4-chloro-2-amino phenol Ethylchloroformate

Ethyl acetate

Potassium salt of

Chlorzoxazone

1:1.Hydrochloric acid

Activated carbon

Potassium salt of Chlorzoxazone

Wet Chlorzoxazone

Reaction

Precipitation

Filtration

Purification

Drying

Reaction

Filtration

Distillation

Packing

65

PRODUCT NAME: NITROFURANTOIN MONOHYDRATE

In stage-01, Urea is dissolved in water, cooled to +5°C slowly added hydrazine hydrate solution

and stirred for 2h. Then Acetic acid was added and heated to reflux for 5h. Solution cooled to

room temperature, then added methyl chloro acetate and stirred for 5h at room temperature,

precipitated solid filtered and washed with acetone and dried under vacuum to get Nitrofurantoin

stage-01.

Product name Stage-II:

In stage-02, stage-01 is dissolved in Dimethylformamide, cooled to +5°C; sodium methoxide was

charged and stirred for 15min.Then 5-Nitro-2-furfuraldehyde diacetate was added and heated to

reflux for 5h. Solution cooled to room temperature, neutralised with Sulphuric acid, precipitated

solid filtered and washed with methanol and dried under vacuum to get Nitrofurantoin, which

was further purified with dimethylformamide and acetone to get pure Nitrofurantoin.


In stage-03, stage-02 is dissolved in purified water, cooled to +5°C; spray dried to get to get pure

Nitrofurantoin monohydrate.

66

PROCESS FLOW CHART OF NITROFURANTOIN MONOHYDRATE

Product name Stage-I:

Urea

Methyl chloro acetate

Hydrazine hydrate Acetone Acetic acid


Stage-01

5-Nitro-2-furfurald

ehyde diacetate

Sodium methoxide

Dimethylformamide

Sulphuric acid

Methanol

Purified water

Stage-01

Reaction

Precipitation

Filtration

Purification

Crystallizer

Reaction

Filtration

Crude Nitrofurantoin

Spray drying.

Packing

67

PRODUCT NAME: CINACALCET HYDROCHLORIDE

STAGE-I :

3-(3-Trifluoromethyl-phenyl)-propionaldehyde dissolved in methanol cooled to 5°C, added

Sodiumborohydride and stirred for10mins and then 1-Naphthalen-1-yl-ethylamine was

dissolved in methanol added slowly and brought to 25°C, stirred for 5h ,and washed with ethyl

acetate and concentrated to give the reductive aminated product, (1-Naphthalen-1-yl-ethyl)-[3-

(3-trifluoromethyl-phenyl)-propyl]-amine, as Cinacalcet stage-01.

STAGE-II :

In Stage-II, Cinacalcet stage-01 undergoes a salt formation with isopropanol in hydrochloric acid

in Tetrahydrofuran to give crude (1-Naphthalen-1-yl-ethyl)-[3-(3-trifluoromethyl-phenyl)-

propyl]-amine hydrochloride salt which was further purified with acetone to give Cinacalcet

hydrochloride.

68

PROCESS FLOW CHART OF CINACALCET HYDROCHLORIDE

Product name Stage-I:

3-(3-Trifluoromethyl-phenyl)

-propionaldehyde

Methanol 1-Naphthalen-1-yl-ethylamine Sodiumborohydride Ethyl acetate


Stage-01

Isopropanol hydrochloride

Tetrahydrofuran

Acetone

Stage-01

Reaction

Distillation

Filtration

Purification

Drying

Reaction

Filtration

Crude Cinacalcet

hydrochloride

Packing

69

PRODUCT NAME: SUCROFERRIC OXY HYDROXIDE

In Stage-I, the KSM, Ferric Chloride is reacted with Sodium Hydroxide to give Ferric

oxyhydroxide (Stage-I).

In Stage-II, Ferric Oxyhydroxide (Stage-I) is treated with sucrose and starch to give Sucro ferric

oxyhydroxide.

Process flow:

Ferric Chloride

Sodium Hydroxide

Water

Stage-01

Sucrose

Starch

Water

Stage-01

Sucroferric Oxy hydroxide

Reaction

Precipitation

Filtration

Packing

Purification

Drying

Reaction

Filtration

70

PRODUCT NAME: DIMETHYLFUMARE

KSM, Fumaric is reacted with methanol in the presence of methane sulfonic acid at 65-70°C give

dimethylfumare as a white crystalline solid after cooling.

Process flow:

Fumaric acid

Methanol

Methane sulfonic acid

Heat to 65-70°C

Methanol

Reaction

Filtration

Dimethylfumare

Purification

Drying

Packing

71

BRIEF PROCESS DESCRIPTION OF ATOVAQUONE

STAGE-I:-

Intermediate-I react with Intermediate-II in the presence of Silver nitrate and ammonium

persulphate catalyst in Acetonitrile media at 45 degrees to get stage-I solid.

STAGE-II:-

Stage-I solid was heated with KOH and water and compound isolating in methanol media at

60°C to give pure Atovaquone solid.

FLOW CHART OF ATOVAQUONE

+

AgNo3, A C N,

Hyflow

(NH4)2S2O3, Water

Intermediate-II

Stage-I

Intermediate-I

72

BRIEF PROCESS DESCRIPTION OF DROXYDOPA

STAGE-I:-

Intermediate-I react with Hydroxyl amine hydrochloride in the presence of sodium bicarbonate

base and Methanol media at 50 degrees and compound isolating in methanol to get stage-I solid.

STAGE-II:-

Stage-I solid was heated with dil. HCl in Isopropyl alcohol media at 60°C for some time. The

mass was cooled and filtered to give pure Droxydopa solid.

FLOW CHART OF DROXYDOPA

+

NaHCO3

Hyflow

Methanol, Water

HCl

Isopropyl alcohol

Water

Hydroxyl amine hydrochloride

Droxydopa

Stage-I

(2S,3R)-3-hydroxy-3-(3,4-

dihydroxyphenyl)-2-(1,3-

dioxoisoindolin-2-yl)propanoic acid

73

FLOW CHART OF ALLYL ISOPROPYL ACETYL UREA

Isopropyl bromide

Methanol, Sodium methoxide

Water

Allyl bromide , DMF

Sodium Hydride

Water

DMSO, NaBr

Water

DMF, Urea, NaH

Xylene, Methanol

Dimethyl Malonate

Stage-I

Stage-II

Stage-III

Allyl Isopropyl Acetyl Urea

74

BRIEF PROCESS DESCRIPTION OF ALLYL ISOPROPYL ACETYL UREA

STAGE-I:-

Di methyl malonate react with the Isopropyl bromide in the presence of Methanol and sodium

metal at room temperature and material isolate in MDC media to give Stage-I.

STAGE-II:-

Stage-I react with the Allyl bromide in the presence of Methanol and sodium metal at reflux

temperature and material isolate in MDC media to give Stage-I.

STAGE-II:-

Stage –II react with Sodium hydroxide at 50 -60oC in methanol media and Thionyl chloride and

Urea at 40 degrees then compound isolate in MDC to give Allyl Isopropyl Acetyl Urea pure

compound.

75

PROCESS FLOW CHART OF FEXOFENADINE HCl

Acetone ,Hyflow

BRIEF PROCESS DESCRIPTION OF FEXOFENADINE HCl

Fexofenadine crude purifying by Acetone at 50oC -55oC to give Fexofenadine

HCl pure compound.

FEXOFENIDINE HCl

(CRUDE)

FEXOFENIDINE HCl

(PURE)

76

PROCESS FLOW CHART OF LOXOPROFEN SODIUM

H2SO4, EA,water

Chlorosulphoni cacid, HBr,Hexane

Formaldehyde,EA,water,Na2CO3

Dimethyl adipate Methyl-2-oxocyclopentane carboxylate

NaH,Toluene,water,DMF

Con.HCl, Acetic acid

EA,Isopropyl acetate, water

. Potassium-2-ethyl hexanoate

NaOH,Ethanol

Isopropyl ether

Methanol

Stage-I

2-phenyl propanoic acid

Stage-II

Stage-III

Stage-IV

Loxoprofen Sodium

77

BRIEF PROCESS DESCRIPTION OF LOXOPROFEN SODIUM

STAGE-I:-

2-Phenyl propanoic acid reacting with methanol in the presence of sulphuric acid and ethy

acetate media at room temperature to give stage-I.

STAGE-II:-

Stage-I reacting with chloro sulphonic acid and HBr at 50 degrees in the presence of sodium

carbonate, formaldehyde and compound isolating in ethyl acetate to get stage-II.

STAGE-III:-

Stage-II reacting with methyl-2-oxocyclopentane carboxylate in the presence of Sodium hydride

in DMF media and toluene to give stage-III.

STAGE-IV:-

Stage-III react with acetic acid and Con.HCl in the presence of ethyl acetate and compound

isolate in Isopropyl acetate to give stage-IV.

STAGE-V :-

Stage -IV react with sodium hydroxide in the presence of ethanol and compound isolate in

isopropyl ether to give Loxoprofen sodium.

78

PROCESS FLOW CHART OF LORATADINE

Methanol, EA

DMF,Water

BRIEF PROCESS DESCRIPTION OF LORATADINE

STAGE-I:-

Loratadine purifying with methanol and ethyl acetate to give Loratadine pure compound

Loratadine crude

Loratadine pure

79

PROCESS FLOW CHART OF BEPOTASTIN

Methanol

DMF,Water

BRIEF PROCESS DESCRIPTION OF BEPOTASTIN

STAGE-I:-

Bepotastin crude purifying with methanol to give Bepotastin pure compound

bepotastin crude

Bepotastin pure

80

FLOW CHART OF AZILSARTAN MEDOXOMIL POTASSIUM

DMSO,NaHCO3

DMF,Water

1H-Imidazol-1-ylmethanone

DMSO

NaOH,HCl,Water

IPA,Formic acid, TEA

DMDO, DMA,p-TSCl

K2CO3,DMAP,MDC

Potassium-2-ethyl hexanoate

Acetone

Potassium-2-ethyl hexanone

Benzimidazole carboxylate

Intermediate

Hydoxyl amine

hedogensulphate

Stage-I

Stage-II

Stage-III

Stage-IV

AZILSARTAN

MEDOXOMIL POTASSIUM

81

BRIEF PROCESS DESCRIPTION OF AZILSARTAN MEDOXOMIL POTASSIUM

STAGE-I:-

1-((2-Cyanobiphenyl-4-yl)methyl)-2-ethoxy benzimidazole-7-carboxylate react with Hydroxyl

amine hydrogen sulphate in the presence of Sodium bi carbonate catalyst and DMSO media at

RT and compound isolate in water media to get stage-I.

STAGE-II:-

Stage-I react with 1H-imidazole-1-ylmethanone in the presence of DMSO media at hot condition

to give stage-II.

STAGE-III:-

Stage-II react with formic acid and sodium hydroxide in the presence of IPA media and TEA

catalyst at RT and compound isolate in water media by adjusting the mass PH with Hydrochloric

acid to give stage-III

STAGE-IV:-

Stage-III react with DMDO in the presence of p-Tolunesulphonic acid and potassium carbonate

catalyst and dimethyl amino pyridine media and compound isolate in MDC media at hot

condition to give stage-IV ( Azilsartanmedoxomil)

STAGE-V :-

Stage -IV react with potassium-2-ethyl hexanone in the presence of Acetone media at RT and to

give Azilsartanmedoxomil potassium pure compound

82

4.0 SITE SELECTION CRITERIA:

M/s. Venkata Narayana Active Ingredients Private Limited ( Formerly Nutra Specialties

Private Limited) is in operation in Chandrapadiya Village, Vinjamur Mandal, SPSR

Nellore since 2007 in the line of activity Bulk drug and its intermediates. As the proposed

project is expansion of existing product capacities is in the existing industry, no

alternative sites are envisaged.

The following points are considered for the expansion of the plant at existing premises

Proposed activity will be within the exitsing premises

Infrastructure facilities, like road, uninterrupted power industrial HT lines, water,

and manpower are available at the site.

Availability of water.

Ease of transport of both raw materials and products

Favorable climatic conditions

Industrial land

Land with sufficient green belt

5.0 UTILITIES:

5.1 Land:

The proposed expansion is in the existing industry premises only. The industry is having

a total of 33 Acres of land.

Total Land Area : 33.0 Acres

Existing Builtup Area : 11.0 Acres

Road Area : 1.0 Acre

Green Belt : 11.0 Acres

Open space : 10.0 Acres

5.2 Receipt of Rawmaterial:

All the rawmaterials will be transported to the facility through road only.

83

5.3 Water and Waste Water Details:

Fresh Water Requirement – Existing and Proposed

S.NO. Description Existing Quantity (KLD)

As per CFO

dated:14.12.2018

After Expansion Quantity

in KLD for 500 TPA

1. Process & Washings 13.80 29.09

2. Industrial Cooling 100.0 180.0

3. Boiler 42.0 68.0

3. Gardening 10.0 10.0

4. Domestic 8.0 11.0

Total 173.8 298.09

Note: Due to modernization of existing cooling towers drift losses will be less thus

resulting in reduction of fresh water requirement for cooling tower makeup.

Waste Water Generation – Existing and Proposed

S.NO. Description Existing quantity (KLD)

as per CFO

dated:14.12.2018

After Expansion Quantity in

KLD for 500 TPA

1. Process & Washings 14.23 35.39

2. Boiler Blow Down 11.8 16.8

3. Cooling Tower 35.0 45.0

4. Domestic 6.0 9.0

TOTAL 67.03 106.19

84

Treatment & Disposal – After Expansion

Source of effluent Mode of Disposal

Process effluents : HTDS – 35.39 KLD

Stripper (1 KL/hr-2

Nos.), MEE (3 KL/Hr),

MEE (1KL/Hr) as

standby, ATFD (500

L/Hr), ATFD (0.1

KL/Hour) as stand by.

Shall be stripped off for

organics recovery

Stripper condensate to

distillate for separation of

organic compounds

followed by disposal to

Cement Plants for co-

processing & distilled

effluents shall be

recycled.

Stripped effluents for

forced evaporation in

MEE followed by ATFD.

Condensate from MEE &

ATFD shall be recycled

after treatment in ETP

along with other LTDS

effluents.

ATFD salts to TSDF

LTDS Effluents: 61.8 KLD ETP of 160 KLD (ETP 1- 100

KLD and ETP 2- 60 KLD)

ETP 1 - 100 KLD

capacity consisting of

Collection tank cum

Equalization tank,

Flash mixer, Aeration tank,

Secondary settling tank,

Sand filter, UV purifier,

Sludge tank, Filter press,

RO Plant.

ETP 2 - 60 KLD consists of

Primary settling tank,

After treatment in ETP the

effluent will be sent to RO

Plant.

MEE condensate to ETP

followed by RO

RO permeate used for

greenbelt development

with in industry premises.

RO rejects to MEE

85

equalization tank, Aeration

tank,Secondary settling tank

Domestic : 9 KLD Sewage Treatment Plant of 10

KLD

After treatment in STP used for

green belt development.

5.4 DISPOSAL OF EFFLUENTS- ZERO LIQUID DISCHARGE

The industry has well equipped Effluent Treatment plant and also has provision for Zero

Liquid Discharge. The industry is achieving Zero Liquid Discharge and treating the

effluents to the board standards. Effluent Treatment Plant , its units and dimesnsions are

given below:

EXISTING TREATMENT SYSTEMS:

ETP 1 : 100 KLD

ETP 2 : 60 KLD

STP : 10 KLD

TREATMENT SCHEME:

Zero Liquid System included the following units:

Capacity of Stripper : 1 KL/Hour (2 Nos.)

Capacity of MEE : 4 KL/Hour ( 3 KL / Hr& 1 KL / Hr)

Capacity of ATFD : 0.1 KL/Hour

Capacity of ETP : 160 KLD (100 KLD+60 KLD)

Capacity of STP : 10 KLD

86

Different Raw Effluent will confirm to the following characteristics.

1. HTDS Effluent

pH : 7.0 – 11.0

Total Suspended Solids : 300-500 mg/l

Total Dissolved Solids : 10000-20000 mg/l

Biochemical Oxygen Demand : 5000-15000 mg/l

(3 days at 27oC )

Chemical Oxygen Demand : 25000-40000 mg/l

2. LTDS Effluent

pH : 7.0 – 11.0

Total Suspended Solids : 300-500 mg/l

Total Dissolved Solids : 2000-10000 mg/l

Biochemical Oxygen Demand : 500-1000 mg/l

(3 days at 27oC )

Chemical Oxygen Demand : 1500-2000 mg/l

6.0 Schematic Representative of feasibility drawing which give information

of EIA Purpose

Environmental Impact Assesment will be prepared as per ToR.

87

Pollution Prevention and Abatement Plan

S.NO. AREA OF CONCERN SOURCE POLLUTION CONTROL MEASURES

1. AIR POLLUTION Particulate Matter, SO2,

NO2& Hydrocarbons

Existing: 3 TPH Coal/ Bio Briquittes Boiler Proposed: The existing 3TPH boiler will be dismatlled and the industry is proposing to install 2 x 4 TPH Coal/ Bio Briquittes Boiler

Separate Multi Cyclone and common Bag filter

Closed system VOC Analyzer

Fugitive Emissions Vehicular emission

Roads are paved with road gravel. Fire water pumps and water

sprinklers are available 2. NOISE POLLUTION

Due to plant facilities Pumps / compressors

/Plant Machinery

Provision of silencers Sound-proofing the pump and compressor

33 % of total area Green belt development

Usage of modern technologies & machineries

Due to Power Back up Facility

DG Sets Existing: 1 x 500 KVA 1 x 725 KVA Proposed: 1 x1250 KVA

Acoustic enclosed ( Silent Generator)

Due to Transportation of materials & Construction Activities

Vehicles & Machinery

Provision of PPE to workers, Maintenance of machinery & vehicles

3. WATER Plant Facilities Process Water

cooling water, Boiler Blow down

ZLD ETP

Domestic Canteen, toilets etc Sewage Treament Plant 4. SOIL

Plant Facilities Hazardous waste from process, waste oil, carbon waste, MEE Salts etc

Shall be sent to TSDF or authorized agencies.

88

6.1 Solid Waste &Hazadous Waste Details

Solid & Hazardous Waste Details

S.No. Description Existing as per CFO

dated: 14.12.2018

After Expansion Mode of disposal

1. Solid waste from process 740.82

Kgs/day

1457.83

Kg/day

To TSDF for secured

land fill

2. ETP sludge 10.32

Kgs/day

25.0

Kg/Day

To TSDF for secured

land fill

3. Salts from MEE system 135.48

Kgs/day

900

Kg/day

To TSDF for secured

land fill

4. Carbon waste 21.85

Kgs/day

80.55

Kg/day

To TSDF for

incineration/Cement

industries for

processing

5. Solvent Residue &

Organic residues

218.7

Kgs/day

3565.11

Kg/day

To TSDF for

incineration/Cement

industries for

processing

6. Stripper waste 238.9

Kgs/day

450

Kg/day

To Cement industries

for co-processing

7. Mixed solvents 45

TPM

90

TPM

To authorized

recyclers/cement

plants

8. Spent Oil 120

LPA

500

LPA

Authorized recyclers

9. Container and container

lines of hazardous

chemicals (after

detoxification)

30

nos/month

60

nos/month

Authorized recyclers

10. Boiler Ash 3.0

TPD

5.0

TPD

Shall be disposed to

sold to Brick

Manufactures

89

6.2 Power Requirement / Source/

Power supply is obtained from APEPDCL and in case of power failure DG set of 1 x

500KVA and 1 x 725 KVA are installed.A new DG Set of 1 x 1250 KVA will be

installed for the proposed expansion.

7.0 SITE ANALYSIS:

7.1 Connectivity:

Plant is well connected by black top road. Nearest railway station is Venkateswarapalem

Railway Station 41.96 km away from plant.

7.2 Land Form, Land use & Land ownership

The proposed expansion project is within the existing industry premises . The industry

has own land of 33.0 Acres.

7.3 Climate:

The maximum temperature is 36 to 46 °C (97 to 115 °F) during summer and the

minimum temperature is 23 to 25 °C (73 to 77 °F) during winter. The rainfall ranges from

700 to 1,000 mm (28 to 39 in) through South West and North East Monsoons. Nellore is

subject both to droughts and to floods based on the seasons.

7.4 Social Infrastructure Avaialble:

As the proposed project is expansion of existing products, the industry is having well

equipped social infrastructure.

8.0 PLANNING BRIEF

8.1 Planning Concept

It is porposedto expand the existing product capacities within the existing plant premises.

8.2 Population projection

The closest village to the proposed site is Chandrapadiya at 0.39 Km. The proposed

facility does not envisage any displacement of population as it is within the existing

industry premises. Hence there is no impact on this account.

90

8.3 Land Use Planning

It is proposed to develop plant in 33.0 ac of which 11 acres is provided for green belt.

8.4 Assessment of infra structure Demand

Infrastructure required for the proposed facilities will be provided. The development shall

only lead to positive impact on infrastructure and services.

9.0 SOCIO- ECONOMIC ENVIRONMENT

The plant will provide direct and indirect employment and improve infrastructure

facilities and will provide the same in coming future as per the requirements.

Company will provide assistance to the nearby villagers for their development related

to education, hospital, postal, transportation, medical services etc.

The industry would help in promoting the activities related to environmental

awareness in the nearby villages.

Activities related to awareness for sanitation in schools & nearby villages,

Distribution of essentials in the schools and environment awareness camps will also

be organized.

9.1 Connectivity

All Road in this area are well constructed for heavy transportation only road will need to

construct for plant premises transportation. Nation Highway is 43.06 Km away from

project site. State High way Vinjamur – Atmakur is adjacent to the industry.

9.2 Drinking Water

The total man power after expansion in the plant will be 250 members on direct

employment. Their drinking water need met by using ground water only.The industry has

already obtained Ground Water Approval from the Board. Daily water need is about 11.0

KLD for domestic.

10.0 Rehabitation and Resettlement (R & R) Plan

The closest village to the proposed site is Chandrapadiya.The major occupations of

population are industrial labor activities.

There will be no displacement of local people as the proposed expansion project as it is

within the existing industry premises.

91

11.0 Project Scheduled and Project Cost.

The cost of the Project for the proposed expansion is Rs.15.0 Crores, which is scheduled

to be completed by target completion period of the project is within 12 months from the

date of EC from MOEF.

REQUEST TO PUBLIC HEARING FOR OUR PROPOSED EXPANSION:

The proposal is within existing industry premises. The proposed project is expansion of

production capacity within the existing industry for which we have already obtained EC

Order vide order no: J-11011/1313/2007-IA II (I) Dated: 02.02.2009 for which public

hearing was conducted on 26.09.2009 . Hence as it is only expansion within existing

industry premises we request you to kindly exempt us from Public Hearing.

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