06 Jun 2016 1723553975Y20Q3LXPreFeasibiltyReportMaithriDrugs PDF

Pre-Feasibility Report
(Proposed Expansion of APIs & Its Intermediate

Manufacturing Unit)
of
M/s. Maithri Drugs Pvt. Ltd.

Sy.No. 222,223 part, 224-226 & 205
Notified Industrial Area, Bonthapally,
Jinnaram (M), Medak District, Telangana
INDIA
Submitted to
SEIAA
‘Paryavarana Bhavan’, A3, Industrial Estate,
Sanathnagar, Hyderabad - 500018
Telangana State
Prepared by
KKB Envirocare Consultants Pvt. Ltd.,
Tarun Plaza, 1st Floor, 3-5-244,
NFC Main Road, Krishna Nagar Colony, Moula-Ali,
Hyderabad–500 040
NABET: Sl. No.102 NABET List as on 9th May 2016
June 2016
0|P a g e KKB ENVIROCARE CONSULTANTS PVT LTD., HYDERABAD, TS
for Proposed Expansion of APIs & Its Intermediates Manufacturing Unit of Maithri Drugs Pvt Ltd.,
Table of Contents
S.No Description Page No
1.0 Executive Summary 5

2.0 Introduction 8
2.1 Identification of the proposed project 8
Project Proponent
2.2 8
Brief Description of Nature of the Project
2.3 9
Need for the Project and its Importance to the Country and or
2.4 10
Region
Demand and Supply Gap
2.5 10
Imports vs. Indigenous production, Export Possibility,
2.6 10
Domestic/Export Markets
Employment generation (Direct & Indirect) due to the proposed
2.7 11
expansion project
Project description
3.0 11
Type of the project
3.1 11
Location
3.2 11
Alternate sites
3.3 13
Size or Magnitude of Operation
3.4 13
Project Description
3.5 15
Raw Materials
3.6 15
Resources Optimization / Recycling and Reuse
3.7 16
Availability of Water and Energy
3.8 16
3.9 Quantity of Wastes Generation and their Management / Disposal 16
Product wise Estimated Wastewater Quantity and its Pollution
3.9.1 16
Loads
Water requirement and Wastewater Generation and their
3.9.2 23
Management Disposal
Hazardous/ Solid Waste Generation, Handling and their Disposal
3.9.3 25
Schematic Flow Sheet for EIA Procedure
3.10 27
Site Analysis
4.0 27


Connectivity
4.1 27
Land Form, Land use and Land Ownership
4.2 28
Topography
4.3 28
Existing Land Use Pattern
4.4 28
Existing Infrastructure
4.5 28
Soil Classification
4.6 29
Climate Data from Secondary Sources
4.7 29
4.8 Social Infrastructure 29

Planning
5.0 29
Planning Concept
5.1 29
Population Projection
5.2 30
5.3 Land use Planning 30

Assessment of Infrastructure Demand
5.4 30
Amenities/Facilities
5.5 30
Proposed Infrastructure
6.0 31
Industrial Area
6.1 31
Residential Area
6.2 31
6.3 Greenbelt 31
Social Infrastructure
6.4 31
6.5 Connectivity 31
Drinking Water Management
6.6 31
Sewerage System
6.7 32
Industrial Waste Management
6.8 32
Process Emissions Management
6.8.1 32
Solvent management for effective recovery:
6.8.2 36


Emissions – Utilities
6.8.3 36
Noise Environment
6.8.4 38
Hazardous/ Solid Waste Management
6.9 38
Power Requirement & Supply / Source
6.10 38
Rehabilitation and Resettlement (R&R) Plan
7.0 39
Project Schedule & Cost Estimates
8.0 39
Time Schedule for the Project Construction
8.1 39
Estimated Project Cost
8.2 39
Analysis of proposal (Final Recommendations)
9.0 39
Budgetary allocation for Pollution Control Measures
9.1 40
Tables
Salient features of the proposed project
1 6
Land Use & break up details
2 8
Existing products with its capacity
3 13
Proposed Products with its Capacity
4 14
Product wise Pollution Load
5 19
6 Existing Water requirement and wastewater generation 23
7 Proposed Water balance and Segregation 24
8 Effluent Quantity and Treatment Flow for as per segregation 25
Existing Hazardous/SW Generation, Handling & Disposal details
9 26
Proposed Hazardous/SW Generation, Handling & Disposal details
10 26
Land Use Pattern of the Project Area
11 28
Proposed Process Emissions-Product wise
12 33
Maximum Quantity of Process Emissions for Proposed Products
13 35
Stack Emission Details
14 37
Budgetary allocation for Pollution Control Measures
15 41
Figures
Location of the proposed project
1 12

Annexures
I EC order copy dated 11-09-2006
II Certified Compliance Report from MoEF&CC regional office
III CFO dated 18-01-2010
IV CFO dated 13-5-2011
V RoC (Certificate of Incorporation) copy
VI CFE – CPM dated 15-3-2016
VII ToR copy from MoEF
VIII G.O.Ms.No.120 dated 22-10-2013 issued by Govt. of A.P. – Declaring
Industrial Area
IX Process description & flowchart
X Plant Layout
XI List of Hazardous Chemicals (Raw Materials)
XII List of Other Raw materials
XIII ETP schematic flow diagram
XIV Schematic flow sheet for EIA procedure
XV Google map showing Longitude and Latitude of Project location
XVI Topographical map with 10 km buffer
XVII Soil analysis report
XVIII Groundwater quality analysis report

1.0 Executive Summary
The proposed expansion industry was established during 1988 in the name of M/s. Bell
Remedies Limited to produce Sulfamethoxazole (10 TPM) as per No Objection
Certificate issued by A.P Pollution Control Board vide Lr.No.190/PCB/446/88-1139
dated 21.06.1988 and obtained Consent Order vide letter No. 1611/PCB/W/89/561
dated 10-08-1989. During the year 1994, the industry entered into the Agreement of
sale and was renamed as M/s. Bajaj Organics Pvt. Ltd., and obtained the CFE of the
Board vide order No. NI- 42/PCB/RO-SRD/94-1013 dated 24-10-1994 for manufacturing
Sulfamethoxazole (10TPM) and Ibuprofen (15 TPM). During 1994 the Board has further
issued 2nd NOC (vide Lr. No. NI-2/PCB/RO-SRD/95-445 dated 9-8-1995) for
manufacturing both Sulfamethoxazole and Ibuprofen. However, the industry could not
operate the plant due to various technical and financial constraints and went sick.
During the year 2005, the official liquidator of High Court of Andhra Pradesh, the unit
was released by the Court in favour of M/s. Bajaj Organics Pvt. Limited. Accordingly,
application submitted in accordance with MoEF Notification No.J-21011/8/98-IA.II (I)
dated 14th May 2002 for expost facto environmental clearance. The Ministry of
Environment and Forests has issued the ex-post facto Environmental Clearance to the
industry vide letter No. J-11011/295/2006-IA II (I) dated 11-09-2006 (Annexure I) & its
certified copy of the compliance report approved from MoEF&CC Regional Office dated
17-5-2016 (Annexure-II). Industry has obtained permission to manufacture
Sulfamethoxazole with production capacity of 10 TPM from the State Pollution Control
Board vide Consent Order No. APPCB/PTN/PTN/ 1611/CFO/2010-2296 Dated 18-01-
2010 (Annexure-III). Further renewal of consent & authorization was issued for
manufacturing of Sulfamethoxazole with production capacity of 10 TPM on regular basis
vide Consent Order No. APPCB/PTN/PTN/ 1611/HO/CFO/2011-543 dated 13-05-
2011(Annexure-IV).
M/s. Maithri Drugs Pvt. Ltd., incorporated in Feb 2013 (vide ref enclosed certificate of
incorporation as (Annexure V) and procured the assets of M/s Bajaj Organics Pvt. Ltd
in June 2013 and obtained the Consent for Establishment (CFE) (Change of product
mix) in the name of Maithri Drugs Pvt.Ltd from SPCB (Vide ref of Order No.
03/TSPCB/CFE/RO—RCP-II/HO/2016/2999; Dated 16.03.2016) (Annexure-VI). with a
total production capacity: 120 TPA (10 TPM) (from 18 products i.e., any 1 product at a
time on campaign basis).
Industry submitted form 1 application to MoEF&CC, Delhi and obtain TOR for expansion
vide dated F.No. J-11011/39/2014-IA II(I) dated 28-11-2014. (Annexure-VII) and
completed base line studies from Oct’15 to Dec’15 considering the formation of SEIAA
in Telangana and proposing to change in proposal for expansion. We are submitting

form 1 application to SEIAA for issue of TOR considering its baseline period for Oct’15
to Dec’15. The salient features of the proposed project are given below Table 1.
Table 1: Salient features of the proposed project
S.No Parameter Description

I Project Details
a Proposed & Existing Proposed: 540 TPA with R&D support facility (15
Products with capacity Products at a time out of 59)
Existing : 120 TPA (1 product out of 15 products)
b Category of Project as The proposed expansion project will fall under 5 (f)
per EIA Notification & Category “B”
Amendments (Based on G.O.Ms.No.120 dated 22-10-2013 issued
by Govt. of A.P. – Declaring Industrial Area) is
enclosed as (Annexure VIII).
c Project Location Sy.No. 222,223 part, 224-226 & 205, Notified
& industrial area, Bonthapally, Jinnaram (M), Medak
Lat/Longs District of Telangana.
GPS Coordinates (Center of the project)
Latitude 170 40’ 4.70” N
Longitude 780 22’ 48.44” E
d Topographical map No E44m/5 (56k/5), E44m/6(56k/6) Source: SOI
e Elevation (msl) 625 Meters
f Project Cost Total estimated cost of the project : Rs.110 Crore
(Rs.in Crore) towards purchase of land, building, plant & machinery
(Rs. 12 Crore existing & Rs. 98 Crore proposed
investment).
g Proposed Rs 11 Crore (including existing Rs. 1.43 Crore)
EMP Capital Cost & Rs. 9.58 Crore per annum.
EMP Recurring Cost
II Resources
a Water Requirement & Total water: 632.5 KLD
source of water (Fresh water :457.5 KLD & Recycle water 175 KLD)
Source : Groundwater through outside Tankers
b Power requirement & 5000 KVA Source: TSSPDCL (Telangana State
source Southern Power Distribution Company Limited).
c Utilities Boiler : 10 TPH; 5 TPH & 3 TPH Coal fired boilers
& 2 Lakh K.cal/hr coal fired TFH.
Existing: 1 TPH Coal fired (proposed to dismantle)
Coal: 74 TPD

D.G sets :
Proposed: DG sets with 1010 KVA x 3 No 650 KVA
& 380 KVA.
Existing: 125 KVA DG Set will be dismantled.
Fuel : 812 Lit/hr
d Manpower 800 Members (Direct: 500 & Indirect 300 nos)
requirement
III Other Details from the proposed project
a Nearest Railway Secunderabad : 29 Km
Station/Airport Airport :Rajiv Gandhi IAP: 47 Km
b Nearest Highway SH 6 – 0.7 Km
c Nearest Town/City Hyderabad and ORR of Hyderabad : 9 Km
Jinnaram 5.6 Km
d Nearest Habitation Shapurnagar 0.9 Km from the industry
Reserved Forests Narsapur R.F (Dense Mixed Jungle) >2.5 km (W)
Nawabpet R.F (Fairly Dense Scrub) >9 km (NE)
Kanukunta R.F (Dense Scrub) >8 km (NE)
Wailal RF (Dense Mixed Jungle) >6 km (S)
Pottagadda RF (Dense Mixed Jungle) > 7.5 km (SW)
Kazipally RF (Dense Scrub) > 8 km (S)
Dundigal RF (Dense scrub) > 8 km (S)
f Water bodies (surface) No water bodies less than 0.5 km
Gummadidala erra cheruvu - 2.4 km (NNW)
Pond near Kattalindagudem - 1.2km (W)
Ran cheruvu - 2.6 km (SW)
g Defence installation Dundigal air force station at 0.5 Km (NE-S)
IV Wastewater Total proposed wastewater will be around 199 KLD,
generation which will be segregated into HTDS/HCOD and
& disposal LTDS/LCOD and will be send to the ETP- ZLD.
V Solid Waste Solid waste mainly segregated into process
Managemnent & organic residues, inorganic salts and spent
disposal carbon. These wastes are hazardous in nature as
they emanate from the chemical reactions or un-
reacted chemical wastes.
Organic residues & Spent carbon will be disposed
of to Cement plants as recommended by CPCB
for use as alternate fuels either in the solid or
liquid form.
Inorganic salts are to be sent for landfill at HWMP
– TSDF.

2.0 Introduction
2.1 Identification of the Proposed Project
M/s. Maithri Drugs Pvt. Ltd. proposes expansion of APIs and its Intermediates
manufacturing facility in the existing facility at Sy.No. 222,223 part 224-226 & 205
(Notified Industrial Area) Bonthapally, Jinnaram (M), Medak District of Telangana State.
The proposed expansion of APIs and its Intermediates manufacturing unit is

proposed in the existing facility of 3.1 Ha (31,000 sq.m) and with additional land of 2.3
Ha (23,000 sq.m) totaling 5.4 Ha (54,000 sq.m). The land use pattern of the project is
presented. The land use & land breakup for the proposed and existing are given in
below Tables 2.
Table 2: Land Use & break up details
Existing Proposed Total
S.No Description Area
Area (Ha) Area (Ha) %
(Ha)
1. Built-up area 1.45 27
2. Roads 1.43 26
3. Open & vacant area 0.63 12
4. Greenbelt 1.89 35
Total 3.1 2.30 5.4 100
2.2 Project Proponent
As the proposed industry is being established by the technocrats, who have been
successfully operating similar units around Hyderabad become a Growing Group in
Pharmaceuticals. MSN Group is envisaged that the industry would be operated in a
clean and safe manner and would remain as a Model example in protection of
Environment by adopting the policy of sustainable development.
MSN Group is one of the fastest growing manufacturers of Active Pharmaceutical

Ingredients (APIs) and finished dosages in India. Established in the year 2003, MSN
Group comprises of four API manufacturing plants, one finished dosage facility and a
dedicated Technology development center. MSN Group management comprises of top
notch professionals, with extensive experience in synthetic chemistry, process
engineering, quality, IT, SCM, marketing, regulatory requirements and environmental
safety and a proven track record in pharmaceutical industry. Thriving on the platform of
innovation and excellence, it has developed and grown into a successful and profitable
enterprise with a portfolio covering all the major therapeutic range. The plants of MSN
group are ISO 9001-2008 certified, WHO: GMP, EU: GMP and USFDA approved. The

manufacturing units are designed as per WHO- GMP standards and sustaining to the
principles of Quality, Safety and sound Environment.
The proposed project is APIs & its Intermediates manufacturing facility. The
manufacturing process of APIs consists of chemical synthesis and multiple stage of
processing involving different types of chemical reactions. These drugs are mainly used
for human Medication after Formulation activity to be used for various diseases.
In this connection, the project proponent is applying Form-I along with draft Terms of
Reference (TOR) for obtaining TOR for the preparation of EIA, in line with issue of
Environmental Clearance. Hence, a technical pre-feasibility report highlighting the
proposed APIs and its intermediates including various operations and waste generation
cum mitigation measures has been prepared & submitted to the State Environmental
Appraisal Committee (SEAC) along with Form 1 & Draft TOR for approval & issue TOR.
2.3 Brief Description of Nature of the Project
The project proponent proposed to expand the existing manufacturing unit. The
products manufactured are used in API formulation industry, which are used by human
beings in the normal life.
The manufacturing process of API’s consists of chemical synthesis extending to

maximum of ten stages of processing involving different type of chemical reactions. The
entire process involves various technical, skilled and unskilled persons with due care to
meet various standards prescribed by authorities. The final products are tested by
sophisticated quality equipment before approval for further processing by API
formulation companies.
The technology for manufacturing the listed products under the proposed expansion
were available with in-house R&D & private consultants. Industry will implement only the
proven technologies in the R&D Department for the cost effective & environment
friendly practices.

2.4 Need for the Project and its Importance to the Country and or Region
The Indian pharmaceutical industry valued at $16 billion has portrayed tremendous
progress with reference to infrastructure development, technology base creation and a
wide range of production. The pharmaceutical industry produces API belonging to major
therapy groups. India ranks 4th worldwide accounting for 8 per cent of the world's
production (in terms of volume) and 13th in terms of value, the Indian pharmaceutical
industry has the potential to achieve over Rs.2, 00,000 Crore in formulations and API
production. The industries now produces API belonging to all major therapeutic groups
requiring complicated manufacturing process and has also developed Good
Manufacturing Practices (GMP) facilities for the production of different dosage forms.
The Pharma industry exports drugs and pharmaceuticals worth over $ 4.5 billion. It
ranks 17th in terms of export value of bulk activities and dosage. Indian exports cover
more than 200 countries including the highly regulated markets of USA, Europe, Japan
and Australia.
At a growth rate of 7 per cent per year, the pharmaceutical industry in India is well set
for rapid expansion. As a result of the expansion, the Indian pharmaceutical and
healthcare market is undergoing a spurt of growth in its coverage, services, and
spending in the public and private sectors.
2.5 Demand and Supply Gap
The products manufacture by the proponent has a great demand in Japan, China,
France, Germany, Belgium, South Africa, USA, Canada, Brazil, Guatemala, Argentina,
& Mexico etc. In addition, the products are also has great demand in domestic market
which are majorly consumed by Dr. Reddy labs, NATCO, Mylan etc. It is reported that
there is an increase in the consumption of these products by about 5-6% every year.
The increase in imports directly indicates the gap in the demand and supply of the
products in the domestic markets.
2.6 Imports vs. Indigenous production, Export Possibility, Domestic/Export

Markets
At present, the China is dominating the API market all over the world. The India was
importing all major intermediate chemicals required for manufacturing lifesaving drugs
i.e., Anti-Cancer Drugs, Anti-ulcer, Antidepressant, Antifungal, Antibacterial, etc. Most of
our imports are from Chinese companies and thus we are losing our valuable foreign
reserves to China. As mentioned above, the imports have gone up from Rs.4000 in
2005 to about Rs.10000.
10 | P a g e KKB ENVIROCARE CONSULTANTS PVT LTD., HYDERABAD, TS

2.7 Employment generation (Direct & Indirect) due to the proposed expansion
project
Employment generation will be around 800 members (500 direct & 300 direct) by the
proposed expansion project including the existing facility.
3.0 Project description

3.1 Type of the project
M/s Maithri Drugs Pvt Ltd proposed to expand its API and its intermediates
manufacturing facility. As per the EIA notification dated 14th September, 2006 and
amendments thereof. The proposed expansion project will fall under 5 (f) Category “B”
(Based on GO MS. No 120 Dated 22.10.2013 issued by Government of AP – Declaring
industrial area) and it was enclosed as (Annexure VIII).
3.2 Location
The proposed project is being located at Sy.No. 222,223 part, 224-226 & 205 (Notified
Industrial Area), Bonthapally, Jinnaram (M), Medak District of Telangana. The details of
the proposed project location and lay out of the proposed expansion including the
existing are showed in Figure 1.

Figure 1. Location of the proposed project

3.3 Alternate sites
The proposed project is in the existing and additional plant area at Notified Industrial
area, Bonthapally of Medak District, Telangana. Hence No alternate site has been
considered for the proposed project. The environmental considerations of the proposed
project site –
The proposed project is located in the notified industrial area.

There are no rare or endangered or endemic or threatened (REET) species of
animals or birds.
>900 m away from human habitation and > 1200 m away from water sources.
No National Park or Wild life Sanctuary or Eco sensitive within 10 km radius from
the proposed project.
The expansion site is within the industry and extended area,
Proposed expansion project is surrounded by industries.
Exist Transportation and Communication network
3.4 Size or Magnitude of Operation
Proposed: 540 TPA (any 15 products at a time out of 59 products) with R&D (Table 4)
Existing: 120 TPA (any 1 product out of 15 product) as mentioned in Table 3.
Table 3: Existing products with its capacity
Sl. Product name Capacity Capacity

No. (kg/day) (TPA)
1 Ceterizine Di hydro chloride 333.33 120
2 Aripiprazole 35 12.6
3 Atorvastatin Calcium 150 54
4 Dapoxetine Hydrochloride 100 36
5 Efinaconazole 10 3.6
6 Ibudilast 50 18
7 Mesalamine 100 36
8 Mirtazapine 50 18
9 Pregabalin 200 72
10 Sumatriptan Succinate 50 18
11 Telmisartan 100 36
12 Tigecycline 10 3.6
13 Valsartan 100 36
14 Voriconazole 20 7.2
15 Zonisamide 100 36
Total Products Capacity on worst combination (1 product at a time) 333.33 120

Table 4: Proposed Products with its Capacity
Sl. Product name Capacity Capacity

No. (kg/day) (TPA)
1 Ceterizine Di hydro chloride 333.33 120
2 Aripiprazole 35 12.6
3 Atorvastatin Calcium 150 54
4 Dapoxetine Hydrochloride 100 36
5 Efinaconazole 10 3.6
6 Ibudilast 50 18
7 Mesalamine 100 36
8 Mirtazapine 50 18
9 Pregabalin 200 72
10 Sumatriptan Succinate 50 18
11 Telmisartan 100 36
12 Tigecycline 10 3.6
13 Valsartan 100 36
14 Voriconazole 20 7.2
15 Zonisamide 100 36
16 Lomitapide 6 2.16
17 Ospemifene 10 3.6
18 Lumacaftor 6 2.16
19 Eluxadoline 6 2.16
20 Gemifloxacin mesylate 48 17.28
21 Sitagliptin Hydrochloride 48 17.28
22 Perindopril Erbumine 2.4 0.864
23 Cangrelor 2.4 0.864
24 Cilomilast 2.4 0.864
25 Sitafloxacin 2.4 0.864
26 Formoterol Fumarate 1.8 0.648
27 Clevidipine Butyrate 6 2.16
28 Rasagiline Mesylate 6 2.16
29 Landiolol 6 2.16
30 Zolmitriptan 6 2.16
31 Udenafil 6 2.16
32 Argatroban 6 2.16
33 Balofloxacin 6 2.16
34 Beraprost 6 2.16
35 Pazufloxacin 6 2.16
36 Talipexole 6 2.16
37 Almotriptan 6 2.16
38 Rizatriptan Benzoate 6 2.16
39 Canagliflozin 25 9
40 Emphagliflozin 25 9
41 Cefmetazole 12 4.32

42 Imipenem 12 4.32
43 Iloprost 12 4.32
44 Cefixime 12 4.32
45 Safinamide 21 7.56
46 Selegiline Hydrochloride 24 8.64
47 Brivaracetam 21 7.56
48 Asenapine Maleate 21 7.56
49 Ramipril 9 3.24
50 Zileuton 21 7.56
51 Vildagliptan 21 7.56
52 Temafloxacin Hydrochloride 21 7.56
53 Trovafloxacin 21 7.56
54 Palonosetron Hydrochloride 6 2.16
55 Salmeterol Xinafoate 6 2.16
56 Trandolapril 6 2.16
57 Ecabapide 6 2.16
58 Zafirlukast 9 3.24
59 Darifenacin Hydrobromide 9 3.24
Total (15 Products at a time out of 59 products) 536.16 TPA
R & D Activity 3.84 TPA
Total 540 TPA
3.5 Project Description
The manufacturing process of API & its intermediates consisting of chemical synthesis
extending to maximum of ten stages and process description & flowchart is enclosed as
(Annexure IX) stages of processing involving different types of chemical reactions.
These drugs are mainly used for human Medication after Formulation activity for various
diseases. Technology for manufacturing the proposed products is available from in-
house R&D & private consultants. Industry will implement the proven technologies in
R&D Department for the cost effective & environment friendly practices. The plant
layout showing all components of the proposed project as (Annexure X).
3.6 Raw Materials
The API manufacturing involves the use of various chemicals and organic solvents to
extract a product from the reaction mixture. The chemicals and organic solvents
required for the process are mostly bought from the local (indigenous) markets. Some of
the raw materials based on the requirement will be imported from the various countries.
The consumption of coal will be around 74 TPD for the proposed 10, 5, 3 TPH Coal
fired boiler &2 Lakh K.cal/hr coal fired TFH and 1TPH capacity of coal fired boiler is
being proposed to dismantled. The total power requirement of the proposed plant is
5000 KVA. About 740 lit/hr diesel will be used as a fuel for proposed 4060 KVA DG Set

(1010KVA x 3No; 650 KVA & 380 KVA and the existing 125 KVA DG Set will be
dismantled. The Mode of transportation of all raw materials and finished products from
the project site to the local markets is by road. If exported it will be transported by road /
rail / sea / air. The hazard chemicals and other raw materials to be required for the
manufacturing of proposed products are presented as (Annexure XI & XII).
3.7 Resources Optimization / Recycling and Reuse
R&D facility in the unit is taking all efforts to recycle the wastes / reuse wherever
possible. However, R&D is a continuous process, where improvements in the processes
adopted by the industry, waste minimization etc. will be worked out as the project
progresses. Following are some of the recycle options proposed by the industry.
 Industry is proposing for Zero liquid discharge plant to reuse all treated effluents as
makeup water for utilities like Cooling Tower. This will reduce the fresh water
consumption.
 Industry is proposing dedicated reactors for few products there by reducing the
reactor washings.
 All solvents are recovered to the extent possible and reused in the process.
 Organic residue and spent carbon will be sent to Authorized Cement industries to
burn in Cement Kiln as an alternate fuel.
 Boiler ash will be sent to Cement Brick manufacturing units.
 Waste / Used oil will be sent to Authorized Waste / Used oil Reprocessing units.
 Container & container liners of hazardous chemicals, Polythene / HDPE Bags,
broken plastic drums shall be disposed of to outside agencies after complete
detoxification.
 Spent catalyst will be sent back to supplies
 Waste Lead acid batteries will be sent back to suppliers on buy back basis.
 Optimum utilization of solar energy.
Recycling and reuse of solvents generated during the process will also be planned
properly thereby implementing the clean manufacturing techniques.
3.8 Availability of Water and Energy
The fresh water requirement will be around 457.5 KLD which will be met from outside
water tankers. The total power requirement will be 5000KVA and will be met from
TSSPDCL. Diesel will be procured from the distribution sources closer to the project.
3.9 Quantity of Wastes Generation and their Management / Disposal
3.9.1 Product wise Estimated Wastewater Quantity and its Pollution Loads
The estimated product wise Pollution load has been tabulated in Table 5.

Table 5.Product wise Pollution Load
EFFLUENT DETAILS SOLID WASTE Emissions

PRODUCTION
Practical
Total
Water
Water in Organics in Org.res./ Inorganics + Spent Total Solvent
Input Per Total Total Process
Effluent Effluent TDS COD Semi solid EVA.Salts Carbon S.W. Loss
S.No Product Day Effluent Effluent
Per Per Day
Tons / Per Day Per Day
day
Month (Lit) (Kg)
(Kg)
(Lit) (Lit) (Lit) (Kg) (Kg) (Kg) (Kg) (Kg) (Kg) (Kg) (Kg)
Atorvastatin 1818.3
1 4.50 150.00 1785.00 1793.49 24.89 12.38 49.67 1830.75 135.50 35.63 6.00 177.12 0.02 189.00
Calcium 8
7954.6
2 Telmisartan 3.00 100.00 7900.00 7930.74 23.87 96.57 38.21 8051.18 126.63 144.76 6.00 277.39 0.00 161.00
1
3 Zolmitriptan 0.18 6.00 280.80 283.20 4.60 287.80 24.29 8.41 312.09 4.98 24.29 0.00 29.27 3.81 9.60
Temafloxacin 3243.8
4 0.63 21.00 3183.60 3187.70 56.19 69.12 102.09 3313.01 45.91 69.12 0.00 115.03 16.10 68.46
Hydrochloride 9
5 Trovafloxacin 0.63 21.00 785.40 750.25 11.48 761.73 84.09 28.30 845.82 10.34 84.09 0.00 94.43 4.42 37.38
Selegiline
6 0.72 24.00 362.40 374.50 2.38 376.88 63.62 3.20 440.50 18.41 63.62 0.00 82.03 6.69 11.04
Hydrochloride
7 Safinamide 0.63 21.00 472.50 473.97 0.75 474.72 28.29 1.97 503.01 9.99 28.29 0.00 38.29 3.60 13.44
8 Landiolol 0.18 6.00 98.40 98.65 1.02 99.67 8.67 1.87 108.35 5.89 8.67 0.00 14.56 1.02 4.92
Sitagliptin
9 1.44 48.00 0.00 6.38 0.29 6.67 0.38 0.43 7.06 99.12 19.58 0.00 118.70 15.31 53.14
Hydrochloride
Perindopril
10 0.07 2.40 360.00 360.40 2.21 362.60 4.35 4.51 366.95 10.81 4.67 0.25 15.74 0.45 6.13
Erbumine
11 Cangrelor 0.07 2.40 75.84 75.46 2.25 77.72 2.56 3.58 80.28 3.37 2.90 0.00 6.27 1.00 1.48
12 Cilomilast 0.07 2.40 29.76 28.90 0.43 29.33 2.40 0.77 31.73 3.17 3.25 0.00 6.42 2.26 1.63
13 Sitafloxacin 0.07 2.40 28.80 30.28 1.44 31.71 1.98 1.06 33.69 5.25 2.31 0.00 7.56 0.37 1.68
Formoterol
14 0.05 1.80 0.00 0.00 0.00 0.00 0.00 0.00 0.00 3.76 0.72 0.00 4.48 0.16 2.30
Fumarate
Clevidipine
15 0.18 6.00 69.60 71.43 1.60 73.03 3.91 3.00 76.94 15.13 7.57 0.00 22.71 0.70 10.55
Butyrate
16 Udenafil 0.18 6.00 134.40 137.10 1.76 138.86 4.25 4.44 143.11 6.47 4.25 0.00 10.71 1.05 6.36
17 Argatroban 0.18 6.00 386.40 395.51 7.24 402.75 19.83 15.05 422.58 7.90 19.83 0.00 27.73 3.44 5.88
18 Balofloxacin 0.18 6.00 192.00 192.00 5.61 197.61 25.19 14.72 222.80 13.24 25.19 0.00 38.43 0.00 7.44
Continued..


PRODUCTION
Practical
Total
Water Organics
Water in Org.res./ Inorganics + Spent Total Solvent
Input Per In Total Total Semi solid EVA.Salts Process
Effluent TDS COD Carbon S.W. Loss
S.No Product Day Effluent Effluent Effluent
Tons / Per day Per Day
Per Day Per Day
Month (Kg) (Lit) (Kg)
19 Beraprost 0.18 6.00 204.00 221.32 7.83 229.15 12.09 12.34 241.24 6.17 12.09 0.00 18.26 0.27 2.76
20 Pazufloxacin 0.18 6.00 223.20 284.35 2.34 286.69 29.59 4.56 316.27 19.82 29.59 0.00 49.41 0.14 4.92
21 Talipexole 0.18 6.00 115.20 117.94 0.36 118.30 15.16 0.84 133.45 2.87 15.16 0.00 18.02 0.84 1.92
22 Almotriptan 0.18 6.00 274.50 297.94 4.63 302.58 37.71 9.52 340.29 9.09 39.21 1.08 49.39 5.88 12.36
Rizatriptan
23 0.18 6.00 248.40 276.80 3.21 280.01 29.65 6.15 309.67 6.43 30.01 0.66 37.10 1.96 9.15
Benzoate
24 Imipenem 0.36 12.00 530.40 532.23 13.11 545.33 43.20 32.38 588.54 28.12 43.20 0.00 71.32 0.15 18.96
25 Cefixime 0.36 12.00 352.80 367.53 4.76 372.29 15.90 9.83 388.20 31.14 16.50 0.60 48.25 0.00 8.76
26 Cefmetazole 0.36 12.00 447.60 455.22 10.20 465.42 6.70 10.33 472.12 23.49 6.70 0.00 30.18 1.43 9.06
27 Iloprost 0.36 12.00 360.00 359.13 13.82 372.95 19.82 26.70 392.77 24.13 19.82 0.00 43.95 0.32 12.43
28 Aripiprazole 1.05 35.00 1960.00 1960.00 25.20 1985.20 44.83 41.33 2030 89.92 50.32 4.20 144.4 0.00 42.35
29 Brivaracetam 0.63 21.00 64.26 69.59 0.58 70.16 10.92 0.77 81.08 16.39 10.92 0.00 27.31 7.32 12.39
Asenapine 234.9
30 0.63 21.00 1323.00 1340.09 24.83 1364.91 150.8 56.52 1515.7 84.08 150.82 0.00 7.48 17.09
Maleate 0
31 Ramipril 0.27 9.00 363.60 368.20 3.10 371.30 7.06 3.95 378.36 6.16 7.37 0.00 13.53 1.53 6.13
32 Zileuton 0.63 21.00 735.00 806.79 22.00 828.79 47.48 44.13 876.27 47.89 47.48 1.26 96.63 1.31 32.76
113.0
33 Vildagliptin 0.63 21.00 529.20 554.01 0.89 554.90 73.09 0.95 627.99 28.12 84.96 0.00 2.21 20.92
8
Palonosetron
34 0.18 6.00 207.75 212.82 4.39 217.21 3.88 8.23 221.09 5.79 3.88 0.00 9.66 0.30 5.55
Hydrochloride
Salmeterol
35 0.18 6.00 36.00 36.00 0.13 36.13 1.54 0.39 37.67 1.63 1.54 0.00 3.17 0.00 2.10
Xinafoate
36 Trandolapril 0.18 6.00 1839.60 1840.72 8.24 1848.96 29.10 16.89 1878.0 47.13 29.94 0.48 77.56 6.20 27.48
Continued..


PRODUCTION
Total Practical
Water Water Organics Total Org.res Inorganics
Spent Total Solvent
Input in in Efflu Total ./ Semi + Process
S.No Product TDS COD Carbon S.W. Loss
Per Per Day Effluent Effluent ent Effluent solid EVA.Salts
Tons / Per Day Per Per Day
day
Month Day (Kg)
(Kg)
(Lit)
37 Ecabapide 0.18 6.00 76.80 142.64 1.39 144.0 11.04 2.75 155.08 4.83 11.04 0.00 15.88 1.92 7.80
38 Zafirlukast 0.27 9.00 963.00 964.88 1.96 966.8 11.03 4.15 977.88 9.37 11.39 0.00 20.76 1.23 5.58
Darifenacin
39 0.27 9.00 180.00 180.00 0.82 180.8 3.06 1.23 183.88 5.48 3.06 0.00 8.54 0.00 2.61
Hydrobromide
Dapoxetine 1220.
40 3.00 100.00 19700.00 20082.78 255.70 20338 243.38 21558.78 563.80 1215.66 16.00 1795 273.42 392.00
Hydrochloride 30
41 Ibudilast 1.50 50.00 4287.50 4410.64 137.01 4547 306.4 153.04 4854.13 296.94 306.48 12.50 615.9 103.94 248.75
42 Mesalamine 3.00 100.00 1650.00 1693.96 10.36 1704 92.50 14.08 1796.82 0.00 92.50 14.00 106.5 17.18 0.00
43 Pregabalin 6.00 200.00 12000.00 12027.76 3.40 12031 298.9 7.18 12330.08 700.00 298.92 0.00 998.9 67.92 202.00
Sumatriptan
44 1.50 50.00 2880.00 2895.94 12.73 2908 74.68 26.79 2983.35 65.65 74.68 0.00 140.3 0.00 73.50
Succinate
45 Voriconazole 0.60 20.00 366.00 367.36 11.14 378.5 27.88 17.34 406.39 27.61 27.88 0.00 55.49 1.80 36.20
Gemifloxacin
46 1.44 48.00 1125.12 1118.39 26.99 1145 87.37 26.84 1232.75 47.47 87.37 5.38 140.2 16.45 49.63
Mesylate
Rasagiline
47 0.18 6.00 48.00 48.51 0.48 48.99 4.39 1.22 53.38 3.34 4.39 0.00 7.73 1.24 5.28
Mesylate
48 Valsartan 3.00 100.00 3300.00 3573.96 16.62 3590 367.9 28.66 3958.52 242.16 367.94 0.00 610.1 39.32 58.00
49 Zonisamide 3.00 100.00 3075.00 3201.28 15.65 3216 387.7 28.68 3604.70 29.00 387.78 35.00 451.7 30.05 201.25
50 Mirtazapine 1.50 50.00 2050.00 2099.77 50.14 2149 140.3 82.95 2290.22 96.13 140.31 14.00 250.4 12.65 133.00
51 Tigecycline 0.30 10.00 400.00 412.16 8.00 420 45.50 14.84 465.66 451.97 52.13 18.00 522.1 29.48 141.00
52 Efinaconazole 0.30 10.00 985.00 1009.59 38.26 1047 116.9 71.43 1164.80 124.73 126.95 0.00 251.6 0.00 69.00
Cetirizine
53 10.00 333.33 7600.00 7958.67 176.67 8135 414.0 330.47 8549.33 547.00 780.67 0.00 1327 21.67 790.00
Dihydrochloride
Continued..


PRODUCTION
Total Practical
Water Water Org.re
Organic Inorganic
Input in Total s./ Spent Total Proc Solvent
s in Total s+
S.no Product Per Effluen Effluen TDS COD Semi Carbon S.W. ess Loss
Per Effluent Effluent EVA.Salts
Tons / Day t Per t Per solid
day Day Per Day
Month Day
(Kg) (Kg)
(Lit)
Lomitapide
54 0.18 6.00 200.00 217.03 2.76 219.79 20.18 3.14 239.97 13.12 20.18 0.00 33.30 5.52 20.60
Mesylate
55 Ospemifene 0.30 10.00 803.00 793.84 4.80 798.64 152.15 9.46 950.79 56.74 184.37 0.00 241.11 3.06 25.60
56 Lumacaftor 0.18 6.00 1193.0 1299.9 12.39 1312.3 203.95 16.36 1516.33 23.06 203.95 0.00 227.02 58.4 41.20
57 Canagliflozin 0.75 25.00 996.67 978.64 14.68 993.32 317.27 28.75 1310.59 104.1 317.27 0.00 421.39 30.3 87.33
(S)-2-(tert-
Butoxycarbon
ylamino)-3-(4-
carbamoyl-
58 0.18 6.00 35.00 38.64 0.65 39.28 2.00 0.97 41.28 3.47 2.00 0.00 5.47 0.65 2.80
2,6-
dimethylphen
yl)propanoic
acid
59 Empagliflozin 0.75 25.00 1288.3 1280.6 10.30 1290.9 80.92 19.66 1371.86 25.86 80.92 0.00 106.77 21.8 38.47

3.9.2 Water requirement and Wastewater Generation and their Management /
Disposal
The permitted and proposed water requirement cum wastewater generation and its
treatment has been presented in Tables 6 & 7 respectively. The source of wastewater
generation will be mainly from the process, floor & reactor washes, utilities, Q.C, R&D,
scrubber and domestic waste. Total proposed wastewater will be around 199 KLD,
which will be segregated into HTDS/HCOD, Utilities & LTDS/LCOD and collected by
gravity into a collection tank separately. The individual collected wastewater will be
pumped to the storage/neutralization tank which is being constructed to above the
ground level - R.C.C lined tanks for neutralization. After neutralization the partly treated
wastewater will be send to the ETP- ZLD of 200 KLD.
Table 6: Existing water requirement and Wastewater generation

S.No Description Water Wastewater Treatment &
Requirement generation Disposal
(KLD) (KLD)
1 Process, Washings and 11.1 9.8 Effluent after
Scrubber HTDS neutralization
2 Boiler feed, Cooling Towers 5 1.7 sent to JETL
& DM Regenerations LTDS along with
3 Domestic 1 1 Domestic
LTDS effluent
Total 17.1 12.5

Table 7: Water balance and Segregation

Sl. Description Input (KLD) Output (KLD) Segregation type of
No. Wastewater
Fresh Recycled Generation / Total

Water Water Evaporation / Waste
Handling Loss water
1 Process 74.5 -- -1.5 76 * HTDS / HCOD
(15 products at a
time)
2 Washings 29 -- -- 29 LTDS/LCOD
(reactor,
centrifuges, nutch
filters, containers,
floor, etc.,)
3 Boiler 87 - 72 15 Utilities
(10,5&3TPH) (20% (Blow
Make down)
up)
4 Cooling 185 175 330 30

Towers (Make (Bleed)
6000 TR up)
5 DM 11 -- -- 11
Regeneration
6 Scrubber 5 -- -- 5 HTDS / HCOD
7 Q.C and R&D 1 -- -- 1 LTDS/LCOD
8 Domestic 40 -- 8 32 LTDS/LCOD
(800 nos at 50
lpcd)
9 Greenbelt 25 -- 25 --
(4.68 acres @ 5
KL/acre)
Total 457.5 175 433.5 199
Recycle – 175 KLD
Solvent condensate
632.5 632.5 0.5 KL & Moisture in
salt, sludge and
water loss 20 KL
Note: * 76 KLD is 80.5 in Tons (76 KL water & 4.5Tons of salts) as per material balance
The segregated effluent quantity, characteristics and treatment schematic flow was
briefly presented in Table 8.

Table 8: Effluent Quantity and Treatment Flow for as per segregation

Effluent Characteristics Quantity Treatment Flow
(KLD)
Process, DM & 92 Collection Equalization  Neutralization  Settling

Scrubber  Holding  Steam stripper  MEE along with HTDS
HTDS/HCOD & effluent  Condensate to ETP (biological treatment) 
(HTDS) Concentrate to ATFD
HTDS > 5000 mg/l
HCOD > 5000 mg/l ATFD Condensate to ETP (Biological Treatment) along
with domestic wastewater (septic tank overflow) 
Pressure Sand Filter  Activated Carbon Filter  R.O 
R.O rejects to MEE.
R.O Permeate & MEE Condensate to cooling tower
ATFD Salts to TSDF and stripped solvents to SPCB
authorized cement industries
Washings, Boiler, 75 Collection Equalization  Neutralization ETP

Cooling Tower, QC & (Biological Treatment) along with MEE Condensate
R&D
LTDS / LCOD
LTDS < 5000 mg/l
LCOD < 5000 mg/l
Domestic 32 Septic tank  Overflow to ETP (Biological Treatment)

The existing treatment system will be enhanced to treat the proposed quantities of
effluents which are being generated from the industry after expansion.
The proposed ETP schematic flow diagram is presented in (Annexure XIII). All stages
of treated tanks etc., of ETP will be constructed / installed above the ground with
anticorrosive lining to the tanks of ETP.
3.9.3 Hazardous/ Solid Waste Generation, Handling and their Disposal
Hazardous/ Solid waste will be segregated, detoxified and collected in the HDPE Drums
/ Bags and it will be stored in the covered and raised platform with Leachate collection
system.
The spillages of wastewater / solid wastes / raw material are possible and the risk of this
would be limited to within the premises of the manufacturing facility. Necessary safety &
Precautionary measures for spillage control will be practiced in the industry. The
proposed solid waste generation in the form of organic residue, inorganic & evaporation
salts and spent carbon are presented. The handling and disposal of the permitted &
proposed solid waste including other waste are presented in the Table 9&10.

Table 9: Existing Hazardous/Solid Waste Generation, Handling & Disposal details

S.No Description Quantity Disposal method
1 Process Organic Residue 639 Kg/day Shall be disposed to
2 Spent carbon 36 Kg/day TSDF/Authorised cement
industries for co-incineration
3 Inorganic & Evaporation salts 780.67 Shall be disposed to TSDF
Kg/day Dundigal for land fill.
4 ETP Sludge 20 Kg/day
5 Waste oil 30 Lit/Month Shall be disposed to authorised
6 Spent solvents 4000 Kg/day Reprocessors and recyclers
7 Mixed solvents 1000 Kg/day
8 Containers & containers liners 50 No/Month After complete detoxification
send to authorised agencies
Table 10: Proposed Hazardous/Solid Waste Generation, Handling & Disposal details
Proposed
Sl. Handling
Source Quantity Disposal
No. Method
(TPD)
1 Organic residue 3.7
2 Spent Carbon 0.14
Distillation Bottom HDPE
3 Residue 0.6 Drums
(1% of spent solvents)
4 Distillation mixed salts 2
Sent to APPCB
Inorganic & Authorized Cement
5 Evaporation salt 4.8 industries / TSDF
(Process)
Evaporation salt (Non- HDPE Bags
6 0.8
Process)
ETP Sludge (50 %
7 1.2
moisture)
Stored in
Sold to Cement Brick
8 Boiler Ash 30
covered
Manufacturers
area
Other Hazardous Waste generation from the Plant
9 a) Detoxified 500 Designated Disposed to APPCB
Container / Liners (Nos./month) covered Authorized agencies after
drums area complete detoxification
b) HDPE Carboys (Kg/m)

c) Fiber Drums
d) PP Bags
10 Spent solvents 62.3 KLD Stored in Recovery within the
(with moisture) Drums / premises duly sending the
(Solvents 59.3KLD + Tanks residue to TSPCB
water 3KLD) Authorized agencies
11 Recovered solvents 48 KLD Stored in Reuse in process / Send
from spent solvents Drums / to authorized recyclers
Tanks
12 Spent Mixed solvents 13.3 KLD Stored in Recovery within the
(11.3 KLD from SRS Drums / premises / Sent to
+ 2 KLD from ETP) Tanks TSPCB Authorized
agencies
13 Waste oils & Grease 5 KLPA Stored in Sent to TSPCB
Drums Authorized agencies for
reprocessing / recycling.
14 Used Lead acid 50 Nos./year Designated Sent to suppliers on buy-
Batteries covered back basis.
area
15 Misc. waste L.S Designated TSDF
(spill control waste) covered
area
Spent Catalyst
(Palladium carbon, Raney
Nickel, Rh(cod) (rr- Sold to suppliers on buy-
dipamp)bf4, Rhodium on Stored in
16. 1.2 TPD back basis / auth.
Carbon, Trifluoroacetic acid, Drums
Isobutyl Chloroformate, reprocessers.
Silver Benzoate, Carbo
benzyoxychloride)
Designated Sent to TSPCB Authorized
17 E waste 2 TPA
covered area agencies
Municipal Solid Waste HDPE Bags Disposed to Panchayat
18 0.2 TPD
(Canteen food waste) authorized agencies
19 Paper waste, & Misc. 0.2 TPD HDPE Bags Scrap venders
* Hazardous/ Solid waste quantities maximum on various combination i.e., maximum 15
products at a point of time
3.10 Schematic Flow Sheet for EIA Procedure
The schematic flow sheet for EIA procedure is depicted as (Annexure XIV).
4.0 Site Analysis
4.1 Connectivity
The proposed expansion project site is located at Sy. No. 202, 223 part 224-226 & 205
Notified Industrial area, Bonthapally, Jinnaram (M), Medak district of Telangana. The
project site is well connected by Road, Rail and Air to Hyderabad. There are many other

small and medium API Manufacturing units are also located in the same industrial area.
Hence, the availability of skilled manpower are plenty.
The Google map showing the Longitude and Latitude of Project location is shown in
Annexure XV.
4.2 Land Form, Land use and Land Ownership
The proposed project is in the existing manufacturing unit with additional land of 2.3 Ha
(23,000 Sq.M) and the industry is located in the Notified Industrial area, Bonthapally.
Total land is in possession of Project Proponent.
4.3 Topography
The Topographical map with 10 km buffer is enclosed as (Annexure XVI).
4.4 Existing Land Use Pattern
The proposed expansion activity will be adjascent to the existing manufacturing unit with
additional land. Land use pattern is presented in Table 11.
Table 11: Land Use Pattern of the Project Area

Land Use Area (sq.m)
Forests land (Type and density) Nil
Double Crop agricultural land Nil
Single crop agricultural land Nil
Waste land Nil
Grazing land Nil
Others (specify) Existing Industrial land + Additional 54,000
land
4.5 Existing Infrastructure
The existing infrastructure such as road network, water supply, facility for HTDS/HCOD
cum LTDS/LCOD treatment systems, member ship with CETP- JETL, Power supply
with backup power, Fire station, Hospitals, Telecommunication facility etc., are
available.

4.6 Soil Classification
In the proposed project area soil sampling has been done and analyzed to know the
existing scenario of the soil which is enclosed as (Annexure XVII).
4.7 Climate Data from Secondary Sources
The area enjoys pleasant, warm and dry climate. The coldest season is during
December and January, where the temperature touch a minimum of 13.6-15.8°C and
warmest period is during the month of April to May when the Mercury shoots up to 43 –
44.2°C.
The area experiences the maximum rainfall during the months of June to September
and a little rainfall during October and November due to North-East monsoon. Apart
from these, occasional rainfall is obtained from cyclonic storms and depression
originating in the Bay of Bengal. The normal annual rainfall of the area is around
951mm.
Groundwater quality has been monitored near the project site and the analytical report
is enclosed as (Annexure. XVIII).
4.8 Social Infrastructure
The existing industry is well connected by Road, Rail and Airways. The State Highway
Hyderabad- Narsapur will be 0.7 km from the project site. Other basic amenities such as
education centers, hospitals, and community halls are available.
5.0 Planning
5.1 Planning Concept
Type of Industry: API & its intermediates manufacturing industry.

Facilities: The Industry proposed for its expansion at existing premises with additional
land.
Transportation: Proposed and existing project is well connected to the Road, Rail and
Airways.
Town and Country Planning Classification: Bonthapally Notified Industrial area.

5.2 Population Projection
The proposal is for expansion of the existing industry with additional land and there is a
scope for marginal increase in the population in the vicinity as most of the workers
prefers to stay in nearby locations to avoid travelling from long distances. Hence, there
is a possibility of increase in population of the skilled and semi-skilled. The uneducated
local area people will be preferred for the unskilled jobs such as gardening, movement
of materials, etc. The educated youth will be employed as semi-skilled workers and
training will be provided. However, on the whole there is a possibility of little increase in
population of the area.
5.3 Land use Planning
The proposed expansion project is within the existing & extension land with an area of
5.4 Ha. Land use breakup of the Project area is given in Table 2.
5.4 Assessment of Infrastructure Demand
The proposed project site is located in Notified Industrial area, Bonthapally in Medak
District of Telangana and it is near to the state capital Hyderabad. The required
infrastructure will be available and procured at Hyderabad.
5.5 Amenities/Facilities
The Industry will continue to provide and upgrade the following amenities / facilities in
the proposed expansion project.
• Potable drinking water

• Training block
• Laying of Black top / Concrete internal roads
• Fire hydrant facility
• Eye/body wash showers
• First Aid kits at all prominent places.
• Rest Room for employees
• Sitting facilities for those employees who do their work standing and ergonomically
designed sitting facilities for those who do their work sitting
• Pre-employment and routine medical examinations and the necessary follow up
actions
• Communication systems like Phone, Internet with safety measures, etc.

6.0 Proposed Infrastructure
6.1 Industrial Area
The expansion project is coming within the existing unit with additional land. Total area
of 5.4 Ha (54,000 sq.m) out of which about 1.44 Ha (14,474 sq.m) (26.8%) is plinth area
consisting of production blocks, warehouses & stores, utilities, R&D, QC, and
administrative block etc., about 1.43 Ha (1,4300sq.m) (26.48%) for roads & open and
vacant area about 0.63 Ha (6,326) (11.71%) and Greenbelt area about 1.89 Ha
(18,900) sq.m (35%).
6.2 Residential Area
There will be no residential area within the proposed expansion project site.
6.3 Greenbelt
The expansion project activity is in the existing unit with additional land totaling 5.4 Ha.
Out of which, about 1.89 Ha (18,900 sq.m) is earmarked for Greenbelt area.
6.4 Social Infrastructure
As a Corporate Social Responsibility (CSR), industry will contribute for development of

nearby areas in association with the members of Industrial area.
6.5 Connectivity
The proposed expansion project site is located at Notified Industrial area, Bonthapally,
Jinnaram (M), Medak district of Telangana. The site is well connected by Road, Rail and
Air to Hyderabad.
The nearest railway station is Dablipur at 10.2 Km & major at Secunderabad at an aerial
distance of 29 km from the site. The Rajiv Gandhi International airport is being located
at an aerial distance of 47 km from the site.
6.6 Drinking Water Management

Potable drinking water will continue to be provided to all employees. The source of
drinking water is Groundwater.

6.7 Sewerage System
Sewage will be generated from the Canteen and Toilets, which will be collected into
sewage collection tank through pipelines and septic tank respectively. Overflow of these
tanks will be sent to ETP – ZLD system which needs to be upgraded to meet the
expansion project demand.
6.8 Industrial Waste Management
Existing storage system needs to enhance to meet the expansion project demand. The
management of these wastes is to be handled very sensitively and by adopting proper
segregation techniques.
Liquid Waste Management: The liquid wastes from the various industrial activities will
continue to be segregated and send to ETP-ZLD.
6.8.1 Process Emissions Management
Manufacturing of API and its intermediates will result in gaseous emissions. The
proposed product-wise process emissions, their quantity and treatment are presented in
Table 12. Maximum Process emissions from campaign basis for proposed products are
given in Table 13. The Proposed gaseous emissions will be scrubbed in two stages with
water and caustic solution based on the characteristics of gases.

Table 12: Proposed Process Emissions-Product wise
Gas
S.
Product Process Emission emissions Treatment
No
/ Day(Kg)
1 Atorvastatin Calcium Hydrogen 0.02 Diffused with flame arrestor
2 Telmisartan Nil
3 Zolmitriptan Carbon Dioxide 3.81 Dispersed into atmosphere
4 Temafloxacin Hydrochloride Carbon Dioxide 15.52 Dispersed into atmosphere
Hydrogen 0.58 Diffused with flame arrestor
5 Trovafloxacin Hydrogen 4.42 Diffused with flame arrestor
6 Selegiline Hydrochloride Hydrogen Chloride 6.69 Scrubber with water / caustic sol.
7 Safinamide Carbon Dioxide 3.6 Dispersed into atmosphere
8 Landiolol Carbon Dioxide 1.02 Dispersed into atmosphere
9 Sitagliptin Hydrochloride Hydrogen Chloride 10.46 Scrubber with water / caustic sol.
Nitrogen 4.56 Dispersed into atmosphere
10 Perindopril Erbumine Hydrogen 0.09 Diffused with flame arrestor
Carbon Dioxide 0.36 Dispersed into atmosphere
11 Cangrelor Hydrogen Chloride 0.22 Scrubber with water / caustic sol.
12 Cilomilast Oxygen 0.33 Dispersed into atmosphere
Hydrogen Chloride 1.93 Scrubber with water / caustic sol.
13 Sitafloxacin Carbon Dioxide 0.37 Dispersed into atmosphere
14 Formoterol Fumarate Hydrogen 0.16
15 Clevidipine Butyrate Carbon Dioxide 0.7 Dispersed into atmosphere
16 Udenafil Carbon Dioxide 0.33 Dispersed into atmosphere
17 Argatroban Carbon Dioxide 3.19 Dispersed into atmosphere
Ammonia 0.24
18 Balofloxacin Nil
19 Beraprost Hydrogen 0.27 Diffused with flame arrestor
20 Pazufloxacin Hydrogen 0.14 Diffused with flame arrestor
21 Talipexole Carbon Dioxide 0.74 Dispersed into atmosphere
22 Almotriptan Hydrogen Chloride 5 Scrubber with water / caustic sol.
Nitrogen 1 Dispersed into atmosphere
23 Rizatriptan Benzoate Nitrogen 1.96 Dispersed into atmosphere
24 Imipenem Hydrogen 0.15 Diffused with flame arrestor

25 Cefixime Nil
26 Cefmetazole Hydrogen Chloride 1.43 Scrubber with water / caustic sol.
27 Iloprost Hydrogen 0.32 Diffused with flame arrestor
28 Aripiprazole Nil
29 Brivaracetam Carbon Dioxide 5.28 Dispersed into atmosphere
Ammonia 2.04 Scrubber with water / dil. HCl sol.
30 Asenapine Maleate Carbon Dioxide 5.76 Dispersed into atmosphere
Hydrogen 1.73 Scrubber with water / caustic sol.
31 Ramipril Carbon Dioxide 1.49 Dispersed into atmosphere
32 Zileuton Hydrogen 1.31 Diffused with flame arrestor
33 Vildagliptin Carbon Dioxide 2.21 Dispersed into atmosphere
34 Palonosetron Hydrochloride Hydrogen 0.03 Diffused with flame arrestor
35 Salmeterol Xinafoate Nil
36 Trandolapril Hydrogen 0.48 Diffused with flame arrestor
37 Ecabapide Carbon Dioxide 1.92 Dispersed into atmosphere
38 Zafirlukast Carbon Dioxide 1.2 Dispersed into atmosphere
39 Darifenacin Hydrobromide Nil
40 Dapoxetine Hydrochloride Hydrogen Chloride 241.62 Scrubber with water / caustic sol.
41 Ibudilast Hydrogen Chloride 74.84 Scrubber with water / caustic sol.
Carbon dioxide 29.1 Dispersed into atmosphere
42 Mesalamine Hydrogen 1.68 Diffused with flame arrestor
43 Pregabalin Carbon dioxide 67.92 Dispersed into atmosphere
44 Sumatriptan Succinate Nil
45 Voriconazole Hydrogen 1.8 Diffused with flame arrestor
46 Gemifloxacin Mesylate Carbon Dioxide 16.45 Dispersed into atmosphere
47 Rasagiline Mesylate Carbon Dioxide 1.24 Dispersed into atmosphere
48 Valsartan Carbon Dioxide 39.32 Dispersed into atmosphere
49 Zonisamide Carbon Dioxide 28.6 Dispersed into atmosphere
Ammonia 1.45 Scrubber with water / dil. HCl sol.
50 Mirtazapine Ammonia 5.84 Scrubber with water / dil. HCl sol.
Hydrogen Fluoride 6.81 Scrubber with Caustic solution

51 Tigecycline Hydrogen Chloride 24.91 Scrubber with water / caustic sol.

52 Efinaconazole Nil
53 Cetirizine Dihydrochloride Hydrogen Chloride 21.67 Scrubber with water / caustic sol.
54 Lomitapide Mesylate n-Butane 3.73 Diffused with flame arrestor
55 Ospemifene Hydrogen 1.08 Diffused with flame arrestor
56 Lumacaftor Hydrogen Chloride 7.5 Scrubber with water / caustic sol.
57 Canagliflozin Carbon Dioxide 29.33 Dispersed into atmosphere
58 (S)-2-(tert- Hydrogen 0.65 Diffused with flame arrestor
Butoxycarbonylamino)-3-(4-
carbamoyl-2,6-
dimethylphenyl)propanoic
acid
59 Empagliflozin Carbon Dioxide 21.81 Dispersed into atmosphere
Table 13: Maximum Quantity of Process Emissions for Proposed Products
Sl. Process Maximum Quantity on Treatment

No. Emission various combinations
(kg/day)
Proposed
1 HCl 414.23 • Scrubber with water / caustic sol.
2 NH3 9.53 • Scrubber with water / dil. HCl sol.
3 CO2 347.11 • Dispersed into atmosphere
4 N2 7.9242 • Dispersed into atmosphere
5 O2 0.33 • Dispersed into atmosphere
6 H2 23.7 • Diffused with flame arrestor
7 HF 6.81 • Scrubber with Caustic solution
8 n-Butane 3.73 • Diffused with flame arrestor

6.8.2 Solvent management for effective recovery:
The industry will take measures for reduction of fugitive emissions and for further
reduction industry provide vent condensers to the tanks.
Chilled brine will be carried out to condensate the solvent vapour and to the
receivers of the solvent vapors which ensures the maximum recovery
Solvent vapours from the centrifuge and catch pots will be connect to vent
condensers
The height of the solvent receiver tank vent is above production block roof level
and the diameter is 20 mm.
Flame proof fitting/ equipment /pumps/lighting will be used wherever solvents are
used.
The solvent storage tanks will be provided with breather valve to prevent losses.
Solvent Solvent
Solvent Solvent Solvent Solvent
in in Org.
Product Input loss Recovery Recovery
Effluent waste
KLD KLD KLD KLD KLD %

Proposed Products (Maximum 15 Products at a point of time)
Combination-1 63430.4 217.8 959.1 2840.8 59318.6 93.5
Combination-2 54191.2 235.8 810.6 2353.7 50740.0 93.6
Combination-3 60417.0 211.3 965.3 2661.4 56512.0 93.5
Combination-4 63287.4 210.6 962.6 2856.5 59163.7 93.5
6.8.3 Emissions – Utilities
Boiler and DG sets are the two main sources contributing to air emissions from the
plant. Industry is proposing –10 TPH; 5 TPH and 3 TPH Coal fired boiler & 2 Lakh K.cal
coal fired TFH. Existing 1TPH coal fired boiler will be dismantled. The proposal to install
1010 KVA X 3 No; 650 KVA; 380 KVA for the expansion and the existing 125 KVA DG
Set will be dismantled. The air emissions from the boiler, TFH & D.G. sets are given in
Table 14.

Table 14: Stack Emission Details

Stack PM SO2 NO2
Temperature Flue Gas Exit Gas
Source Height Diameter Flow rate Velocity
o
(m) (m) ( C) (m3/hr) (m/sec) kg/hr
Boilers
10 TPH 40 0.8 150 266604 14.71 1.35 14.17 8.1
5 TPH 30 0.6 150 13307 13.1 0.675 7.08 4.05
3 TPH 30 0.5 150 7984 11.3 0.405 4.25 2.43
Proposed Coal fired thermic fuel heater
2 lakh
Kcal/hr 30 0.15 150 770 4.36 0.052 0.522 0.365
TFH
Proposed D.G sets
1010 KVA 11 0.4 150 5702 12.6 0.064 1.26 1.36
1010 KVA 11 0.4 150 5702 12.6 0.064 1.26 1.36
1010 KVA 11 0.4 150 5702 12.6 0.064 1.26 1.36
650 KVA 9 0.3 150 3668 14.42 0.041 0.813 0.872

380 KVA 8 0.25 150 2145 12.14 0.024 0.475 0.509
** The existing 1 TPH &125 KVA will be dismantled
Note: Coal calorific value is 4500 kcal/Kg of coal with 0.5% sulphur
Coal is being used as a fuel for steam generation to the boilers, Particulate Matter (PM),
Sulphur dioxide (SO2) and Oxides of Nitrogen (NO2) will be the major air pollutants. The
various measures proposed to minimize the pollution from the boiler are Multicyclone
separator & Bag filter will be installed to control the particulate (PM) emissions within
statutory limit of 115 mg/Nm3. To facilitate wider dispersion of pollutants, 40 / 30 m
height stack will be installed.
The NO2 emissions from the boiler will be controlled by controlling combustion
measures, which will be approached by way of low NOx burners or by air stagging in
boiler. The NO2 emissions will be restricted to below 500 mg/Nm3.

Stack will be provided to the proposed DG sets of 1010 KVA X 3 No; 650 KVA &380
KVA as per CPCB Guidelines. Fugitive dust will be controlled by adopting dust
extraction and dust suppression measures.
6.8.4 Noise Environment
Compressors, Boiler and DG set will be the major noise generating units in the plant.
Out of these the generator will be functioning at the time of power failure. There is no
need for the workers to be near this unit continuously. The noise levels of the DG set
will be well within the limits as these will be installed with acoustic enclosures. However
the workers in this area will always provide with ear muffs.
All the equipment in the plant would be designed to have a total noise level not
exceeding 85-90 dB(A) as per the requirement of OSHA (Occupational Safety and
Health Administration) standards.
The proposed expansion project site is located in Notified industrial area Bonthapally,
which is about 900 m from nearest habitation Shapurnagar village; no impact of noise
will be felt at this village. As per factory act, under the general health checkup scheme,
the workers will be examined for any Noise Induced Hearing Loss (NIHL) by a trained
ENT Doctor. The noise levels in the work place environment will be monitored
periodically and action will be taken in the form of regular maintenance schedule to
reduce noise and vibration in generating sources.
6.9 Hazardous / Solid Waste Management
Hazardous / Solid waste mainly segregated into process organic residues, inorganic
salts and spent carbon. These wastes are hazardous in nature as they emanate from
the chemical reactions or un-reacted chemical wastes. The organic residues & Spent
carbon can be disposed off to Cement plants as recommended by CPCB for use as
alternate fuels either in the solid or liquid form. Inorganic salts are to be sent for landfill
at HWMP – TSDF.
6.10 Power Requirement & Supply / Source
Power supply of 5000 KVA has been drawn from the nearby sub-station of TSSPDCL.
The proposed 4060 KVA DG set will be used as standby facility in case of in power
failure.

7.0 Rehabilitation and Resettlement (R&R) Plan
The proposed expansion land is in Notified Industrial area at Bonthapally. Therefore, No

Rehabilitation and Resettlement applicable to this project site.
8. Project Schedule & Cost Estimates
8.1 Time Schedule for the Project Construction
The timelines for commencement of proposed expansion construction activity will be

from December 2016 as it is expected that the expansion project will be in a position to
obtain Environmental Clearance and Consent for Establishment from the State Pollution
Control Board. In 2016-17, the commercial production is expected to be commenced.
The total expansion project investment is of Rs. 110 Crore including existing Rs.12
Crore investment.
8.2 Estimated Project Cost
Overall estimated cost involved in the total project (existing and proposed) like land,
building, plant & machinery is Rs.110 Crore (Rs. 12 Crore existing & Rs. 98 Crore
proposed investment). The capital cost allocated towards environmental pollution
control measures towards proposed are Rs 11 Crore (including Rs. 1.43 Crore) and the
recurring cost will be Rs. 9.58 Crore per annum.
9.0 Analysis of proposal (Final Recommendations)
• M/s. Maithri Drugs Pvt. Ltd., proposes to expand its API and its Intermediates
manufacturing facility within existing facility with an additional land of 2.3 Ha
(23,000 sq.m) totaling 5.4 Ha at Sy. No. 222,223part, 224-226&205 (Notified
Industrial area), Bonthapally, Jinnaram (M), Medak District of Telangana
• Under the Corporate Social Responsibility the Industry will continue to develop a
policy of developing the villages in the vicinity by identifying the requirements.
• No adverse effect on environment is envisaged as proper mitigation measures will

be taken up.

• Industry will strengthen the existing Safety, Health & Environment Department and
also continue to engage recognized laboratories to carry out all necessary
monitoring parameters for its activities.
• The segregated (HTDS / LTDS) wastewater will regularly analyzed before and
after treatment in ETP-ZLD.
• Qualified staff will be appointed for the purpose of Operation and Maintenance of
the pollution control facilities.
• Stand-by facilities will be provided to all the pumps so as to ensure fail proof
treatment, handling and disposal.
• The capital cost allocated towards environmental pollution control measures

towards proposed are Rs 11 Crore (including Rs. 1.43 Crore) and the recurring cost
will be Rs. 9.58 Crore per annum.
9.1 Budgetary allocation for Pollution Control Measures
The management will allocate adequate funds in its budget to fully meet the stated
objectives of the environmental policy. The proposed & the existing capital equipment
for better environmental management which includes of up-gradation of ETP to ZLD,
pipelines and channels for wastewater discharge, greenbelt development and the up
gradation of environment laboratory. The break-up of budgetary allocation for various
environmental control measures is presented in Table 15.

Table 15: Budgetary allocation for Pollution Control Measures

Capital Cost Recurring Capital *Recurring
S. Pollution Control in Crore Cost Cost Cost
No. Equipment In Crore in Crore In Crore
(Existing) (Proposed)
Air Pollution Control
1 Multicyclone separator &
0.10 0.04 0.8
Bag filter with stack
0.12
2 Scrubbers 0.05 0.02 0.6
3 Vent condensers 0.09 0.02 0.8
4 Water Pollution Control
ETP Civil, mechanical
equipment’s & MEE 0.10 1.80 5.0 5.96
system
5 Noise Pollution Control
Silencers / acoustic
0.04 0.04 0.10 0.04
enclosures
6 Solid Waste Management
Covered Platform with
0.10 0.03 0.15 2.55**
leachate collection system
7 Greenbelt Development 0.05 0.04 0.2
8 Occupation Health and
0.10 0.6
Safety
9 Fire Management 0.10 0.04 1.0
0.91
10 Dyke walls and Storm
0.10 0.02 0.20
water drains
11 Environmental Laboratory 0.10 0.09 0.40
12 Misc. 0.50 0.15 1.15
Total Cost on Pollution Control
1.43 2.29 11.0 9.58
equipment’s
*Recurring cost includes manpower, consumables, maintenance, energy charges per

annum
** Includes the handling, transportation, landfill/incineration charges

ANNEXURES
ANNEXURE - I
42
ANNEXURE - I
43
ANNEXURE - I
44
ANNEXURE - I
45
ANNEXURE - II
46
ANNEXURE - II
47
ANNEXURE - II
48
ANNEXURE - II
49
ANNEXURE - II
50
ANNEXURE - II
51
ANNEXURE - II
52
ANNEXURE - II
53
ANNEXURE - II
54
ANNEXURE - II
55
ANNEXURE - III
56
ANNEXURE - III
57
ANNEXURE - III
58
ANNEXURE - III
59
ANNEXURE - III
60
ANNEXURE - III
61
ANNEXURE - III
62
ANNEXURE - IV
63
ANNEXURE - IV
64
ANNEXURE - IV
65
ANNEXURE - IV
66
ANNEXURE - V
67
ANNEXURE - VI
68
ANNEXURE - VI
69
ANNEXURE - VI
70
ANNEXURE - VI
71
ANNEXURE - VI
72
ANNEXURE - VI
73
ANNEXURE - VI
74
ANNEXURE - VII
75
ANNEXURE - VII
76
ANNEXURE - VII
77
ANNEXURE - VII
78
ANNEXURE - VII
79
ANNEXURE - VIII
GOVERNMENT OF ANDHRA PRADESH

ABSTRACT
Promotion of Industries – Declaring Gaddapotharam (Kazipally), Bonthapally &
Gundlamachnoor areas as Notified Industrial Areas – Orders Issued.
--------------------------------------------------------------------------------------------------------------------
INDUSTRIES & COMMERCE (IP) DEPARTMENT
G.O.Ms. No. 120 Dated. 22.10.2013.
Read the following:
1. Letter No. Nil, dated 14/08/2012 of the President, Model Industrial Association,
Hyderabad.
2. Letter No. Nil, dated 02/09/2013 of the President, Bulk Drug Manufacturers
Association, Hyderabad.
3. Recommendation of the Committee constituted for this purpose
4. Single File No.29/1/2012/13884 of Commissioner of Industries, dated
11.10.2013
5. D.O.Lr.No.15/36/2013/EP (Engg./Pharma), Dated:30-04-2013 of the Commerce
Secretary to Government of India
6. G.O.Ms.No.64,EFS&T(ENV),Dated:25/07/2013
***
ORDER:
1. In the reference 1st & 2nd read above, the President, Model Industrial Association,
Hyderabad and President, Bulk Drug Manufacturers Association (BDMA) have submitted
representations for declaration of Gaddapotharam (Kazipally), Bonthapally &
Gundlamachnoor industrial areas as the notified industrial areas, informing that the members
of their associations have set-up Chemical and Pharma industries in five industrial pockets in
the area viz. Khazipally-Gaddapotharam, Bonthapally, Bonthapally-Domadugu, Borapatla
and Gundlamachnoor, way back in 1990s after getting all the required permissions and
approvals including Consent for Operations (CFO). He has requested the Government for
notifying the said locations as industrial areas so as to facilitate the industries to avail various
benefits being announced by the Central Government under the Industrial Infrastructure Up-
gradation Scheme (IIUS) and also incentives announced, from time to time, by the State
Government, as these areas have immense potential to develop further as a major
manufacturing hub for pharmaceuticals and related chemical products.
]
2. It is further be noted that Andhra Pradesh, particularly Hyderabad, has emerged as a

major player in the Bulk Drug Industry sector. There are about 266 bulk drug manufacturing
companies in Andhra Pradesh, of which 90 per cent are located around Hyderabad.
Hyderabad is contributing about 35% of the country’s bulk drug production and has been
labeled as Bulk Drug capital of India. The Commerce Secretary, Government of India, in the
reference 5th cited has stated that the share in export of bulk drugs and pharmaceuticals from
the state of Andhra Pradesh is about 30% of the total exports from the country and
recommended for expansion of the existing units subject to compliance of Andhra Pradesh
Pollution Control Board norms in order to give further boost to the exports from this sector.
3. In the reference 6th read above the Government permitted the existing Bulk Drug and
Bulk Drug intermediates manufacturing units only subject to the installations of Zero Liquid
Discharge (ZLD) facilities by such units to go for expansion duly complying with all extant
environmental and other norms.
4. The matter was carefully examined by an expert committee constituted by the

Commissioner of Industries which submitted its recommendations vide the reference 3rd read
above. Based on their recommendations the Commissioner of Industries has submitted his
recommendations vide the reference 4th read above.
80
ANNEXURE - VIII
-2-
5. The Government after careful examination of the matter and in view of the
recommendations of the Commissioner of Industries, A.P., Hyderabad and under various
provisions of the Industrial Investment Promotion Policy 2010-15 (IIPP 2010-15), hereby
decided to notify the following areas as Notified Industries Areas, as these areas are already
located within Manufacturing Zones as notified in the master plan of Hyderabad
Metropolitan Development Authority and more than 140 industries are operating in these
areas with all the required clearances including Consent for operations (CFO).
S.N Location Village Survey Nos Area in

Full Part Ha.
1 Kazipally- Kazipally --- 180 99.41
Gadda
potharam Gaddapotharam 12 to 16 7 to 10 , 25 , 28, 52 138.3
Area
Alinagar 5, 12 to 17,20 to 9,11,18,19,27/1,30, 97.71

27,30, 31, 32, 36, 32 to 34, 41, 42, 47,
41 ,43 to 48 52
2 Bonthapally Bonthapally 3,4,631,632,634, 2,599,629,630, 633, 56.56

635
636, 637, 639,660
3 Bonthapally Bonthapally 205-208,213- 192,202,203, 204, 40.76

- 224, 227-229,
209,
Domadugu 231, 232, 254, 225,226,233,235-
Area 256, 265, 272, 238, 250-
471, 472, 490/2253,255,257-262,
264,266-271, 273,
274, 466-470, 473-
475,487-489,
490/1,497, 626
Domadugu 290, 347, 348, 289, 291, 292, 341 , 38.40
351, 354, 355, 345, 346, 349, 350,
357-363, 365 352, 353, 356 ,366,
367, 369, 371, 372
4 Bodupatla Bodupatla 4 to 15, 24, 28, 3,16,17,30,31,269 32.304

29, 374, 375, to 272, 373, 376 to
379/2, 388-390, 378, 385, 391,397
392-396
6. Further, it is noted that though the Industries located in Gundlamachanoor have

converted their lands for industrial use, the same has not been reflected in the master plan
of Hyderabad Metropolitan Development Authority as manufacturing zone. The Bulk Drug
Manufacturers Association vide their Letter No. BDMA/Commissioner/MPDA/2013-14
dated. 21-09-2013 have requested the Commissioner, Hyderabad Metropolitan Development
Authority to correct the anomaly by notifying the above location as Manufacturing Zone.
Therefore, the following location is also notified as Industrial area subject to notification of
the area as Manufacturing Zone by the Hyderabad Metropolitan Development Authority in
their master plan.
1 Gundla Gundla 374, 375, 376, 377, 44.51

machnoor machnoor 378 & 379
81
ANNEXURE - VIII
-3-
7. The following conditions will apply:

(a) All the industries coming within these locations must have a valid Consent for
Operation (CFO) issued by A.P. Pollution Control Board as on the date of notifying as
Industrial Area.
(b) The location including the areas of different survey numbers shall be within the
manufacturing zone of the Hyderabad Metropolitan Development Authority Master
Plan.
(c) All other clearances, approvals, approvals under various applicable laws, acts and
rules of all relevant departments as required shall be applicable to all the industries
coming within these notified locations; and
(d) All new industrial units proposed in the proposed Industrial Areas to be notified and
those attract the provisions of Water (Prevention and Control Pollution) Act, 1974 and
Air (Prevention and Control Pollution) Act, 1981, shall invariably obtain prior
Consent for Establishment (CFE) from A.P. Pollution Control Board.
8. The Commissioner of Industries, Hyderabad shall take necessary action, in the matter.
(BY ORDER AND IN THE NAME OF THE GOVERNOR OF ANDHRA PRADESH)
K.PRADEEP CHANDRA,
PRINCIPAL SECRETARY TO GOVERNMENT AND
COMMISSIONER FOR INDUSTRIAL PROMOTION
To
The Commissioner of Industries, A.P., Hyderabad.
The MA & UD Department
The EFS & T Department
The Member Secretary, Andhra Pradesh Pollution Control Board, Hyderabad
The Vice Chairman & Managing Director, APIIC, Hyderabad.
The PR & RD Department
The DT & CP Department
The Revenue (CT) Department.
The Energy Department.
The Irrigation (Reforms) Dept.
The Ind. & Com. (INF) Department.
The Chairman & Managing Director, APTRANSCO., Hyderabad
The Managing Director, APCPDC Ltd., Hyderabad
The District Collector, Medak District.
//FORWARDED::BY ORDER//
SECTION OFFICER
82
ANNEXURE - IX
PRODUCT : Atorvastatin Calcium
Description :
Stage-1 : tert -Butyl-2-[(4R,6S)-6-(cyano methyl)-2,2-dimethyl-1,3-dioxan-4-yl] acetate on reduction with
Hydrogen on Palladium Carbon in presence of Methanol solvent medium gives tert -Butyl-2-[(4R,6
(amino ethyl)-2,2-dimethyl-1,3-dioxan-4-yl] acetate.
Stage2 : Aniline on condensation with Dimethyl Carbonate in presence of 2-Methyl-2-butanone in Methanol
medium gives 4-Methyl-3-oxo-N-phenyl pentanamide.
Stage-3 : 4-Methyl-3-oxo-N-phenyl pentanamide upon reaction with Benzaldehyde in presence of Potassium
Carbonate in Acetone and Toluene solvent media gives 2-Benzylidene-4-methyl-3-oxo pentanoic acid
phenyl amide.
Stage-4 : 2-Benzylidene-4-methyl-3-oxo pentanoic acid phenyl amide on reaction with t- Butyl-2-[(4R,6S)-6
(aminoethyl)-2,2-dimethyl-1,3-dioxan-4-yl] acetate in presence of Fluorobenzaldehyde and p-Toluene
Sulfonic acid in Isopropyl Alcohol and Toluene solvent media gives Atorvastatin ester.
Stage-5 : Atorvastatin ester undergoes hydrolysis in presence of Sulfuric acid in Methanol solvent medium
forms Atorvastatin.
Stage-6 : Atorvastatin upon salt formation with Calcium Acetate in presence of Isopropyl Alcohol solvent
medium and gets purified with Carbon to obtain Atorvastatin Calcium.
83
ANNEXURE - IX
Flow Chart
tert-Butyl-2-[(4R,6S)-6-(cyano
methyl)-2,2-dimethyl-1,3- Sol.Recovery
dioxan-4-yl] acetate Evaporation Loss
Palladium Carbon Stage I Organic Residue
Methanol Inorganic Solid Waste
Hyflo Process Emissions
Hydrogen
Aniline
Dimethyl Cabonate Sol.Recovery
2-Methyl-2-Butanone Evaporation Loss
Stage II
Sulfuric acid Effluent
Methanol Organic Residue
Water
Stage-2
Benzaldehyde Sol.Recovery
Potassium Carbonate Evaporation Loss
Stage III
Acetone Effluent
Toluene Organic Residue
Water
Stage-3
Fluorobenzaldehyde
Stage-1 Sol.Recovery
Toluene Stage IV Evaporation Loss
p-Toluenesulfonic acid Effluent
Isopropyl Alcohol Organic Residue
Water
Atorvastatin ester Sol.Recovery

Sulfuric Acid Evaporation Loss
Stage V
Methanol Effluent
Water Organic Residue
Atorvastatin Sol.Recovery
Calcium Acetate Evaporation Loss
Isopropyl Alcohol Stage VI Organic Residue
Carbon Inorganic Solid Waste
Hyflo Spent Carbon
Atorvastatin Calcium
84
ANNEXURE - IX
PRODUCT : Telmisartan
Description :
Stage-1 : 4-Methyl-6-(1-methylbenzimidazol-2-yl)-2-propyl-1H-benzimidazole reacts with Methyl 2-[4-

(bromomethyl) phenyl]benzoate in presence of Potassium Hydroxide and Hydrogen Bromide in Methanol,
Acetone and Acetonitrile solvent media to get Stage-1 Intermediate.
Stage-2 : Stage-1 Intermediate reacts with Potassium Hydroxide in the presence of Acetic acid in Acetonitrile
solvent medium to give Telmisartan (Crude).
Stage-3 : Telmisartan (Crude) is purified with Ammonia solution in the presence of Acetic acid and Activated
Carbon in Ethanol solvent medium to form Telmisartan (Pure).
Flow Chart
4-Methyl-6-(1-methyl
benzimidazol-2-yl)-2-propyl-1H-
benzimidazole
Methyl 2-[4-(bromomethyl) Sol.Recovery
phenyl]benzoate Evaporation Loss
Potassium Hydroxide Stage I Effluent
Acetone Organic Residue
Hydrogen Bromide
Acetonitrile
Hyflo
Stage-1
Potassium Hydroxide Sol.Recovery
Acetonitrile Stage II Evaporation Loss
Acetic acid Effluent
Telmisartan (Crude)
Ethanol Sol.Recovery
Ammonia (25%) Solution Evaporation Loss
Stage III
Activated Carbon Organic Residue
Water Spent Carbon
Telmisartan
85
ANNEXURE - IX
PRODUCT : Zolmitriptan
Description :
Stage-1: Methyl-3-(2-aminoethyl)-5-{(2-Oxozolidin-4-yl)methyl)-1H-Indole-2-carboxylate was treated with Methyl

Iodide in presence of Potassium Carbonate in Acetone medium. Heat the reaction mixture to reflux and maintain
for 2 hours. After completion of the reaction, filter and distilled off the reaction mixture. Wash the mixture with
water and then extracted with Ethyl Acetate. Distilled off the organic layer completely to obtain Stage-1
Compound.
Stage-2: Stage-1 Compound was reacted with Acetic acid and then with Hydrochloric acid. After completion of
reaction, the reaction mixture pH was adjusted with Sodium Hydroxide. Then centrifuged the precipitated solid
and dried to obtain the Zolmitriptan.
Flow Chart
Methyl-3-(2-aminoethyl)-5-{(2-
oxozolidin-4-yl)methyl)-1H-
indole-2-carboxylate Sol.Recovery
Methyl Iodide Evaporation Loss
Stage I
Potassium Carbonate Effluent
Ethyl Acetate Process Emissions
Water
Stage-1
Hydrochloric acid (35%) Stage II Organic Residue
Sodium Hydroxide Process Emissions
Water
Zolmitriptan
86
ANNEXURE - IX
PRODUCT : Temafloxacin Hydrochloride
Description :
Stage-1 : Added Triethylamine followed by Di-tert-butyl dicarbonate to a solution of Methylene Dichloride and 1-
(2,5-difluoro-4-(3-methylpiperazin-1-yl) phenyl) ethanone hydrochloride at 0-5°C. Allowed reaction mass
temperature to 25-30°C. Maintained the reaction mass for 4hrs at 25-30°C, then washed the reaction mass with
Phosphoric acid solution followed by Sodium Bicarbonate and Sodium Chloride solution. Concentrated the
organic layer and isolated in Cyclohexane to form Stage-1 Compound.
Stage-2 : Added Sodium Hydride into a solution of Diethyl Carbonate and Stage-1 Compound in to clean and dry
reactor (take all safety precautions before charging Sodium Hydride, Nitrogen blanket is maintained through out
maintenance), Heated to the raection mass to 80°C and maintained the reaction mass for 2hrs at the same
temperature then cooled to 10-15°C. Added Acetic acid and water into the reaction mass and extracted the
compound with Toluene and the organic layer washed with water. Concentrated the total organic layer to obtain
wanted compound (Stage-2 Intermediate) as oil.
Stage-3 : A mixture of Stage-2 Intermediate, Acetic Anhydride and Triethyl Orthoformate was taken in to the
clean and dry reactor. Heated the reaction mass to 110° and maintained for 2hrs at the same temperature, then
concentrated the reaction mixture undre reduced pressure and dissolved in Methylene Dichloride. Added 2,4-
Difluoroaniline into the reaction mass. Maintained the reaction mass for 2hrs at 25-35°C and concentrated under
reduced pressure. Dissolved the residue in Diethyl Ether and washed the organic layer with Acetic acid followed
by water. Dried the organic layer and concentrated under reduced pressure. Dissolved the residue in
Tetrahydrofuran. Cooled the reaction mass to 0-5°C, slowly added Sodium Hydride into the reaction mass at 0-
5°C, then heated the reaction mass to refluxion. Maintained at the same temperature for 2hrs, cooled the
reaction mass to 10-15°C and slowly quenched with water, concentrated the reaction mass under reduced
pressure. Dissolved the residue in Methylene Dichloride, washed with water and concentrated to yield Stage-3
Compound.
Stage-4 : Taken Stage-3 Compound in to clean and dry reactor. Added Hydrochloric acid and Acetic acid to the
reaction mass. Heated the reaction mass to 100°C, maintained at the same temperature for 3hrs. Concentrated
and then obtained the residue. Crystallized the residue in Ethanol and water to yield Temafloxacin Hydrochloride.
87
ANNEXURE - IX
Flow Chart
1-(2,5-Difluoro-4-(3-
methylpiperzin-1-yl) phenyl)
ethanone Hydrochloride
Triethylamine Sol.Recovery
Di-tert-butyldicarbonate Evaporation Loss
Methylene Dichloride Stage I Effluent
Phosphoric acid Organic Residue
Sodium Bicarbonate Process Emissions
Sodium Chloride
Cyclohexane
Water
Stage-1
Diethyl Carbonate Sol.Recovery
Sodium Hydride (60%) Evaporation Loss
Stage II
Toluene Effluent
Acetic acid Organic Residue
Water Process Emissions
Stage-2
Triethyl Orthoformate
Acetic Anhydride
2,4-Difluoroaniline Sol.Recovery
Methylene Dichloride Evaporation Loss
Stage III
Diethyl Ether Effluent
Acetic acid Organic Residue
Tetrahydrofuran Process Emissions
Sodium Hydride (60%)
Water
Acetic acid Evaporation Loss
Hydrochloric acid (35%) Stage IV Effluent
Ethanol Organic Residue
Temafloxacin Hydrochloride
88
ANNEXURE - IX
PRODUCT : Trovafloxacin
Description :
Stage-1 : Tetrahydrofuran was taken in the reactor (M.C.0.1 below), added Sodium Borohydride and (1α,5α,6α)-
3-N-benzyl-6-nitro-2,4-dioxo-3-azabicyclo[3.1.0]hexane (take all safety precautions before charging Sodium
borohydride, Nitrogen blanket is maintained through out up to complex maintenance). Stirred the reaction mass
for 25mim under nitrogen atm at 25-30°C. Added boron trifluoride to reaction mass at below 40°C (It is highly
exothermic reaction). Maintained the reaction mass at 40°C for 4hrs. The reaction mass was checked for
completion then cooled to 25-30°C. Quenched the reaction mass with mixture of water and THF (1:1 ratio) and
maintained 30min at 45-50C. The reaction mass filtered to separate salt & extracted with Tetrahydrofuran.
Distilled the total organic layer under vacuum at 45-50°C to afford the wanted Stage-1 Compound as clear oil.
Stage-2 : Initially, Water and Isopropyl Alcohol was charged into the reactor & added Stage-1 Compound.
charged 10% Palladium Carbon to reaction mass, this reaction mixture hydrogenated 3.5 atm at 50°C for 24hrs.
Then the reaction mass was checked for completion and filtered the catalyst. Distilled the resulting filtrate under
reduced pressure to get and oil Stage-2 Compound.
Stage-3 : Toluene was used as a solvent. Initially solvent was taken into the reactor, Benzaldehyde and Stage-
2 material added. Then heated to 100-110°C. Maintained the reaction mass for 10hrs at 100-110°C by
removing water through azeotropically distillation mode. Distill out the solvent completely to obtain the wanted
Stage-3 Intermediate.
Stage-4 : Toluene was used as a solvent. Initially solvent was taken into the reactor, 7-Chloro-1-(2,4-
difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid and Stage-3 material added.
Then heated to 100-110°C. Maintained the reaction mass for 17hrs at 100-110°C. Cooled the reaction mass to
20-25°C. The Compound is then under goes reduction wtih Hydrogen in presence of Palladium Carbon to get
Trovafloxacin. The precipitated solid then re-crystallized the wet compound from Acetonitrile to obtain
Trovafloxacin as white solid.
89
ANNEXURE - IX
Flow Chart
(1R,5S,6R)-3-benzyl-6-nitro-3-
azabicyclo[3.1.0]hexane-2,4-
dione Sol.Recovery
Sodium Borohydride Evaporation Loss
Stage I
Tetrahydrofuran Effluent
Boran trifluoride Process Emissions
Tetrahydrofuran Complex
Water
Palladium Carbon Evaporation Loss
Isopropyl Alcohol Stage II Effluent
Hydrogen Organic Residue
Benzaldehyde Evaporation Loss
Stage III
Toluene Effluent
Organic Residue
Stage-3
7-Chloro-1-(2,4-difluorophenyl)-
6-fluoro-4-oxo-1,4-dihydro-1,8-
naphayridine-3-carboxylic acid Sol.Recovery
Triethylamine Evaporation Loss
Stage IV
Toluene Effluent
Palladium Carbon Process Emissions
Acetonitrile
Water
Trovafloxacin
90
ANNEXURE - IX
PRODUCT : Selegiline Hydrochloride
Description :
Stage-1 : N-Methyl-1-phenylpropane-2-amine-d-tartarate is suspended in water. The suspension is alkalized to

pH value of 13 by using Sodium Hydoxide solution at RT. The solution is extracted with Toluene. Raise the
temperature of organic layer to 60°C & add Propargyl Bromide, Sodium Hydoxide solution & water to RM at
60°C. Maintain RM for 2 hrs. & cool temperature to RT. Separate organic layer & add water, Acetic acid to
organic layer, so that the resulting aq layer has the pH 6-7, separate & dry organic layer. Concentrate half of
the amount to total quantity of Toluene. Acidify the organic layer at RT to get pH 1 by using Ethanolic
Hydrochloric acid. Filter the solid & dry at 60°C to get Selegiline Hydrochloride.
Flow Chart
N-Methyl-1-phenylpropane-2-
amine-d-tartarate
Propargyl Bromide
Sodium Hydroxide Sol.Recovery
Stage I
Toluene Effluent
Ethanolic Hydrochloric acid Organic Residue
(37%) Process Emission
Water
Selegiline Hydrochloride
91
ANNEXURE - IX
PRODUCT : Safinamide
Description :
Stage-1 : Toluene was taken in the reactor to which add 1-(Bromomethyl)-3-fluoro benzene and Potassium
Carbonate at room temperature, Maintain the reaction mixture for 10-15 minutes. Slowly charged 3-
(Bromoethyl) phenol at room temperature and stirred for 2-3 hours. After completion of the reaction, charged
water into reactor and separated two layers. Aqueous layer extract with Toluene and total organic layer washed
with water and organic layer is distilled off to give Stage-1 Product.
Stage-2 : Stage-1 Product and Methylene Dichloride was taken into a to the reactor. Added 2-
Aminopropanamide & Sodium Carbonate to the above mixture. Stirred the reaction mixture at room
temperature for 8-9 hours. After completion of the reaction, reaction mixture was washed with water. Organic
solvent is completely distilled off to obtained Safinamide.
Flow Chart
1-(Bromomethyl)-3-
fluorobenzene Sol.Recovery
3-(Bromomethyl) phenol Evaporation Loss
Stage I
2-Aminopropanamide Evaporation Loss
Sodium Carbonate Stage II Effluent
Methylene Dichloride Organic Residue
Safinamide
92
ANNEXURE - IX
PRODUCT : Landiolol
Description :
Stage-1 : Dimethyl Sulfoxide was charge in the reactor (M.C.0.1 below), Charge 3-(4-Hydroxyphenyl)
propanoic acid, after that Potassium Carbonate and Potassium Iodide were added, these mixture was
maintained for 10-20 minutes, Charged (S)-4-(Chloromethyl)-2,2-dimethyl-1,3-dioxolane the reaction mass
furher maintained for 10-12 hours. After that reaction mass was poured in to water, extracted the product with
Toluene. Distilled offf Toluene completely to get Stage-1 as a residue.
Stage-2 : Stage-1 and Acetone was charged in to a reactor, charged Potassium Carbonate and (S)-2-
(Bromomethyl) Oxirane and heat the reaction mass to 50-550C and stir the reaction mass at reflux for 10-13
hrs. After completion of the reaction filtered off, distilled off Acetone. Residue dissolved in Toluene and washed
with water. Distilled off Toluene completely to get Stage-2 Material .
Stage-3 : Methanol was charged in to a reactor and cooled to 15-200C, charged Stage-2 and N-(2-Aminoethyl)
morpholine-4-carboxamide. Stir the reaction mass at 15-200C for 13-15 hrs. After completion of the reaction.
Distilled off Methanol completely. And then washed with water. Landiolol pharma Product was recrystallized
with Ethyl Acetate.
93
ANNEXURE - IX
PRODUCT : Landiolol
Flow Chart
3-(4-Hydroxyphenyl)propanoic
acid
(S)-4-(Chloromethyl)-2,2- Sol.Recovery
dimethyl-1,3-dioxolane Evaporation Loss
Potassium Carbonate Stage I Effluent
Potassium Iodide Organic Residue
Dimethyl Sulfoxide Process Emissions
Toluene
Water
Stage-1
(S)-2-(Bromomethyl) oxirane Sol.Recovery
Stage II
Acetone Effluent
Stage-2
N-(2-Aminoethyl)morpholine-4- Sol.Recovery
carboxamide Evaporation Loss
Stage III
Methanol Effluent
Ethyl Acetate Organic Residue
Water
Landiolol
94
ANNEXURE - IX
PRODUCT : Sitagliptin Hydrochloride
Description :
Stage-1 : 2,4,5-Trifluoro benzyl-α-amino acid is reacted with Diazomethane in presence of Isobutyl

Chloroformate, silver benzoate and Carbobenzyloxy chloride base and methanol solvent to get 2,4,5-Trifluoro
benzyl-β-amino acid.
Stage-2 : 2-Chloropyrazine is reacted with Hydrazine Hydrate in presence of Methanol to form 2-Hydrazine
pyrazine.
Stage-3 : 2-Hydrazine pyrazine is reacted with Triethyl orthoester and polyphosphoric acid in presence of
Methanol to get 3-Trifluoromethyl[1,2,4]triazolo[4,3-a]pyrazine.
Stage-4 : 3-Trifluoromethyl[1,2,4]triazolo[4,3-a]pyrazine is reacted with reduction of Palladium Carbon,

Hydrogen in presence of Methanol solvent and salt formation with Hydrochloric acid to form 3-Trifluoromethyl-
5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine Hydrochloride.
Stage-5 : 2,4,5-Trifluoro benzyl-β-amino acid and 3-Trifluoromethyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-

a]pyrazine Hydrochloride with Dimethyl Formamide other peptide coupling to get Amino protection of
Sitagliptin.
Stage-6 : Amino protection of sitagliptin is deprotection with Methanolic Hydrochloride in presence of

Methanol solvent for carbo benzyloxy chloride to get Sitagliptin Hydrochloride.
95
ANNEXURE - IX
Flow Chart
2,4,5-Trifluorobenzyl-a-amino
acid
Isobutyl Chloroformate Sol.Recovery
Silver benzoate Evaporation Loss
Stage I
Carbo benzyloxychloride Process Emissions
Diazomethane in Diethyl ether
(40%)
2-Chloro Pyrazine Sol.Recovery

Hydrazine Hydrate Evaporation Loss
Stage II
Process Emissions
Triethyl orthoester Evaporation Loss
Stage III
Polyphosphoric Acid Organic Residue
Stage-3
Palladium Carbon Sol.Recovery
Hydrogen Stage IV Evaporation Loss
Hydrogen Chloride Process Emissions
Stage-4 Stage V Evaporation Loss
Dimethylformamide Organic Residue
Methanol Evaporation Loss
Stage VI
Methanolic Hydrochloride Organic Residue
(20%) Process Emissions
Sitagliptin Hydrochloride
96
ANNEXURE - IX
PRODUCT : Perindopril Erbumine
Description :
Stage-1 : Indole carboxylic acid is reacts with Rhodium on carbon under Hydrogen pressure in Methanol
solvent media to get Stage-1 intermediate.
Stage-2 : Stage-1 intermediate is reacts with Benzyl alcohol and 1,3-Dicyclohexyl carbodiimide in Toluene
Stage-3 : Stage-2 intermediate is reacts with Mandelic Acid in the presence of Potassium Carbonate in
Toluene solvent media to get Stage-3 intermediate.
Stage-4 : Norvaline is reacts with Ethanol in the presence of Sulfuric acid in Toluene and Acetone solvent
media to get Stage-4 intemediate.
Stage-5 : Stage-4 intemediate is reacts with Pyruvic Acid under Hydrogen pressure in the presence of
Palladium Carbon in Methanol and Toluene solvent media to get Stage-5 intermediate.
Stage-6 : Stage-5 intermediate is reacts with Stage-3 intermediate and 1,3-Dicyclohexyl carbodiimide in
Toluene and Methanol solvent media to get Stage-6 intermediate.
Stage-7 : Stage-6 intermediate is tert-Butylamine under Hydrogen pressure in the presence of Palladium
Carbon in Toluene and Methanol solvent media to get Perindopril Erbumine.
97
ANNEXURE - IX

Flow Chart
Indole carboxylic acid Sol.Recovery
Rhodium on Carbon Evaporation Loss
Hydrogen Stage I Organic Residue
Stage-1
Benzyl Alcohol Sol.Recovery
1,3-Dicyclohexyl carbodiimide Stage II Evaporation Loss
Toluene Effluent
Stage-2
Mandelic Acid Sol.Recovery
Acetone Evaporation Loss
Stage III
Norvaline
Ethanol Sol.Recovery
Sulfuric Acid Evaporation Loss
Stage IV
Toluene Effluent
Water
Stage-4
Hydrogen Evaporation Loss
Toluene Stage V Effluent
Pyruvic Acid Process Emissions
Water
Stage-3
1,3-Dicyclohexylcarbodiimide Evaporation Loss
Stage VI
Toluene Effluent
Water
Stage-6
Toluene Effluent
Methanol Stage VII Organic Residue
tert-Butylamine Inorganic Solid Waste
Carbon Spent Carbon
Water
Perindopril Erbumine
98
ANNEXURE - IX
PRODUCT : Cangrelor
Description :
Stage-1: A suspension of sodium hydroxide and 2-(Acetoxyethyl)-5-(6-chloro-2-mercapto-9H-purin-9-yl)-tetra-

hydrofuran 3,4-diyl diacetate in dimethylformamide was stirred at room temperature for 1 hour. To this slowly
added 3-chloro-1,1,1-trifluoropropane at the same temperature. The reaction mixture was stirred for 5 days.
After completion of the reaction the solution was concentrated to residue and the residue partitioned between
ethyl acetate and water. The organic layer was distilled off to obtain the product.
Stage-2: Stage-1 product and 2-(methylthio)ethanamine were mixed in dioxane and water and heated to 110°C
in an autoclave for 20 hrs. After completion of the reaction, reaction mass was cooled to room temperature and
evaporated to a residue. The residue was recrystallised from ethylacetate to yield Stage-2 product.
Stage-3: Phosphorus oxychloride was added drop wise with cooling to a solution of the product of stage-2 in
triethyl phosphate. The resulting solution was stirred at room temperature for 3 hours. Added a solution of
tributylamine and dichloromethylenebisphosphonic acid in triethyl phosphate to the above reaction mixture at
room temperature and stirred the reaction mixture till the completion of the reaction. Reaction mixture was
poured into a 5% aqueous sodium bicarbonate solution then stirred for 18 hrs. The resulting solution was
extracted with ethyl acetate. Cooled the ethyl acetate layer to -5-10°C. Precipitated solid was filtered to obtain
the product.
99
ANNEXURE - IX
PRODUCT : Cangrelor
Flow Chart
2-(Acetoxyethyl)-5-(6-chloro-2-
mercapto-9H-purin-9-yl)
tetrahydrofuran-3,4-diyl Sol.Recovery
diacetate Evaporation Loss
Sodium Hydroxide Effluent
Stage I
3-Chloro-1,1,1-trifluoro propane Organic Residue
Dimethylformamide Inorganic Solid Waste
Sodium Sulfate
Water
2-(Methylthio) ethanamine Evaporation Loss
1,4-Dioxane Stage II Effluent
Stage-2
Triethyl Phosphate
Dichloromethylene Sol.Recovery
diphosphonic acid Evaporation Loss
Tributylamines Stage III Effluent
Phosphorous Oxychloride Organic Residue
Sodium Bicarbonate
Isopropyl Alcohol Process Emissions
Water
Cangrelor
100
ANNEXURE - IX
PRODUCT : Cilomilast
Description :
Stage-1: Charge dichloromethane in to a reactor and cool to 0-5°C and then added oxycyclohexane
carbonitrile. Stirred the reaction mixture for 1-2 hours. Slowly added 1,3-dithian-2-one and titanium tetrachloride
to the above mixture and then compound diluted with dichloromethane. Stirred the reaction mixture at 0-5C for
5-6 hours. After completion of the reaction, quench the reaction mixture with ammonium chloride solution and
extract the product with dichloromethane. Distilled off dichloromethane layer and isolate the product.
Stage-2: Charge methanol in to a reactor and then added stage-1 product, sodium hydroxide solution and zinc
chloride. Heat the reaction mixture to 40-45°C and stirred the reaction mixture for 5-6 hours at the same
temperature. After completion of the reaction. Charge water to the reaction mixture. Filtered the precipitated
solid and then dried to get Cilomilast.
Flow Chart
1-( 3-(Cyclopentyloxy)-4-
methoxyphenyl)-4- Sol.Recovery
oxocyclohexane carbonitrile Evaporation Loss
Titanium Tetrachloride Effluent
Stage I
1,3-Dithian-2-one Organic Residue
Methylene Dichloride Inorganic Solid waste
0
Stage-1
Methanol Stage II Evaporation Loss
Zinc Chloride Effluent
Cilomilast
101
ANNEXURE - IX
PRODUCT : Sitafloxacin
Description :
Stage-1: 8-chloro-6,7-difluoro-1-((1S,2S)-2-fluorocyclopropyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

reacts with (S)-tert-butyl 5-azaspiro[2.4]heptan-7-ylcarbamate in the presence of acetonitrile and triethylamine.
Heated the reaction mixture to reflux and maintain the reaction at reflux for 5 hrs. After completion of the
reaction, cooled the reaction mixture and filtered the reaction mixture. Wash the organic layer with water and
distilled off the solvent completely to obtain the product as residue.
Stage-2 : Stage-1 and anisole taken in a reactor and cooled to 0-5°C. Slowly trifluoroacetic acid added
between 0-5°C. Raised the reaction mixture temperature to 25-30°C and maintained for 30 min at the same
temperature. After completion of the reaction, distilled off solvent completely under vacuum below 60°C. Then
cool to 25-30°C and adjust the reaction mass pH with 1N sodium hydroxide solution to 11 to 12. Wash the
reaction mixture with chloroform. Adjust the reaction mass pH with hydrochloric acid to 7.0. Extracted with
chloroform and dried over sodium sulphate. Distilled off solvent under vacuum at below 50°C and isolated in
Ethanol to form Sitafloxacin.
102
ANNEXURE - IX
Flow Chart
8-Chloro-6,7-difluoro-1-
((1S,2S)-2-fluorocycloproyl)-4-
oxo-1,4-dihydroquinoline-3-
carboxylic acid Sol.Recovery
Stage I
(S)-tert-Butyl-5-azaspiro[2,4]- Evaporation Loss
heptan-7-yl-carbamate Organic Residue
Acetonitrile
Triethylamine
Stage-1
Anisole
Trifluoroacetic acid Sol.Recovery
Sodium Hydroxide Evaporation Loss
Hydrochloric acid (35%) Stage II Effluent
Chloroform Organic Residue
Sodium Sulfate Inorganic Solid Waste
Ethanol Process Emission
Water
Sitafloxacin
103
ANNEXURE - IX
PRODUCT : Formoterol Fumarate
Description :
Stage-1 : Methanol was used as a solvent. Initially, Methanol was taken in the reactor (M.C.0.1 below),charge
N-(2-(benzyloxy)-5-(oxiran-2-yl)phenyl)formamide, (take all safety precautions before charging Sodium
borohydride, Nitrogen blanket is maintained through out) after that methanol and sodium hydroxide flakes,
these mixture was maintained another 5-10 minutes, and charged N-benzyl-1-(4-methoxyphenyl) propan-2-
amine. Strirred the the reaction mass for 4-5 hours, checked for completion of reaction. Distilled offf methanol
completely.Charged fresh methanol to the reaction mass and filtered off the Stage-1 product.
Stage-2 : Methanol and palladium carbon was charged in to a reactor, charged Stage1 product.Passed
hydogen gas and heated to 35-450C, after completion of reaction cooled to 25-30C and filtered off. Distilled of
filtrate and isolated Stage-2 product.
Stage-3 : Methanol was charged in to a reactor and charged stage 2 product, fumaricacid and heat to 45-
55oC.Stir the the reaction mass for 1-2 hours. Cool to 5-10oC and stir for 2-3 hours. Filted off the Foromterol
Fumarate. Dry the product at 50-60oC for 6-8 hors.
Flow Chart
N-(2-(benzyloxy)-5-(oxiran-2-
yl)phenyl) formamide
N-benzyl-1-(4- Sol.Recovery
methoxyphenyl)propan-2- Stage I Evaporation Loss
amine Organic Residue
Sodium Hydroxide Inorganic Solid Waste
Methanol
Stage II
Palladium Carbon Process Emissions
Fumaric acid Stage III Evaporation Loss
Formoterol Fumarate
104
ANNEXURE - IX
PRODUCT : Clevidipine Butyrate
Description :
Stage-1 : Isopropyl alcohol is used as a solvent for the reaction. Isopropanol is charged into the reactor. Then
charged 2,3-dichlorobenzaldehyde. After 5 – 10min ammonium acetate will be charged under nitrogen
atmosphere. The reaction mass will be stirred for 5 – 10min at RT. Then methyl acetoacetate will be charged.
Reaction mass is heated to 80 – 85°C and maintained at 80 – 85°C for 8 – 10hours. The reaction mass is
checked for completion of the reaction. After completion of the reaction the reaction mass will be cooled to RT
and further cooled to 5 – 10°C. The separated solid is centrifuged and washed with chilled isopropyl alcohol to
form Stage-1 compound.
Stage-2 : Initially, isopropyl alcohol and water was charged into the reactor & added stage-I material, heated up
to reflux and maintained at reflux for 18-20hours. The mass was checked for completion of reaction. Then
solvent isopropanol can be removed completely. The reaction mass is washed with toluene and after that acetic
acid was used to adjust pH 4.0 - 4.5 of reaction mass. Then centrifuged the mass to collect the material of
crude stage II. This material is is charged into the reactor. Acetone is charged and heated the reaction mass to
reflux. The reaction mass is maintained at reflux for 30 – 60min. Cooled the reaction mass to RT and further
cooled to 0 – 5°C. The mass was centrifuged to obtain the Stage 2 material.
Stage-3 : DMF is used as a solvent. Initially solvent was taken into the reactor, NaHCO3 and stage-2 material
added. Then heated to 80-85oC. Reaction mass was maintained 4 - 6hrs at 80 – 85oC. Completion of the
reaction mass checked. After completion of the reaction the reaction mass will be filtered and further distilled
the solvent completely. Crude is dissolved in ethyl acetate and distilled off ethyl acetate completely. The crude
compound is dissolved in methanol at 60 – 65°C and cooled to RT. The reaction mass is further
cooled to 10 – 15°C. The mass was centrifuged to obtain Clevidipine Butyrate.
105
ANNEXURE - IX
Flow Chart
2,3-Dichlorobenzaldehyde
Methyl Acetoacetate Sol.Recovery
Stage I
Ammonium Acetate Evaporation Loss
Stage-1
Potassium Hydroxide
Acetic acid Sol.Recovery
Isopropyl Alcohol Stage II Evaporation Loss
Toluene Effluent
Water
Stage-2
Dimethylformamide Sol.Recovery
Sodium Bicarbonate Evaporation Loss
Stage III
Chloromethyl Butyrate Organic Residue
Ethyl Acetate Inorganic Solid Waste
Methanol Process Emissions
Clevidipine Butyrate
106
ANNEXURE - IX
PRODUCT : Udenafil
Description :
Stage-1: Acetone was taken in the reactor to which 2-(1-methylpyrrolidin-2-yl)ethanamine is added at room
temperature. After that 5-(chlorosulfonyl)-2-propoxybenzoic acid in acetone was added at 0°C and the mixture
was stirred below 20°C for 3 hours till the completion of the reaction.. After that removed the solvent by
concentration. The residue obtained was diluted with ethyl acetate and extracted with 10% sodium bicarbonate
solution. Acidified the aqueous layer with hydrochloric acid and then extracted with ethyl acetate. Ethyl acetate
layer is washed with water and distilled off to get as crude compound.
Stage-2: Crude compound obtained in stage-1 was dissolved in dichloromethane and the reaction mixture is
cooled to 0°C and to this added triethyl amine and 2,4,6-trichlorobenzoyl chloride at 0°C. The reaction mixture
is stirred at room temperature for 5 hours. Added 4-amino-1-methyl-3-propyl-1H-pyrazole-5-carboxamide to the
reaction mixture and the resulting mixture is stirred at room temperature for 3 hours. Reaction mixture is
checked for the completion of the reaction. The precipitated crystals were centrifuged. The filtrate is washed
with saturated sodium bicarbonate solution and dichloromethane layer is concentrated to get pure compound
as a residue.
Stage-3: Stage-2 crude is dissolved in t-butanol. This solution is added with potassium tertiary butoxide. The
reaction mixture was heated to reflux for 20 hours. The reaction mass is checked for its completion. The
reaction mixture was allowed to cool to room temperature. Water was added to the mixture, and pH of the
reaction mass is adjusted to 2. The resulting solid was centrifuged and washed with water. The wet solid is
dissolved in isopropanol at reflux. Cooled the reaction mass to room temperature stirred the reaction mass for 2
hours at room temperature. The solid is centrifuged and dried to get Udenafil
107
ANNEXURE - IX
PRODUCT : Udenafil
Flow Chart
5-(Chlorosulfonyl)-2-
propoxybenzoic acid
2-(1-Methylpyrrolidin-2-yl) Sol.Recovery
ethanamine Evaporation Loss
Acetone Stage I Effluent
Hydrochloric acid (35%)
Water
Stage-1
4-Amino-1-methyl-3-propyl-1H-
pyrazole-5-carboxamide Sol.Recovery
Stage II Effluent
2,4,6-Trichlorobenzoyl chloride
Metthylene Dichloride Organic Residue
Water
Stage-2
Potassium tert-butoxide Sol.Recovery
tert-Butanol Evaporation Loss
Stage III
Hydrochloric acid (35%) Effluent
Water
Udenafil
108
ANNEXURE - IX
PRODUCT : Argatroban
Description :
Stage-1: To a stirred solution of 2-[(tert-butoxycarbonyl)amino]-5-(nitro carbamimidamido) pentanoic acid in dry

tetrahydrofuran were added triethyl amine and isobutylchloroformate at -20°C. After 10 min a solution of Ethyl
(2R,4R)-4-methyl piperidine-2-carboxylate in tetrahydrofuran was added at the same temperature Stirred the
reaction mixture for 3 hours. After completion of reaction the reaction mixture was concentrated and dissolved
in ethyl acetate. The organic layer was washed with sodium bicarbonate solution, citric acid solution and brine
successively. The organic layer was concentrated and dried to yield a syrupy mass.
Stage-2: A solution of Stage-1 in ethyl acetate was cooled to 0°C and then a solution of dry hydrochloric acid
and ethyl acetate was added to it. The reaction mixture was stirred for 4 hours at room temperature. After
completion of the reaction. diethylether was added to precipitate an oily residue. The solid obtained was filtered
and washed with diethylether to form solid.
Stage-3: To a solution of Stage-2 in chloroform were added triethylamine and 3-ethyl-8-quinolinesulfonyl

chloride at 5°C. Rise the temperature of reaction mixture to room temperature and stirring reaction at the same
temperature. After completion of the reaction, the reaction mixture was washed with water and brine solution.
Distilled off the organic layer completely to yield compound as an amorphous solid.
Stage-4: To the compound obtained in stage-3 was dissolved in ethanol and added 5% palladium charcoal to
it. The reaction mass was hydrogenated in an autoclave for 4 hours. After completion of the reaction, filtered
the reaction mixture through a cilite bed. To the filtrate added 1N sodium hydroxide and stirred for 4 hours. The
reaction mixture was acidified with concentrated hydrochloric acid and the solid precipitated was filtered. The
crude Argatroban was recrystallized from ethyl acetate.
109
ANNEXURE - IX
Flow Chart
2-[(tert-Butoxycarbonyl)amino] -
5-(nitrocarbamimidamido)
pentanoic acid
Ethyl(2R,4R)-4-methyl
piperidine-2-carboxylate Sol.Recovery
Isobutyl chloroformate Stage I Effluent
Tetrahydrofuran Organic Residue
Citric acid
Sodium Bicarbonate
Sodium Chloride
Water
Ethyl Acetate Evaporation Loss
Diethyl Ether Organic Residue
Stage-2
Ttetrahydroquinoline-8-sulfonyl
chloriode Sol.Recovery
Triethylamine Stage III Evaporation Loss
Chloroform Effluent
Sodium Chloride Organic Residue
Water
Stage-3
Palladium Carbon
Hydrogen gas Sol.Recovery
Sodium Hydroxide (20%) Evaporation Loss
Stage IV
Ethanol Organic Residue
Water
Argatroban
110
ANNEXURE - IX
PRODUCT : Balofloxacin
Description :
Stage-1 : A mixture of 1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylic acid,

methylaminopiperidine dihydrochloride and acetonitrile were taken in a reactor. To this triethylamine was
added. Heat the reaction mixture to refluxed with stirring and maintain for 12 hours till the completion of the of
the reaction. Then reaction mixture was concentrated in vacuum, and the residue was extracted with chloroform
and water. The extract was washed with saturated sodium chloride solution and concentrated the organic layer
under vacuum to obtain Balofloxacin, which was recrystallized in acetonitrile-water.
Flow Chart
1-Cyclopropyl-6,7-difluoro-8-
methoxy-4-oxo-1,4-dihydro
quinolin-3-carboxylic acid
N-Methylpiperidine-3-amine Sol.Recovery
Dihydrochloride Evaporation Loss
Stage I
Triethylamine Effluent
Acetonitrile Organic Residue
Chloroform
Sodium Chloride
Water
Balofloxacin
111
ANNEXURE - IX
PRODUCT : Beraprost
Description :
Stage-1: Sodium hydride was suspended in dimethoxy ethane under nitrogen atmosphere and to this added a
solution of dimethyl-(3-methyl-2-oxo-hept-5-yn-1-yl)phosphate in dimethylformamide. The reaction mixture was
stirred for 1 hour at room temperature. A solution of methyl-4-(2-acetoxy-1-formyl-2,3,3a,8b-tetrahydro-1H-
benzo [b]cyclopenta[d]furan-5-yl)butanoate in dimethoxyethane was prepared and added to the above reaction
mixture, and the reaction mixture was stirred for another 30 minutes at room temperature. After completion of
the reaction, the reaction mixture was neutralized with acetic acid and was concentrated. The residue was
dissolved in (1:1) pentane and ether, and the precipitate was filtered. The filtrate was concentrated to give an
oily material.
Stage-2: The compound obtained in stage-1 was dissolved in methanol and to this added a 10% sodium
hydroxide solution at 0°C. The reaction mixture was stirred for 14 hrs at room temperature. After completion of
the reaction, the reaction mixture was neutralized with 10% aqueous hydrochloric acid, and the crude
compound precipitated was filtered and dried at 45°C.
Stage-3: The crude compound obtained in the Stage-2 was dissolved in methanol and cooled to 0°C. Then
sodium borohydride was added to it in portion wise over a period of 2 hrs and stirred the reaction mixture at
room temperature for 2 hours. After completion of the reaction, the reaction mass was neutralized with 10%
aqueous hydrochloric acid. and the precipitate formed was filtered and recrystallized from ethyl acetate to get
the final product.
112
ANNEXURE - IX
PRODUCT : Beraprost
Flow Chart
Methyl-4-(2-acetoxy-1-formyl-
2,3,3a,8b-tetrahydro-1H-
benzo[b]cyclopenta[d]furan-5-
yl)butanoate
Dimethyl(3-methyl-2-oxo-hept- Sol.Recovery
5-yn-1-yl)phosphate Evaporation Loss
Sodium Hydride (60%) Stage I Effluent
Dimethoxyethane Organic Residue
Dimethylformamide Process Emissions
Pentane
Diisopropyl Ether
Acetic acid
Water
Stage-1
Sodium Hydroxide (10%) Sol.Recovery
Hydrochloric acid (35%) Stage II Evaporation Loss
Methanol Effluent
Water
Stage-2
Sodium Borohydride Sol.Recovery
Hydrochloric acid (35%) Evaporation Loss
Stage III
Methanol Effluent
Beraprost
113
ANNEXURE - IX
PRODUCT : Pazufloxacin
Description :
Stage-1: Ethyl-3-(4-(1-acetamidocyclopropyl)-2,3,5-trifluorophenyl)-3-oxopropanoate and chloroform taken in a

reactor. Charged N,N dimethyl formamide dimethyl acetal and acetic anhydride to the above mixture.
Maintained the reaction mixture at 25-30°C for 2 hrs. After completion of the reaction, distilled off solvent
completely under vacuum below 50°C. The obtained residue dissolved in chloroform and slowly added S-
(2)aminopropanol and maintained for 2 hrs. After completion of the reaction, distilled off solvent under vacuum
at below 50°C to obtained the product.
Stage-2: Crude product obtained in Stage-1 and DMSO taken in a reactor and added potassium carbonate.
Heated the reaction mixture to 90-95°C and maintain the reaction at the same temperature. After completion of
the reaction, the reaction mixture was dumped by pouring the reaction mixture into ice water and chloroform.
Reaction mixture pH adjusted to 2 with 6N hydrochloric acid solution. The organic layer was distilled completely
under vacuum at below 50°C. The obtained compound proceeded to next stage.
Stage-3: Compound obtained in stage-2 and ethanol taken in a reactor. 1N sodium hydroxide solution was
added to the reaction mixture at 25-30°C. Rise the temperature of the reaction to 45-50°C and the maintained
for 2 hrs. After completion of the reaction, cool the reaction mixture to 25-30°C and adjust the reaction mixture
pH with 6N hydrochloric acid solution. Filter the compound and wash with water. Dry the compound at 80-90°C
to get the product.
Stage-4 : Stage-3 and 6N hydrochloric acid solution taken in a reactor and heat to 70-75°C and maintained the
reaction mixture at the same temperature for 20 hrs. After completion of the reaction, distilled off the reaction
mixture under vacuum at below 60°C. The obtained residue dissolved in water, potassium hydroxide and
ethanol. Stirred the reaction mass at 25-30°C. Filtered the reaction mixture and washed with water, Dry the
obtained Pazufloxacin at 60-70°C.
114
ANNEXURE - IX
Flow Chart
Ethyl-3-(4-(1-acetamido cyclo
propyl)-2,3,5-trifluorophenyl)-3-
oxopropanoate Sol.Recovery
N,N-Dimethylformamide Evaporation Loss
Stage I
Acetic anhydride Organic Residue
S-(2)-Aminopropanol Process Emissions
Chloroform
Ethanol
Stage-1
Potassium Carbonate Sol.Recovery
Dimethyl Sulfoxide Evaporation Loss
Stage II
Chloroform Effluent
Hydrochloric acid (22%) Organic Residue
Water
Stage-2
Sodium Hydroxide (45%) Sol.Recovery
Ethanol Stage III Evaporation Loss
Water Oganic Residue
Stage-3
Hydrochloric acid (22%) Sol.Recovery
Potassium Hydroxide Stage IV Evaporation Loss
Ethanol Effluent
Pazufloxacin
115
ANNEXURE - IX
PRODUCT : Talipexole
Description :
Stage-1 : Toluene was used as as solvent ,initially toluene was taken in the reactor to which add azepan-4-
oneand potassium carbonate at RT, Maintain the R.M10-15 mints ,slowly addition of 3-chloro propan-1-ene at
RT,after that maintained for 2-3 hrs the reaction mass was checked for completion of reaction,charged water
into reactor ,separated two layers ,to aq layer extract with toluene .total organic layer washed with water ,dry
with sodium sulphate and concentrate organic layer.
Stage-2 : DCM used as a solvent initially solvent taken into a to the reactor stage -1 and bromine & acetic acid
,thio urea added then maintained at RT 8-9 hrs check TLC if TLC completed ,the reaction mass adjust PH 10
with sodium hydroxide solution the mixture was extract with DCM ,organic layer dry with sodium sulphate and
evaporated we have been obtained Talepexole.
Flow Chart
Azapane-4-one Sol.Recovery
3-Chloropropan-1-ene Evaporation Loss
Potassium Carbonate Stage I Effluent
Stage-1
Bromine
Thiourea Sol.Recovery
Acetic acid Stage II Evaporation Loss
Water
Talipexole
116
ANNEXURE - IX
PRODUCT : Almotriptan
Description :
Stage-1 : The Stage-1 involves the condensaion of 4-Nitrobenzyl bromide with Sodium Sulfite in water to give
4-Nitrobenzene methane sulfonic acid sodium salt.
Stage-2 : This stage comprises conversion of 4-Nitrobenzene methane sulfonic acid sodium salt into sulfonyl
chloride using Phosphorus Oxychloride in presence of Toluene. The 4-Nitrobenzene methane sulfonyl chloride
obtained is treated with Pyrrolidine to yield 4-(1-Pyrrolidino sulfonyl methyl) nitrobenzene.
Stage-3 : Stage-2 material is treated with Hydrazine Hydrate in Methanol using Ferric chloride as catalyst
where Nitro group is reduced to get 4-(1-Pyrrolidino sulfonyl methyl) benzene amine.
Stage-4 : 4-(1-Pyrrolidino sulfonyl methyl) benzene amine is diazotised with Sodium Nitrite and Hydrochloric
acid and the resulting diazonium salt is reduced with Stannous Chloride dihydrate and Hydrochloric acid to give
4-Pyrrolidino sulfonyl methyl phenyl hydrazine Hydrochloride.
Stage-5 : Stage-5 is the condensation of Stage-4 with 4-Chlorobutyraldehyde Sodium Bisulfite adduct to give 3-
(2-Aminoethyl)-5-(1-pyrrolidinyl) sulfonyl methyl indole.
Stage-6 : Amino methyl derivatis obtained in stage-5 is treated with Formaldehyde solution using Sodium
Borohydride to give Almotriptan.
117
ANNEXURE - IX
Flow Chart
4-Nitrobenzyl bromide
Sodium Sulfite Stage I Effluent
Water
Phosphorous Oxychloride Evaporation Loss
Toluene Stage II Effluent
Pyrrolidine Organic Residue
Hydrazine Hydrate (50%) Effluent
Carbon Stage III Organic Residue
Toluene Inorganic Solid Waste
Water Spent Carbon
Ferric Chloride Process Emissions
Stage-3
Sodium Nitrite Sol.Recovery
Stage IV
Stannous Chloride dihydrate Evaporation Loss
Isopropyl Alcohol Effluent
Water
Stage-4
4-Chlorobutyraldehyde Sodium
Bisulfite adduct Sol.Recovery
Isopropyl Alcohol Evaporation Loss
Water Effluent
Stage V
Hyflo Organic Residue
Disodium Hydrogen Phosphate Inorganic Solid Waste
Vaccum Salt Process Emissions
Sodium Hydroxide
Methylene Dichloride
Stage-5
Methanol Sol.Recovery
Formaldehyde (35%) Evaporation Loss
Stage VI
Ethyl Acetate Effluent
Sodium Borohydride Organic Residue
Water
Almotriptan
118
ANNEXURE - IX
PRODUCT : Rizatriptan Benzoate
Description :
Stage-1 : 4-Ntrobenzyl bromide is condensed with 4-Amino-1,2,4-triazole in presence of Isopropyl Alchol to

give 1-(4-Nitrobenzyl)-4-amino-1,2,4 triazolium bromide.
Stage-2 : 1-(4-Nitrobenzyl)-4-amino-1,2,4 triazolium bromide is treated with Sodium Nitrite and Hydrochloric
acid to give 1-(1,2,4-Triazol-1-yl methyl)-4-nitrobenzene.
Stage-3 : The Nitro derivatives obtained form Stage-2 is reduced by using Hydrazine Hydrate in Methanol and
Ferric Chloride is used as catalyst to give 4-(1H-1,2,4-Triazol-1-yl methyl) aminobenzene.
Stage-4 : 4-(1H-1,2,4-Triazol-1-yl methyl) aminobenzene is diazotised using Sodium Nitrite and Hydrochloric
acid and the resulting diazonium chloride solution is reduced with Stannous Chloride Dihydrate and
Hdyrochloric acid to give 4-(1H-1,2,4-Triazol-1-yl-methyl) phenylhydrazine Hydrochloride.
Stage-5 : 4-(1H-1,2,4-Triazol-1-yl-methyl) phenylhydrazine Hydrochloride prepared in Stage-4 is condensed

with (4,4-Diethoxy butyl) dimethylamine in Sulfuric acid solution to give Rizatriptan base.
Stage-6 : Rizatriptan base is treated with Benzoic acid in Acetone media to give Rizatriptan Benzoate.
119
ANNEXURE - IX
Flow Chart
4-Nitrobenzyl bromide Sol.Recovery
4-Amino-1,2,4-Triazole Stage I Evaporation Loss
Stage-1
Sodium Nitrite
Hydrochloric Acid (35%) Stage II Effluent
Ammonia Solution (20%) Process Emissions
Water
Stage-2
Ferric Chloride Evaporation Loss
Hydrazine Hydrate (50%) Effluent
Stage III
Carbon Organic Residue
Toluene Inorganic Solid Waste
Methylene Dichloride Spent Carbon
Stage-3
Stannous Chloride Dihydrate
Sodium Nitrite
Hydrochloric Acid (35%) Sol.Recovery
Methylene Dichloride Stage IV Evaporation Loss
Vaccum Salt Effluent
Ammonia Solution (20%)
Isopropyl Alcohol
Water
(4-4-Diethoxybutyl) Evaporation Loss
dimethylamine
Stage V
Methylene Dichloride Effluent
Sulfuric Acid
Rizatriptan Sol.Recovery
Benzoic Acid Stage VI Evaporation Loss
Rizatriptan Benzoate
120
ANNEXURE - IX
PRODUCT : Imipenem
Description :
Stage-1 : Mixture of Dichloromethane and N.N-dimethylformamide was used as a solvent. Initially,
Dichloromethane and N.N-dtmethylacetamide was taken in the reactor , to which 4-nitrobenzyl 6-(1-
hydroxyethyl)-3,7-dioxobicyclo[3.2.0]heptane-2-carboxylate added at RT,Then cooled to -55 to-60oC, 4-
(dimethylamino)pyridine and Diisoproylethylamine added.Diphenylchlorophosphate in Dichloromethane added
slowly at -55 to-60oC, after that maintained for 30min at same temparature. Reaction mass quenched into
water, Seperated the layers and aqueous layer extracted with DCM. Concentrated mass under reduced
pressure and centrifuged the mass. Distilled the filtrate under reduced pressure.
Stage-2 : Mixture of Dichloromethane and N.N-dimethylacetamide was used as a solvent. Initially,
Dichloromethane and N.N-dtmethylacetamide was taken in the reactor , to which 4-nitrobenzyl 3-
(diphenoxyphosphoryloxy)-6-(1-hydroxyethyl)-7-oxobicyclo[3.2.0]hept-2-ene-2-carboxylate added at RT,then
cooled to -55 to-60oC and added Diisoproylethylamine. The reaction mass further cooled to -70 to -75oC and
added 2-aminoethanethiol hydrochloride in N.N-dimethylacetamide during 10 min, after that maintained for
60min and added mixture of Diisoproylethylamine and Benzyl formimidate hydrochloride. Maintained for 60min
then reaction mass quenched into water and adjusted the pH to 7.0-7.5 with sodium hydroxide solution.
Seperated the layers and aqueous layer extracted with DCM. Concentrated mass under reduced pressure and
centrifuged the mass. Distilled the filtrate under reduced pressure.
Stage-3 : Initially, isopropylalcohol was charged into the reactor then added stage-I material and pd/C.
Hydrogenated at 3-4Kg pressure for 2.5 hour. Filtered the pd/C ,distilled the solvent up to 70%. Cooled the
reaction mass to 5-10°C and maintained for 2hrs. Centrifuged the mass collect the material of Imipenem.
121
ANNEXURE - IX
PRODUCT : Imipenem
Flow Chart
4-Nitrobenzyl-6-(1-hydroxy
ethyl)-3,7-dioxoazabicyclo
[3.2.0]heptane-2-carboxylate
Sol.Recovery
Diphenyl chlorophosphate Evaporation Loss
Stage I
4-(Dimethylamino) pyridine Effluent
Diisopropylamine Organic Residue
Dimethylformamide
Water
Stage-1
Diisopropylamine
2-Aminoethanethiol
Hydrochloride
Benzylformimidate Sol.Recovery
Hydrochloride Stage II Evaporation Loss
N,N-Dimethylacetamide
Heptane
Water
Stage III
Palladium Carbon Organic Residue
Hydrogen Process Emissions
Imipenem
122
ANNEXURE - IX
PRODUCT : Cefixime
Description :
Stage-1: Thiourea and water were taken in the reactor and cooled to 10-15°C. Sodium acetate was added at
10-15°C. After that (Z)-4-chloro-2-[[(2-ethoxycarbonyl)methoxy] imino]-acetoacetic acid was added at 10-15°C.
Rise the temperature to 25-35°C and maintained the reaction for 3-4 hrs at same temperature. After completion
of the reaction, cooled the reaction mixture to 0-5°C. Reaction mixture pH was adjusted to 2.5-3.5 with
hydrochloric acid at 0-5°C. After that maintained for 1-2 hrs at 0-5°C. Centrifuge the mass & washed with
chilled water and dried at 100-105°C.
Stage-2: Acetonitrile was charged into the reactor and added stage-I material at 25-30°C, then 2,2-
dithiobis(benzothiazole) dissolved in acetonitrile was added into the reaction mass at 25-30°C and stirred for 2-
3 hrs. Then distilled off a portion of acetonitrile under vacuum at 45-50°C and the reaction mixture was cooled
to 25-30°C under nitrogen atmosphere. Cool the reaction mixture to 10-15°C and added acetonitrile and
triethylamine to the reaction mixture at 10-15°C for 30-60 min. Then the reaction mixture was cooled to 0-5°C
and triphenylphosphine was added to the reaction mixture at the same temperature and maintained the
reaction mixture for 1-2 hrs at 0-2°C. After completion of the reaction the reaction mixture was cooled to -10°C
and the reaction was maintained for 4-5 hrs at -10°C to -5°C. Centrifuged the reaction mixture and washed with
chilled methanol. Methanol was taken in the reactor and added above wet material at -10°C to -5°C under
nitrogen atmosphere and the reaction mixture was maintained for 1-2 hrs at -5 to 0°C. Centrifuged the mass
and washed with chilled methanol. Dried the compound to remove solvent.
Stage-3: Tetrahydrofuran was taken into the reactor, water was charged and cooled to 0-5°C. 7-amino-3-vinyl-
3-cephem-4-carboxylic acid and stage-2 materials are added at 0-5°C. The mixture of tetrahydrofuran and
triethylamine was added slowly for 2-3 hrs at 0-5°C. Reaction mixture was maintained 4-5 hrs at 0-5°C. After
completion of the reaction ethyl acetate was added at 0-5°C. Then the reaction mixture was filtered through
hyflow and the bed was washed with ethyl acetate. Separated the layers and aqueous layer is washed with
ethyl acetate at 10-15°C. Then combined ethyl acetate organic layer was washed with water. Carbon was
charged to the aqueous layer at 25°C and stirred for 30-45min. Filtered the reaction mixture through hyflow and
washed the bed with water and the filtrate was cooled to 0-5°C. Sodium hydroxide solution was added to the
filtrate at 0-10°C and maintained for 15-30 min. The reaction mass pH was adjusted to 4.8-5.2 with hydrochloric
acid at 15-20°C. Carbon was charged to the aqueous layer at 25°C and stirred for 30-45 min. Filtered the
reaction mass through hyflow and washed the bed with water. Adjust the pH to 2.0-2.5 by using hydrochloric
acid. Cooled to 30°C and stirred for 3-4hrs at 30-35°C and at 0-5°C for 1-2hrs. Centrifuge the material and
washed with chilled water. Dried the wet compound to get Cefixime.
123
ANNEXURE - IX
PRODUCT : Cefixime
Flow Chart
(Z)-4-Chloro-2-[[(2-methoxy
carbonyl)methoxy]imino]-
acetoacetate
Sodium Acetate Stage I Sol.Recovery
Thiourea Effluent
Water
Stage-1
2,2-Dithio bis (benzothiazole)
Triphenylphosphine Sol.Recovery
Stage II
Acetonitrile Organic Residue
Methanol
Stage-2
7-Amino-8-oxo-3-vinyl-5-thia-1-
azabicyclo[4.2.0]oct-2-ene-2-
carboxylic acid
Stage III
Ethylene Diamine Tetraacetic Oinorganic Solid Waste
acid Spent Carbon
Carbon
Hyflo
Water
Cefixime
124
ANNEXURE - IX
PRODUCT : Cefmetazole
Description :
Stage-1 : 7-[2-[(cyanomethyl)thio]acetamido]-7-methoxycephalosporanic acid is dissolved in acetone and the

solution is cooled to 0 to-5°C. Simultaneously a solution of 2-[(cyanomethyl)thio]acetylchloride in acetone is
added drop wise. Stirred the reaction mixture for 30 min at 5°C. After completion of the reaction, evaporate the
solvent and dissolved the reaction mixture in ethyl acetate. Added anisole, trifluoroacetic acid at 0-5°C and
maintained the reaction for 30 min. After completion of the reaction, filter the reaction mixture The acid solvent
is evaporated and dissolved in water. Reaction mixture pH adjust to 7.5 and the precipitated solid was filtered
and dried to get stage-1.
Stage-2 : 1-Methyl-1H-tetrazole-5-thiol and a solution of sodium hydroxide are taken in a reactor. Stage-1
dissolved in dimethylformamide was added slowly to the above mixture. Heat the reaction mixture and
maintained the reaction mixture for 1-2 hrs. After completion of the reaction. Quench the reaction mixture with
water and filtered the solid. Solid obtained is treated with ether to get pure form of Cefmetazole.
Flow Chart
7-Amino-7-methoxycepholo
sporanic acid benzhydryl ester
2-[(Cyanomethyl)thio] Sol.Recovery
acetylchloride Evaporation Loss
Anisole Stage I Effluent
Trifluoro acetic acid
Water
Stage-1
Dimethylformamide Evaporation Loss
Stage II
1-Methyl-1H-tetrazole-5-thiol Effluent
Diisopropyl ether Organic Residue
Water
Cefmetazole
125
ANNEXURE - IX
PRODUCT : Iloprost
Description :
Stage-1: Methanol and [1[(E)-4methyl-3-oxo-octo-1-en-6-nyl]spiro [1,3-dioxalane-2,5'-2,3,3a,4,6,6a-hexahydro-

1H-pentalene]-2'-yl] benzoate were taken into a reactor. Sodium borohydride is added lot wise at -20°C to a
solution to the above mixture under nitrogen atmosphere. The reaction mixture was stirred at -20°C for one
hour under nitrogen atmosphere. After completion of the reaction, . the reaction mixture was quenched with
25% aqu. hydrochloric acid. And then diluted with dichloromethane and washed with water. Distilled off
dichloromethane layer under vacuum at below 45°C to get oily compound. This crude compound is dissolved in
methanol and added with potassium carbonate. The reaction mixture is stirred at room temperature for 16
hours under nitrogen atmosphere. The reaction mass is filtered and distilled to remove methanol. Diluted the
reaction mixture with dichloromethane and washed dichloromethane layer with water. Distill the
dichloromethane layer to get oily compound. The crude compound is dissolved in Tetrahydropyranyl methyl
ether and paratoluenesulfonic acid is added to the reaction mixture at 0 – 5°C. The reaction mixture is stirred
at 0 – 5°C for 30 – 60min,. After completion of the reaction. Diluted the reaction mixture with water and
extracted with dichloromethane. Washed dichloromethane layer with water and distilled off solvent to get the
desired product as an oil.
Stage-2 : To a solution of triphenyl phosphine acid derivative in dimethylsulfoxide at 10 – 15°C was added
stage-1 for 30– 45 min. The reaction mixture is heated to 40 – 45°C and maintained the reaction mixture at the
same temperature for 2–3 hours. After completion of the reaction, reaction mixture is poured into water.
Acidified the reaction mixture to 4–5 using acetic acid and is extracted with dichloromethane and washed
dichloromethane with water. Distilled dichloromethane layer under vacuum at below 50°C. Added cyclohexane
to the crude compound and heated to 50–55°C to get clear solution. Cooled the reaction mixture to room
temperature. Maintained at room temperature for 3– 4 hours for product separation. Centrifuged the separated
product to get technical grade of Iloprost.
126
ANNEXURE - IX
PRODUCT : Iloprost
Flow Chart
[1'[(E)-4-Methyl-3-oxo-octo-1-
en-6-ynyl]spiro[1,3-dioxalane-
2,5'-2,3,3a,4,6,6a-hexahydro-
1H-pentalene]-2'-yl]benzoate
Tetrahydropyranyl methyl ether
Sol.Recovery
p-Toluene Sulfonic acid Evaporation Loss
Stage I
Sodium Borohydride Organic Residue
Methanol
Water
Stage-1
5-(Triphenylphosphoranyl
idene) pentanoic acid Sol.Recovery
Stage II
Dimethyl Sulfoxide Organic Residue
Cyclohexane
Water
Iloprost
127
ANNEXURE - IX
PRODUCT : Aripiprazole
Description :
Stage-1 : 7-Hydroxy carbostyril is reacts with 1,4-Dibromobutane in the presence of Potassium Carbonate in
Acetone and Cyclohexane media to get Stage-1 (Crude).
Stage-2 : Stage-1 (Crude) is purified in Toluene solvent media to get Stage-2 (Pure).
Stage-3 : Stage-2 (Pure) is reacts with 2,3-Dichlorophenyl Piperazine Hydrochloride in the presence of
Triethylamine in Methanol solvent media to get Aripiprazole (Crude).
Stage-4 : Aripiprazole (Crude) is purified in the presence of Carbon in Isopropyl Alcohol solvent media to get
Aripiprazole (Pure).
Flow Chart
7-Hydroxy carbostyril
1,4-Dibromobutane
Potassium Carbonate
Acetone Sol.Recovery
Stage I
Cyclohexane Inorganic Solid Waste
Hyflo
Water
Stage-1 (Crude) Sol.Recovery

Toluene Stage II Evaporation Loss
Organic Residue
Stage-2 (Pure)
2,3-Dichlorophenyl Piperazine Sol.Recovery
Hydrochloride Evaporation Loss
Stage III
Water
Aripiprazole (Crude) Sol.Recovery

Carbon Stage IV Organic Residue
Hyflo Inorganic Solid Waste
Spent Carbon
Aripiprazole
128
ANNEXURE - IX
PRODUCT : Brivaracetam
Description :
Stage-1 : Toluene charged into the reactor. S-2-Aminobutyramide charged into the reactor. Cooled the
reaction mass to 20-25°C. 4-n-Propylhydroxyfuranone was charged into the reactor and stirred for 30-45 min at
20-25°C. Sodium borohydride and water added into the reactor and maintained for 1 hr. Then acetic acid was
added and heated the reaction mass to 50-55°C and maintained for 3-4 hrs. Then reacton mass cooled to 20-
30°C and maintained for 10-12 hrs. Reaction completed was checked by TLC.Water added to the reaction
mass and layer separated. Toluene distilled and cooled the mass to 20-25°C. Toluene charged into the reactor
for crystalization and maintained for 1 hr to 1 hr 30 min and centrifuged the material as Stage-1.
Stage-2 : Water, stage-1 and ammonium formate were charged into the reactor under argon gas. Reaction
mass heated to 50-55oC and maintained for 3 hrs. Then cooled the reaction mass to 20-30°C and maintained
for 15-17 hrs. Reaction completion was checked by TLC. EthylAcetate was charged into the reaction mass.
Layers separated and ethyl acetate layer was washed with water. Ethyl Acetate distilled completely and cooled
the reaction mass to 20-30°C. Then diisopropyl ether was charged into the reactor. Stirred for 1 hr centrifuged
the material to get the Brivaracetam.
129
ANNEXURE - IX
Flow Chart
4-N-Propylhydroxy furanone
5-2-Aminobutyramide Sol.Recovery
Stage I
Water
Ammoniumformate Evaporation Loss
Ethyl Acetate Stage II Effluent
Diisopropyl Ether Organic Residue
Brivaracetam
130
ANNEXURE - IX
PRODUCT : Asenapine Maleate
Description :
Stage-1 : Charged 2-chlorophenyl acetic acid and Methylene dichloride into reactor at 25-30oC. Cooled the
reaction mass to 5-10oC under nitrogen atmosphere. Charged dicyclocarbodiimide followed by triethyl amine
into the reaction mass.Added sarcosine methyl ester at 5-10oC . Maintained the reaction mass for 2-3 hours.
After completion of the reaction, filtered dicyclo hexyl urea and washed the bed with Methylene dichloride.
Combined the total organic layer and washed with water. Organic layer distilled under vacuum at 40-50oC and
yellow coloured liquid obtained as stage-1.
Stage-2 : Charged stage-1 compound and toluene into the reactor at 25-30oC under nitrogen atmosphere.
Potassium tertiary butoxide was added at 25-30oC. Maintained the reaction mass at 25-30oC for 3-4 hours.
After completion of the reaction, water was added into the reaction mass and stirred for 30-45 minutes.
Separated the organic layer and aqueous layers. Conc.HCl was added to the aqueous layer slowly dropwise at
5-10oC. The precipitated product was filtered by nutch filter and washed with water. Product was dried at 45-
50oC.
Stage-3 : Charged stage-2 compound and 1,4-dioxane, potassium carbonate into reactor. Added 4-chloro
phenol into the rector. Heated the reaction mass to reflux and maintained under reflux for 24 hours. Cooled the
reaction mixture to 25-30oC after completion of the reaction. Filtered the inorganics using nutch filter.
Concentrated the organic layer for recovery solvent dioxane and water was added to the obtained residue.
Concentrated HCl was added to the reaction mass upto pH 2. Product was filtered and washed with water.
Dried the product at 50-60oC.
Stage-4 : Charged Phosphorous pentoxide and phosphoric acid into reactor under nitrogen atmosphere.
Charge stage-3 compound into the reactor. Heat the reaction mass to 120oC and maintain for 48 hours. Cool
the reaction mixture to 25-30oC and chilled water was flown into the reaction mass. Stirred the reaction mass at
25-30oC for 3-4 hours. Product was extracted in water and organic layer washed with brine solution.
Concentrated the organic layer and methanol was added into the reaction mixture. Cool the suspension to 0-
5oC and filtered the product and dried at 45-50oC.
Stage-5 : Charged stage-4 compound and methanol into the reactor at 25-30oC .Magnesium turnings were
added in lots at 25-30oC and the reaction mass maintained at 45-50oC for 6 hours. After completion of the
reaction water was added into the reaction mixture followed by quenched with dilute hydrochloric acid. Product
was extracted in ethyl acetate and washed the organic layer with brine solution. Concentrated the organic layer
to minimum volume and cooled to 0-5oC. Filtered the product and dried at 50-55oC.
Stage-6 : Charged Aluminium chloride and THF into the reactor under nitrogen atmosphere. Cooled the
reaction mixture to -20oC. Lithium aluminium hydride was added carefully by taking all the precautions under
nitrogen atmosphere below -20oC and maintained the complex for 30 minutes. Stage-4 dissolved in THF was
added to the prepared complex and maintained for 1 hour. Quenched the reaction mass carefully using sodium
hydroxide solution. Product was extracted into ethyl acetate and washed with brine solution. Concentrated the
organic layer under vacuum at 45-50oC. The obtained residue dissolved in 2-propanol and maelicacid was
charged into the reaction mass. Maintained the reaction mass for 2-3 hours. The precipitated product was
centrifuged and washed with 2-propanol. Upon drying at 50-60oC under vacuum for 5-6 hours affords
Asenapine Maleate in pure form.
131
ANNEXURE - IX
Flow Chart
2-Chloro phenylacetic acid
Savcosine methyl ester
Hydrochloride Sol.Recovery
Dicyclohexylcarbodiimide Stage I Evaporation Loss
Water
Stage-1
Potassium tert-Butaoxide Sol.Recovery
Toluene Stage II Evaporation Loss
4-Chlorophenol Evaporation Loss
Stage III
1,4-Dioxane Organic Residue
Hydrochloric acid (35%) Process Emissions
Water
Phosphoric acid Evaporation Loss
Phosphorous Pentaoxide Stage IV Effluent
Ethyl Acetate
Stage-4
Magnesium Turnings Sol.Recovery
Stage V
132
ANNEXURE - IX
Flow Chart
Stage-5
Aluminium Chloride
Lithium Aluminium Hydride Sol.Recovery
Maleic acid Evaporation Loss
Sodium Hydroxide Stage VI Effluent
Tetrahydrofuran
Water
Asenapine Maleate
133
ANNEXURE - IX
PRODUCT : Ramipril
Description :
Stage-1 : L-Serine methylester.HCl reacts with Acetic Anhydride in presence of Potassium Carbonate,
Hydrochloric acid and Toluene gives Methyl-β-chloro-α-acetamido propionate.
Stage-2 : Methyl-β-chloro-α-acetamido propionate reacts with Cyclopentanone in presence of Potassium

Carbonate and Toluene gives 1-Acetylamino-2-(2-oxocyclopentyl) propionic acid methyl ester.
Stage-3 : 1-Acetylamino-2-(2-oxocyclopentyl) propionic acid methyl ester cyclises in presence of Hydrochloric

acid and water give 2-Azabicyclo-(3,3,0)-octene-3-Carboxylic acid.
Stage-4 : 2-Azabicyclo-(3,3,0)-octene-3-Carboxylic acid on hydrogenation with Hydrogen on Palladium carbon

in presence of Methanol gives 2-Azabicyclo-(3,3,0)-octane-3-Carboxylic acid.
Stage-5 : 2-Azabicyclo-(3,3,0)-octane-3-Carboxylic acid reacts with Benzylalcohol in presence of Sulfuric acid

and Toluene gives 2-Azabicyclo-(3,3,0)-octane-3-Carboxylic acid benzyl ester.
Stage-6 : 2-Azabicyclo-(3,3,0)-octane-3-Carboxylic acid benzyl ester reacts with ECPP Alanine in presence of
Toluene and Acetone gives Ramipril Benzyl ester.
Stage-7 : Ramipril Benzyl ester on hydrogenation with Hydrogen on Palladium Carbon in presence of Methanol
gives Ramipril.
134
ANNEXURE - IX
PRODUCT : Ramipril
Flow Chart
L-Serine methylester
Hydrochloride Sol.Recovery
Acetic Anhydride Evaporation Loss
Toluene Stage I Effluent
Potassium Carbonate Organic Residue
Hydrochloric Acid (35%) Process Emissions
Water
Stage-1
Cyclopentanone Sol.Recovery
Toluene Evaporation Loss
Stage II
Process Emissions
Hydrochloric Acid (35%) Evaporation Loss
Stage III
Xylene Effluent
Methanol Effluent
Stage IV
Hyflo Organic Residue
Hydrogen Inorganic Solid Waste
Stage-4
Benzylalcohol Sol.Recovery
Sulfuric Acid Stage V Evaporation Loss
Toluene Effluent
Water
Stage-5
ECPP Alanine Sol.Recovery
Para Toluene sulfonic acid Evaporation Loss
Stage VI
Toluene Effluent
Water
Methanol Effluent
Hyflo Stage VII Organic Residue
Hydrogen Inorganic Solid Waste
Ramipril
135
ANNEXURE - IX
PRODUCT : Zileuton
Description :
Stage-1: Charge methanol to 2-Acetyl benzo[b] thiophene taken in the reactor. Slowly charge sodium
borohydride (take all safety precautions before charging sodium borohydride, nitrogen blanket is maintained
through out) to the above mixture and maintained for 1-2 hours. After completion of the reaction, quenched the
reaction mixture with water and distilled off methanol completely. Charged water to the reaction mass and
adjusted reaction mass pH 7-8, further cooled to 10-15°C, filtered and dried to obtain Stage-1 product.
Stage-2 : Toluene, N-Hydroxyphenylcarbonate and stage-1 compound was charged in to a reactor, Then
slowly added aqueous hydrochloric acid to the reaction mixture. Heated to reaction mixture to the reflux and
maintain at reflux till the completion of the reaction. Cooled the reaction mixture to 25-30°C and solid
precipitated is filtered off and dried to obtain stage-2 product.
Stage-3 : Methanol was charged in to a reactor and cooled to 5-10°C and then added liquid ammonia. Charge
stage-2 product and stirred the reaction mixture at 25-30°C for 50-60 hrs. After completion of the reaction,
distilled off methanol from the reaction mixture and extracted the reaction mixture with toluene and wash with
water. Distilled off toluene to get the product.
Stage-4 : Take ethyl acetate in to a reactor and charge stage-3 product. Heat to reflux and charge carbon and
filtere the mass through hyflow bed. Cooled the reaction mass to 0-5°C and fileterd off to obtain Zileuton.
Flow Chart
2-Acetylbenzo[b]thiophene Sol.Recovery
Hydrochloric acid (35%) Stage I Effluent
Stage-1
N-Hydroxy phenyl carbonate Sol.Recovery
Hydrochloric acid (35%) Stage II Evaporation Loss
Toluene Effluent
Stage-2
Liq.Ammonia (20%) Sol.Recovery
Methanol Stage III Evaporation Loss
Toluene Effluent
Stage IV
Spent Carbon
Zileuton
136
ANNEXURE - IX
PRODUCT : Vildagliptin
Description :
Stage-1: Amantadine hydrochloride dissolved in dichloromethane is taken in a reactor. To this added nitration
mixture [nitric acid + sulfuric acid]. Followed by hydroxylated in presence of a sodium hydroxide. The reaction
mixture extracted with dichloromethane and washed with water. Concentrated the dichloromethane and isolated
the solid in cyclohexane.
Stage-2: Compound obtained in Stage-1 reacts with (S)-1-(2-chloroacetyl)pyrrolidine-2-carbonitrile in the
presence of tetrahydrofuran, potassium carbonate and potassium iodide at reflux temperature. After the
completion of reaction, distilled off solvent and dissolved the crude in ethyl acetate. Cool the reaction mixture to
0-5 ° C filter the precipitated solid to get Vildagliptin.
Flow Chart
Amantadine Hydrochloride
Nitric acid (70%)
Sulfuric acid Sol.Recovery
Sodium Hydroxide Stage I Evaporation Loss
Cyclohexane Organic Residue
Water
Stage-1
(3)-1-(2-Chloroacytyl)pyrrolide- Sol.Recovery
2-carbonitrile Evaporation Loss
Potassium Carbonate Stage II Organic Residue
Potassium Iodide Inorganic Solid Waste
Ethyl Acetate
Vildagliptin
137
ANNEXURE - IX
PRODUCT : Palonosetron Hydrochloride
Description :
Stage 1: (S)-N-(1-Azabicyclo[2,2,2]oct-3-yl)-5,6,7,8-Tetrahydro-1-naphthalene carboxamide on reaction with

Hydrochloric Acid in presence of Diemthyl formamide in Tetrahydrofuran solvent medium to form Stage-1
compound.
Stage 2: Stage-1 on reaction with Hydrogen Chloride in presence of Sodium Hydroxide and Palladium Carbon
catalyst in Toluene and IMS as solvent media to get Palonosetron Hydrochloride.
Flow Chart
(S)-N-(1-Azabicyclo[2,2,2]oct-3-
yl)-5,6,7,8-tetrahydro-1- Sol.Recovery
naphthalene carboxamide Evaporation Loss
Tetrahydrofuran Stage I Effluent
Diemthylformamide Organic Residue
Hydrochloric Acid (35%)
Water
Stage-1
Sodium Hydroxide
Toluene Sol.Recovery
Stage II
Ethanol Effluent
Hydrogen Chloride Process Emissions
Water
Palonosetron Hydrochloride
138
ANNEXURE - IX
PRODUCT : Salmeterol Xinafoate
Description :
Stage-1: 4-Phenyl butoxy chlorohexane reacts with 4-Hydroxy-alpha'-aminomethyl metaxylene-alpha, alpha'-diol
in presence of Triethylamine in Toluene and Methanol as solvent media to get Salmeterol Base.
Stage-2: Salmeterol Base on reaction with 1-Hydroxy-2-naphthoic acid in presence of Acetone solvent medium to
form Salmeterol Xinafoate.
Flow Chart
4-Phenylbutoxy chlorohexane
4-Hydroxy-α'-aminomethyl
metaxylene-α,α'-diol Sol.Recovery
Triethylamine Stage I Evaporation Loss
Toluene Effluent
Water
Salmeterol Base
1-Hydroxy-2-naphthoic acid Sol.Recovery
Stage II
Organic Residue
Salmeterol Xinafoate
139
ANNEXURE - IX
PRODUCT : Trandolapril
Description :
Stage-1 : 1H-Indole-2-carboxylic acid is reacts with Rhodium on Carbon under Hydrogen gas with a pressure in
Methanol solvent media to get Stage-1 intermediate.
Stage-2 : Stage-1 intermediate is reacts with Benzyl Alcohol and 1,3-Dicyclohexyl carbodiimide in Toluene
Stage-3 : Stage-2 intermediate is reacts with Mandelic Acid in the presence of Potassium Carbonate in Acetone
and Toluene solvent media to get Stage-3 intermediate.
Stage-4 : Benzene is reacts with Maleic Anhydride in the presence of Aluminum Chloride and Hydrochloric acid
in Acetone solvent media to get Stage-4 intermediate.
Stage-5 : Stage-4 intermediate is reacts with Sulfuric Acid and Ethanol in the presence of Sodium Carbonate in
Methylene Dichloride solvent media to get Stage-5 intermediate.
Stage-6 : Alanine is reacts with P-Toluene Sulfonic Acid and Benzyl Alcohol in Toluene and Methanol solvent
media to get Stage-6 intermediate.
Stage-7 : Stage-5 intermediate is reacts with Stage-6 intermediate in Toluene and Acetone solvent media to get
Stage-7 intermediate.
Stage-8 : Applying the Hydrogen gas with pressure to Stage-7 intermediate in the presence of Palladium
Carbon Toluene and Methanol solvent media to get Stage-8 intermediate.
Stage-9 : Stage-8 intermediate is reacts with Stage-3 intermediate and 1,3-Dicyclohexyl carbodiimide in
Toluene and Methanol solvent media to get Stage-9 intermediate .
Stage-10 : Applying the Hydrogen gas with pressure to Stage-9 intermediate in the presence of Palladium
Carbon Toluene and Methanol solvent media to get Trandolapril.
140
ANNEXURE - IX
Flow Chart
1H-Indole-2-carboxylic acid Sol.Recovery
Rhodium on Carbon Stage I Organic Residue
Stage-1
1,3-Dicyclohexylcarbodiimide Stage II Evaporation Loss
Toluene Effluent
Stage-2
Mandelic Acid Sol.Recovery
Stage III
Benzene
Maleic Anhydride Sol.Recovery
Aluminum Chloride Evaporation Loss
Stage IV
Acetone Effluent
Hydrochloric Acid (35%) Organic Residue
Stage-4
Sulfuric Acid Sol.Recovery
Ethanol Evaporation Loss
Stage V
Sodium Carbonate Process Emissions
Water
Alanine
p-Toluenesulfonic acid Evaporation Loss
Stage VI
Toluene Effluent
Water
141
ANNEXURE - IX
Flow Chart
Stage-5
Toluene Stage VII Evaporation Loss
Acetone Effluent
Stage-7
StageVIII
Toluene Effluent
Stage-3
1,3-Dicyclohexyl carbodiimide Evaporation Loss
Stage IX
Toluene Effluent
Water
Stage-9
Toluene Effluent
Stage X
Carbon Inorganic Solid Waste
Hyflo Spent Carbon
Trandolapril
142
ANNEXURE - IX
PRODUCT : Ecabapide
Description :
Stage-1 : 2-Chloro-N-(2-(3,4-dimethoxyphenyl)ethyl)acetamide condensation with 3-amino-N-methyl

benzamide in the presence of calcium carbonate and sodium iodide in dimethylformamide medium .After
completion of the reaction distill off DMF. Extract the reaction mass with chloroform.wash the chloroform layer
with water.Distill off chloroform layer,then isolate the solid in Ethanol and methanol to give stage-1 product.
Stage-2 : Stage-1 free base with sodiumcarbonate solution in Dichloromethane.After distillation of DCM
isolated solid in Methanol to give 3-((2-((2-(3,4-dimethoxyphenyl)ethyl)-amino)-2-oxoethyl)amino)-N-
methylbenzamide (Ecabapide).
Flow Chart
2-Chloro-N-(2-(3,4-dimethoxy
phenyl)ethyl) acetamide
3-Amino-N-methyl benzamide
Calcium Carbonate
Sodium Iodide Sol.Recovery
Chloroform Stage I Effluent
Sodium Bisulfite (5%) Organic Residue
Sodium Chloride (10%) Process Emissions
Methanol
Ethanol
Diethyl Ether
Stage-1
Methylene Dichloride Sol.Recovery
Sodium Carbonate (10%) Evaporation Loss
Stage II
Methanol Effluent
Diethyl Ether Organic Residue
Ecabapide
143
ANNEXURE - IX
PRODUCT : Zafirlukast
Description :
Stage-1 : 5-Nitro-1H-indole is reacts with Methyl-4-(bromomethyl)-3-methoxy bezoate in the presence of
Sodium Carbonate in Toluene and Acetone solvent media to get Stage-1 intermediate.
Stage-2 : Stage-1 intermediate is reacts with Dimethylsulfate in the presence of Sodium Hydroxide to get Stage-
2 intermediate.
Stage-3 : Stage-2 intermediate forms Stage-3 intermediate under Hydrogen gas pressure in the presence of
Palladium Carbon.
Stage-4 : Stage-3 intermediate is reacts with Cyclopentyl chloroformate in the presence of Sodium Carbonate
in Toluene and Acetone solvent media to get Stage-4 intermediate.
Stage-5 : Stage-4 intermediate is reacts with Ortho Toluene Sulfonamide in Methanol solvent media to get
Zafirlukast.
Flow Chart
5-Nitro-1H-indole
Methyl-4-(bromomethyl)-3- Sol.Recovery
methoxy bezoate Evaporation Loss
Acetone Stage I Effluent
Water
Stage-1
Dimethylsulfate
Stage II
Water
Stage-2 Recovery
Hydrogen Effluent
Palladium Carbon Stage III Inorganic Solid Waste
Water
Stage-3
Cyclopentyl chloroformate Sol.Recovery
Sodium Carbonate Evaporation Loss
Stage IV
Toluene Effluent
Ortho Toluene Sulfonamide Stage V Evaporation Loss
Zafirlukast
144
ANNEXURE - IX
PRODUCT : Darifenacin Hydrobromide
Description :
Stage-1 : 3(S)-(1-Carbamoyl-1,1-diphenyl methyl) pyrrolidine is reacts with 5-(2-Bromoethyl)-2,3-dihydro

benzofuran in the presence of Sodium Methoxide in Methylene Dichloride solvent media to get Darifenacin.
Stage-2 : Darifenacin is reacts with Hydrogen Bromide in Acetone solvent media to get Darifenacin
Hydrobromide.
Flow Chart
3(S)-(1-Carbamoyl-1,1-
diphenyl methyl) pyrrolidine
5-(2-Bromoethyl)-2,3-dihydro Sol.Recovery
benzofuran Stage I Evaporation Loss
Sodium Methoxide Effluent
Water
Darifenacin Sol.Recovery
Hydrogen Bromide Stage II Evaporation Loss
Darifenacin Hydrobromide
145
ANNEXURE - IX
PRODUCT : Dapoxetine Hydrochloride
Description :
Stage-1 : Benzene reacts with 3-Chloropropanoyl Chloride in presence of Aluminium Chloride and Hydrochloric
acid using Methylene Dichloride as a solvent medium to give 3-Chloro-1-phenylpropan-1-one.
Stage-2 : 3-Chloro-1-phenylpropan-1-one reacts with Sodium Borohydride in presence of Methanol and Acetic acid
in Methylene Dichloride solvent medium to get 3-Chloro-1-phenylpropan-1-ol.
Stage-3 : 3-Chloro-1-phenylpropan-1-ol condensed with 1-Napthol in presence of Potassium Carbonate, Sodium

Hydroxide and Sodium Sulfate in Dimethylformamide solvent medium to form 3-(Naphthalen-1-yloxy)-1-phenyl
propan-1-ol.
Stage-4 : 3-(Naphthalen-1-yloxy)-1-phenylpropan-1-ol reacts with Methanesulphonyl Chloride in presence of
Triethylamine and further reacts with Dimethylamine in presence of Dimethylaminopyridine, Hydrochloric acid and
Sodium Hydroxide in Toluene solvent medium to give N,N-Dimethyl-3-(naphthalen-1-yloxy)-1-phenylpropan-1-
amine.
Stage-5 : Resolution of N,N-Dimethyl-3-(naphthalen-1-yloxy)-1-phenylpropan-1-amine in presence of D-(-) Tartaric
acid in Ehyl Acetate as a solvent medium to get N,N-Dimethyl-3-(naphthalen-1-yloxy)-1-phenylpropan-1-amine
tartarate salt.
Stage-6 : N,N-Dimethyl-3-(naphthalen-1-yloxy)-1-phenylpropan-1-amine tartarate salt treated with Sodium
Hydroxide and followed by salt formation with Hydrogen Chloride in presence of Sodium Sulfate in Isopropyl
Alcohol and Methylene Dichloride as solvent media to form Dapoxetine Hydrochloride.
146
ANNEXURE - IX
Flow Chart
Benzene Sol.Recovery
3-Chloropropanoyl Chloride Evaporation Loss
Aluminium Chloride Effluent
Methylene Dichloride Stage I Organic Residue
R-505
Methanol Stage II Organic Residue
Acetic acid
Water
R-505 Process Emissions
Naphthol Effluent
Potassium Carbonate
Stage III
Sodium Hydroxide
Sodium Sulfate
Toluene
Stage-3 in Toluene (162+1085) Sol.Recovery

Methanesulfonyl Chloride Evaporation Loss
Dimethylamine (40%) Organic Residue
Dimethylaminopyridine Stage IV
Sodium Hydroxide
Ethyl Acetate
Water
Stage-4 in Ethyl Acetate Sol.Recovery

(162+830) Evaporation Loss
D-(-)Tartaric acid Stage V Effluent
Water
Sodium Sulfate Stage VI
Hydrogen Chloride Spent Carbon
Carbon
Dapoxetine Hydrochloride
147
ANNEXURE - IX
PRODUCT : Ibudilast
Description :
Stage-1 : Hydroxylamine Hydrochloride reacts with Chlorosulfonic acid in presence of Methylene Dichloride solvent
medium to give Hydroxyl amine-O-sulfonic acid (Stage 1).
Stage-2 : Hydroxyl amine-O-sulfonic acid further reaction with 2-Methylpyridine followed by salt formation with
Hydrobromic acid in presence of Isopropyl Alcohol and Ethyl Acetate solvent media to get 1-Amino-2-
methylpyridinium bromide (Stage 2).
Stage-3 : 1-Amino-2-methylpyridinium bromide further reaction with Isobutyric Anhydride in presence of Isopropyl
Alcohol solvent medium to form 1-Isobutyramido-2-methylpyridinium bromide (Stage 3).
Stage-4 : 1-Isobutyramido-2-methylpyridinium bromide further reaction with Isobutyric Anhydride in presence of

Potassium Carbonate and Sodium Hydroxide in Methylene Dichloride and n-Hexane solvent media to obtain
Ibudilast.
148
ANNEXURE - IX
PRODUCT : Ibudilast
Flow Chart
Hydroxylamine Hydrochloride Sol.Recovery
Chlorosulfonic acid Evaporation Loss
Stage I
Process Emissions
Stage-1
2-Methylpyridine
Hydrobromic acid (48%) Stage II Evaporation Loss
Isopropyl Alcohol Effluent
Water
Isobutyric Anhydride Stage III Evaporation Loss
Stage-3
Potassium Carbonate Sol.Recovery
Isobutyric Anhydride Evaporation Loss
Stage IV
Sodium Hydroxide Organic Residue
n-Hexane Spent Carbon
Carbon Process Emissions
Water
Ibudilast
149
ANNEXURE - IX
PRODUCT : Mesalamine
Description :
Stage-1 : 2-Hydroxy-5-Nitrobenzoic acid on reduction in presence of Raney Nickel, Sodium Hydroxide and
Hydrogen Chloride in aqueous medium to obtain Mesalamine.
Flow Chart
2-Hydroxy-5-Nitrobenzoic acid
Raney Nickel
Hydrogen Recovery
Stage I
Hydrose Spent Carbon
Carbon Process Emissions
Hydrogen Chloride
Water
Mesalamine
150
ANNEXURE - IX
PRODUCT : Pregabalin
Description :
Stage-1 : D,L-Pregabalin is reacts with Mandelic Acid in Methanol solvent medium to get S-Pregabalin
Mandalate.
Stage-2 : S-Pregabalin Mandalate is reacts with Sodium Bicarbonate in Methylene Dichloride solvent medium
to give Pregabalin (Crude).
Stage-3 : Pregabalin (Crude) is on purification with Methanol solvent medium to get Pregabalin (Pure).
Flow Chart
D,L-Pregabalin Sol.Recovery
Mandelic Acid Stage I Evaporation Loss
S-Pregabalin Mandalate Sol.Recovery

Sodium Bicarbonate Stage II Effluent
Process Emissions
Pregabalin (Crude) Sol.Recovery

Methanol Stage III Evaporation Loss
Organic Residue
Pregabalin
151
ANNEXURE - IX
PRODUCT : Sumatriptan Succinate
Description :
Stage-1 : (4-Hydrazinyl phenyl) metane sulfonyl chloride reacts with Methylamine in presence of Triethylamine
in Methylene Dichloride and Acetone solvent media to get Stage-1 Intermediate.
Stage-2 : Stage-1 Intermediate is reacts with 4-Chloro-1-hydroxy butane sulfonic acid sodium salt in the
presence of Sodium Methoxide in Toluene and Methanol solvent media to form Stage-2 Compound.
Stage-3 : Stage-2 Compound is reacted with Dimethylamine in presence of Toluene solvent medium to get
Sumatriptan.
Stage-4 : Sumatriptan is reacts with Succinic acid in presence of Methanol solvent medium to obtain
Sumatriptan Succinate.
Flow Chart
(4-Hydrazinyl phenyl) metane
sulfonyl chloride
Methylamine (40%) Sol.Recovery
Triethylamine Stage I Evaporation Loss
Water
Stage-1
4-Chloro-1-hydroxy butane
sulfonic acid sodium salt Sol.Recovery
Sodium Methoxide Stage II Evaporation Loss
Toluene Effluent
Water
Dimethylamine Evaporation Loss
Stage III
Toluene Effluent
Sumatriptan Sol.Recovery
Succinic acid Stage IV Evaporation Loss
Venlafaxine Hydrochloride
152
ANNEXURE - IX
PRODUCT : Voriconazole
Description :
Stage-1 : 3-(6-Chloro-5-fluoropyrimidin-4-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl) butan-2-ol on
reduction with Hydrogen in presence of Sodium Acetate and Raney Nickel as catalyst in Methanol solvent
medium to form Stage-1 Compound.
Stage-2 : Stage-1 Compound on rection with R(-)-10-Camphorsulfonic Acid in presence of Acetone and Methanol
solvent media to get Stage-2 Intermediate.
Stage-3 : Stage-2 Intermediate reacts with Sodium Hydroxide in presence of Methylene Dichloride and Propanol
solvent media to obtain Voriconazole.
Flow Chart
3-(6-Chloro-5-fluoropyrimidin-4-
yl)-2-(2,4-difluorophenyl)-1-(1H-
1,2,4-triazol-1-yl) butan-2-ol Sol.Recovery
Sodium Acetate Evaporation Loss
Stage I
Raney Nickel Effluent
Water
Stage-1
R(-)-10-Camphorsulfonic Acid Sol.Recovery
Stage II
Stage-2
Methylene Dichloride Stage III Evaporation Loss
Propanol Effluent
Voriconazole
153
ANNEXURE - IX
PRODUCT : Gemifloxacin Mesylate
Description :
Stage-1 : Methanol and (Z)-tert-butyl 3-((tert-butoxycarbonylamino)methyl)-4-(methoxyimino)pyrrolidine-1-

carboxylate taken in reactor and cooled to 15-20°C. Under nitrogen atmosphere, slowly added
Methanesulphonoic acid and water at below 30°C. Reaction mass maintained for 16-20 hrs at 20-25°C. Filtered
the compound and washed with Methanol and dried at 60-70°C to get Stage-1 compound.
Stage-2 : Initially, water was charged into the reactor & added Gemiacid material, Cooled to 15-20°C and
Triethylamine was added. Reaction mass maintained at 15-20°C for 20 min then Stage 1 compound added
along with ethanol. Recation mass maintained for 17-18 hrs at 20-25°C. Filtered the compound and washed with
water. Dried the compound at 70-80°C to get Stage-2 compound.
Stage-3 : Isopropyl Alcohol and water was initially taken in reactor and charged Stage compound. Reaction
mass heated to 40-45°C. Slowly added Methanesulphonic acid in the reaction mass at 40-45°C. Check
dissolution. Carbon charged in the reaction mass and maintained at 40-45°C for 15 min. filtered the reaction
mass through hyflow bed and washed with Isopropyl Alcohol. Filtrate cooled to 25-30°C and maintained for 3-4
hrs then cooled to 0-5°C and maintained for 1-2 hrs. filtered the compound and washed with Isopropyl Alcohol.
Dried the compound at 60-70°C to get Gemifloxacin Mesylate.
Flow Chart
(Z)-tert-Butyl-3-{(tert-butoxy
carbonyl amino)methyl)-4- Sol.Recovery
(methoxyimino) pyrrolidine-1- Evaporation Loss
carboxylate Stage I Effluent
Methanesulfonic acid Organic Residue
Methanol Process Emissions
Water
Stage-1
Gemic acid Sol.Recovery
Triethylamine Stage II Evaporation Loss
Ethanol Effluent
Methanesulfonic acid Evaporation Loss
Isopropyl Alcohol Stage III Effluent
Water Spent Carbon
Gemifloxacin Mesylate
154
ANNEXURE - IX
PRODUCT : Rasagiline Mesylate
Description :
Stage-1 : Acetonitrile was used as a solvent. Initially, Indane hydrochloride was charged into reactor then
toluene and potassium carbonate was charged. heat the reaction mass to reflux then add propargyl chloride.
Stir the reaction mixture till the completion of reaction. After completion of reaction distill off Acetonitrile and
cool the reaction mixture charge water and Toluene. Stir for 10 minutes. Separate the layers. Distill off solvent
completely. Unload the material.
Stage-2 : Initially, Acetone was charged into the reactor & added stage-I material and Methane sulphonic acid,
heated up to reflux Stir at reflux for 30 minutes. Cool the reaction mass to 0-5 ° C stir at 0-5 ° C for 2 hours.
Then centrifuged the mass collect the material of Rasagiline Mesylate.
Flow Chart
Indane Hydrochloride
Propargyl Chloride Sol.Recovery
Stage I
Acetonitrile Effluent
Methane Sulfonic aicd Stage II Evaporation Loss
Rasagiline Mesylate
155
ANNEXURE - IX
PRODUCT : Valsartan
Description :
Stage-1 : (S)-Methyl-2-amino-3-methyl butanoate Hydrochloride reacts with 2-Cyano-4'-Bromomethylbiphenyl in
presence of Potassium Carbonate, Hydrochloric acid and Sodium Carbonate in Ethyl Acetate and Toluene solvent
media gives Stage-1 Compound.
Stage-2 : Stage-1 Compound further reacts with Valeryl Chloride in presence of Triethylamine and Sodium
Carbonate in aqueous medium to get Stage-2 Intermediate.
Stage-3 : Stage-2 Intermediate further reacts Sodium azide in presence of Tributyltin Chloride and further
hydrolysis with base Sodium Hydroxide in presence of Hydrochloric acid in Toluene solvent medium to obtain
Valsartan.
Flow Chart
(S)-Methyl-2-amino-3-methyl
butanoate Hydrochloride
2-Cyano-4'-Bromomethylbiphenyl Sol.Recovery
Ethyl Acetate Stage I Effluent
Toluene
Water
Stage-1 in Toluene (60+270)

Triethylamine
Valeryl Chloride Stage II Effluent
Sodium Carbonate
Water
Stage-2 in Toluene (65+270)

Tributyltin Chloride
Sodium Azide Sol.Recovery
Sodium Hydroxide Stage III Evaporation Loss
Water
Valsartan
156
ANNEXURE - IX
PRODUCT : Zonisamide
Description :
Stage-1 : 4-Hydroxy-2-oxo-2H-chromen-3-ylium reacts with Hydroxylamine hydrochloride in presence of

Sodium hydroxide and water to give 2-(Benzo[d]isoxazol-3-yl) acetic acid (Stage-1) compound.
Stage-2 : 2-(Benzo[d]isoxazol-3-yl) acetic acid (Stage-1) reacts with Chlorosulfonic acid in presence of Ethyl
acetate as a solvent media and Sodium hydroxide base, further chlorination with Phosphorous oxychloride in
presence of Toluene as a solvent media, further reaction with ammonia to give Zonisamide (crude).
Stage-3 : Zonisamide (crude) further purification in Ethyl acetate solvent to gives Zonisamide (pure).
157
ANNEXURE - IX
Flow Chart
4-Hydroxy-2-oxo-2H-chromen-3-ylium
Hydroxylamine Hydrochloride
Sodium Hydroxide Stage I Effluent
Water
Stage-1
Ethyl Acetate Sol.Recovery
Chlorosulfonic acid Evaporation Loss
Stage II
Phosphorous Oxychloride Process Emissions
Ammonia gas
Water
Zonisamide (Crude) Sol.Recovery

Ethyl Acelate Evaporation Loss
Carbon Stage III Organic Residue
Hyflow Spent Carbon
Zonisamide
158
ANNEXURE - IX
PRODUCT : Mirtazapine
Description :
Stage-1 : 1-Methyl-3-phenylpiperazine condensation with 2-Chloronicotinonitrile in presence of Potassium
fluoride, further hydrolysis in Potassium hydroxide basic media to give 2-(4-methyl-2-phenylpiperazin-1-
yl)nicotinic acid (Stage-1) compound.
Stage-2 : The 2-(4-methyj-2-phenylpiperazin-1-yl)nicotinic acid (Stage-1) under goes reduction with Vitride in
Toluene solvent media to gives (2•(4-methyl-2-phenylpiperazin-1-yl)pyridin-3-yl)methanol (Stage-2) compound.
Stage-3 : The (2•(4•Methy1-2-pheny1piperazin-1-yl)pyrldin-3-yl)methanol (Stage-2) further reaction with

Sulfuric acid and Sodium hydroxide in Methanol and Methylene dichloride solvent media to gives Mirtazapine.
159
ANNEXURE - IX
Flow Chart
1-Methyl-3-phenylpiperazine
2-Chloronicotinonitrile
Potassium Fluoride Sol.Recovery
Stage I
Butanol Organic Residue
Potassium Hydroxide Process Emissions
Toluene
Water
Vitride (40%) in Toluene Evaporation Loss
Stage II
Toluene Effluent
n-Hexane Organic Residue
Sulfuric acid Evaporation Loss
Sodium Hydroxide (50%) Effluent
Stage III
Methanol Spent Carbon
Carbon
Hyflow
Mirtazapine
160
ANNEXURE - IX
PRODUCT : Tigecycline
Description :
Stage-1 : : Minocycline Hydrochloride reacts with Nitric acid then undergoes reduction with Hydrogen gas in
presence of Palladium carbon finally salt formation with Sulfuric acid in Methanol, Isopropyl Alcohol and sec
Butanol solvent media to get Stage-1 compound.
Stage-2 : t-Butyl bromoacetate reacts with t-Butylamine in Toluene solvent media then react with Hydrogen
chloride gas in Isopropyl alcohol solvent media to get Stage-2 compound.
Stage-3 : The Stage-2 compound undergoes chlorination using Phosphorus Pentachloride in presence of
Dimethylformamide in Toluene solvent media to get Stage-3 compound.
Stage-4 : The Stage-1 compound reacts with Stage-3 compound in presence of Sodium hydroxide in Acetone,
Methylene dichloride and Methanol solvent media to get Tigecycline.
161
ANNEXURE - IX
Flow Chart
Minocycline Hydrochloride
Sulfuric acid Sol.Recovery
Nitric acid Evaporation Loss
Methanol Stage I Inorganic Solid Waste
Palladium Carbon
sec -Butanol
t -Butyl bromoacetate
t -Butylamine Sol.Recovery
Hydrogen Chloride Stage II Organic Residue
Dimethylformamide Stage III Organic Residue
Phosphorus Pentachloride Inorganic Solid Waste
Process Emissions
Stage-1
Acetone Effluent
Carbon Stage IV Organic Residue
Hyflow Spent Carbon
Methanol
Water
Tigecycline
162
ANNEXURE - IX
PRODUCT : Efinaconazole
Description :
Stage-1 : : Methyi-(R)-Iactate condensation with Morpholine and Dihydropyran in presence of Sodium methoxide
and Methane sulfonic acid in Methyl tert-butyl ether and Tetrahydrofuran solvent media to gives (2R)-1- Morpholino-
2-(tetrahydro-2H-pyran-2-yloxy)propan-1-one (Stage-1) compound.
Stage-2 : (2R)-1-Morpholino-2-(tetrahydro-2H-pyran-2-yloxy)propan-1-one (Stage-1) condensation with 1-
Bromo-2,4-difluoro benzenene in presence of Magnesium, Tetrahydrofuran, Ethyl acetate and acetic acid to
gives (2R)-1-(2,4-Difluorophenyl)-2-(tetrahydro-2H-pyran-2-yloxy)propan-1-one (Stage-2) compound.
Stage-3 : (2R)-1-(2,4-Difluorophenyl)-2-(tetrahydro-2H-pyran-2-yloxy)propan-1-one (Stage-2) reacts with
Trimethyl sulfaxonium iodied and further condensation with Triazole in presence of Sodium ter-butoxide,
Tetrahydrofuran and Dimethylformamide and further deprotection then salt formation with Methanesulfonic acid in
Methanol to gives (2R,3R)-2-(2,4-Difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butane-2,3-diol methanesulfonate (Stage-
3) compound.
Stage-4 : : (2R,3R)-2-(2,4-Difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butane-2,3-diol methanesulfonate (Stage-3)
further reacts with Methansulfonyl chloride in presence of Triethylamine, Ethyl acetate, Sodium methoxide in
Methanol to gives 1-(((2R,3S)-2-(2,4-Difluorophenyl)-3-methyloxiran-2-yl) methyl)-1H-1,2,4-triazole (Stage-4)
compound.
Stage-5 : 1-(((2R,3S)-2-(2,4-Difluorophenyl)-3-methyloxiran-2-yl)methyl)-1H-1,2,4-triazole (Stage-4) on
condensation with 4-Methylene piperidine hydrochloride in presence of Lithium hydroxide in Acetonitrile media to
gives (2R,3R)-2-(2,4-Difluorophenyl)-3-(4-methylenepiperidin-1-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol and further
reacts with p-Toluenesulfonic acid in presence of Isopropyl Alcohol to gives Efinaconazole Tosylate (Stage-5)
compound.
Stage-6 : Efinaconazole Tosyrate (Stage-S) further purification inpresence of water, Sodium hydroxide, Ethyl
acetate and n-Heptane to gives Efinaconazole.
163
ANNEXURE - IX
Flow Chart
Methyl-(R)-Lactate
Morpholine Sol.Recovery
Sodium Methoxide Evaporation Loss
Methyl tert-butyl ether Effluent
Stage I
Dihydropyran Organic Residue
Tetrahydrofuran
Methansulfonic acid
Water
Stage-1
Magnesium turnings Sol.Recovery
1-Bromo-2,4-difluorobenzenene Evaporation Loss
Stage II
Sodium chloride 10%solution
Water
Stage-2
Trimethyl sulfoxonium iodide
Triazole
Sodium tert-butoxide
Methanesulfonic acid Sol.Recovery
Tetrahydrofuran Evaporation Loss
Ethyl Acetate Stage III Effluent
Isopropyl Acetate Inorganic Solid Waste
Methanol
Sodium Chloride (10%) solution
Sodium Sulfate
Water
Stage-3
Methansulfonyl chloride
Sodium Methoxide Evaporation Loss
Stage IV
n-Hexane
Water
Stage-4
4-Methylene piperdine Hydrochloride
Lithium Hydroxide Sol.Recovery
p-Toluenesulfonic acid Stage V Evaporation Loss
Acetonitrile Effluent
Isopropyl Alcohol
Water
Efinaconazole Tosylate Sol.Recovery

n-Heptane Stage VI Organic Residue
Water
Efinaconazole
164
ANNEXURE - IX
PRODUCT : Cetirizine Dihydrochloride
Description :
Stage-1 : p -Chloro Benzophenone reacts with Sodium Borohydride in presence of Methanol solvent medium gives
p -Chloro benzhydrol.
Stage-2 : p -Chloro Benzhydrol react with Hydrochloric Acid in presence of Toluene solvent medium produces p
Chloro Benzhydryl chloride.
Stage-3 : p -Chloro Benzhydryl chloride reacts with piperazine in presence of Toluene solvent medium gives p
Chloro Benzhydryl Piperazine.
Stage-4 : p -Chloro Benzhydryl Piperazine reacts with 2-Chloro Ethanol in presence of Triethylamine in Toluene
solvent medium to get p -Chloro Benzhydryl Piperazine ethanol.
Stage-5 : p -Chloro Benzhydryl Piperazine ethanol it is further react with Sodium Monochloro Acetate in presence of
Potassium Hydroxide in Dimethyl Formamide solvent forms Ceterizine Base. Ceterizine Base reacts with
Hydrochloric acid gives Cetirizine Dihydrochloride.
165
ANNEXURE - IX
Flow Chart
P-Chloro Benzophenone Sol.Recovery
Stage I
Methanol Effluent
Stage II
Toluene Effluent
Piperazine Evaporation Loss
Toluene Stage III Effluent
Process Emissions
Stage-3
2-Chloroethanol Sol.Recovery
Toluene Stage IV Effluent
Dimethyalformamide Organic Residue
Water Inorganic Residue
Sodium Sulfate
Stage-4
Dimethylformamide Sol.Recovery
Sodium Monochloro Acetate Evaporation Loss
Potassium Hydroxide Stage V Effluent
Carbon Spent Carbon
Water
Cetirizine Dihydrochloride
166
ANNEXURE - IX
PRODUCT : Lomitapide Mesylate
Description :
Stage-1 : To a solution of 9H-Fluorene-9-carboxylic acid in Tetrahydrofuran, N-Butyllithium was added at 0°C
and maintained for 2 hrs. The resulting reaction mass was added with 1,4-Dibromobutane. The reaction
maintained for 4-5 hrs at same temperature in presence of Hydrochloric acid and quenched with water. The
aqueous layer extracted with Methylene Dichloride and the separated organic layer concentrated to yield Stage-1
Compound.
Stage-2 : To a solution of Satge-1 Compound in Methylene Dichloride, Oxalyl Chloride was added at 0°C and
maintained for 2 hrs. The resulting reaction mass concentrated and the residue dissolved in Methylene
Dichloride. This reaction crude was added to a solution of 2,2,2-Trifluoroethylamine in presence of Sodium
Bicarbonate and Hydrochloric acid using Cyclohexane as solvent medium. The reaction maintained for 4-5 hrs
and quenched with water. The seperated organic layer is concentrated to get Stage-2 Intermediate.
Stage-3 : To a solution of Stage-2 Intermediate in Dimethylformamide, Potassium Carbonate was added.
Piperidin-4-amine was added to mass and the mixture was stirred for 8hrs at 65°C. The reaction mixture was
added with Cyclohexane and Methylene Dichloride as solvent media at room temperature, the separated organic
layer is concentrated to yield Stage-3 Material.
Stage-4 : Oxalyl Chloride was slowly added to a solution of 4'-(Trifluoromethyl)biphenyl-2-carboxylic acid in
Methylene Dichloride at 0°C. Reaction mass was stirred at room temperature for 60 min. The reaction mass is
concentrated and dissolved in Methylene Dichloride. The resulted reaction mass was added to Triethylamine and
Stage-3 Material solution at 0°C, and maintained at room temperature for over night. The reaction mass was
treated with Hydrochloric acid solution in presence of and the separated aqueous layer was basified with Sodium
Bicarbonate. The reaction mixture was extracted with Methylene Dichloride and concentrated under vacuum to
produce Lomitapide.
Stage-5 : To a solution of Lomitapide in Ethyl Acetate was treated with Methanesulfonic acid at ambient
condition. The reaction mass was stirred for 8-10 hrs at the same temperature and filtered off to yield Lomitapide
Mesylate as final product.
167
ANNEXURE - IX
Flow Chart
9H-Fluorene-9-carboxylic acid
1,4-Dibromobutane Sol.Recovery
n-Butyllithium (20%) in Hexane Evaporation Loss
Tetrahydrofuran Stage I Effluent
Hydrochloric acid (35%) Process Emissions
Water
Stage-1
2,2,2-Trifloroethylamine
Oxalyl Chloride Sol.Recovery
Cyclohexane Process Emissions
Sodium Bicarbonate
Water
Stage-2
Piperidin-4-amine Sol.Recovery
Dimethylformamide Stage III Effluent
Cyclohexane Organic Residue
Methylene Dichloride Process Emissions
Water
Stage-3
4'-(Trifluoromethyl)biphenyl-2-
carboxylic acid Sol.Recovery
Oxalyl Chloride Evaporation Loss
Triethylamine Stage IV Effluent
Sodium Bicarbonate Organic Residue
Methylene Dichloride Process Emissions
Water
Lomitapide Sol.Recovery
Methanesulfonic acid Stage V Evaporation Loss
Lomitapide Mesylate
168
ANNEXURE - IX
PRODUCT : Ospemifene
Description :
Stage-1 : 4-Hydroxybenzophenone on condensation with 3-Chloro-1-phenylpropan-1-one in presence of
Titanium Tetrachloride, Zinc dust and Potassium Carbonate using Tetrahydrofuran as asolvent medium to give
Stage-1 Compound.
Stage-2 : Stage-1 Compound on condensation with 2-Bromoethanol in presence of Potassium Carbonate using
Methanol as solvent medium to form Ospemifene.
Flow Chart
4-Hydroxybenzophenone
3-Chloro-1-phenylpropan-1-one Sol.Recovery
Titanium Tetrachloride Evaporation Loss
Zinc Dust Stage I Effluent
Potassium Carbonate Inorgainc Solid Waste
2-Bromoethanol Evaporation Loss
Potassium Carbonate Stage II Effluent
Ospemifene
169
ANNEXURE - IX
PRODUCT : Lumacaftor
Description :
Stage-1 : 2-Amino-5-methylpyridine on condensation with Pivaloyl Chloride in presence of Triethylamine and

Sodium Sulfate using Methylene Dichloride as solvent medium to give Stage-1 Compound.
Stage-2 : Stage-1 Compound on reaction with Hydrogen Peroxide in presence of Sodium Sulfate using Acetic
acid and Methylene Dichloride as solvent media to get Stage-2 Intermediate.
Stage-3 : Stage-2 Intermediate on reaction with Phosphorous Oxychloride in presence of Triethylamine using
Methylene Dichloride as solvent medium to form Stage-3 Material.
Stage-4 : Stage-3 Material on hydrolysis with Hydrochloric acid in presence of a base Sodium Bicarbonate using
Methylene Dichloride as solvent medium to yield Stage-4 Compound.
Stage-5 : Stage-4 Compound on condensation with 1-(2,2-Difluorobenzo[d][1,3] dioxol-5-yl) cyclopropane

carbonyl chloride in presence of Triethylamine using Methylene Dichloride as a solvent medium to produce Stage-
5 Intermediate.
Stage-6 : Stage-5 Intermediate on condensation with 3-Boronobenzoic acid in presence of catalyst Pd(dppf)Cl2
and Triethylamine using Dimethylformamide and Methanol as solvent media to obtain Lumacaftor.
170
ANNEXURE - IX
Flow Chart
2-Amino-5-methylpyridine
Pivaloyl Chloride Evaporation Loss
Stage I
Sodium Sulfate Organic Residue
Water
Stage-1
Acetic acid Sol.Recovery
Hydrogen Peroxide (50%) Evaporation Loss
Stage II
Sodium Sulfate Organic Residue
Water
Phosphorous Oxychloride Evaporation Loss
Triethylamine Stage III Effluent
Sodium Bicarbonate Stage IV Effluent
Stage-4
1-(2,2-Difluorobenzo[d][1,3]
dioxol-5-yl) cyclopropane Sol.Recovery
carbonyl chloride Stage V Evaporation Loss
Water
Stage-5
3-Boronobenzoic acid
Pd(dppf)Cl2 Stage VI Evaporation Loss
Dimethylformamide Effluent
Water
Lumacaftor
171
ANNEXURE - IX
PRODUCT : Canagliflozin
Description :
Stage-1 : A suspension of Gluconolacotone in Methylene Dichloride was charged to reactor and N-Methyl
morpholine followed by Trimethylsilyl Chloride was added. Reaction mass was stirred at room temp for 10 hrs. After
the reaction completed water was added and the organic layer separated. The organic layer was distilled off in
presence of Touene as slvent medium to get Stage-1 Compound.
Stage-2 : A solution of Stage-1 Compound in Tetrahydrofuran was charged in to the reactor. 2-(5-Bromo-2-methyl
benzyl)-5-(4-fluorophenyl)thiophene was charged and stirred to dissolve completely. The reaction mass was cooled
to -70oC and n-Butyllithium was added. Reaction mass maintained for two hrs and then quenched with Ammonium
Chloride solution in presence of Sodium Bicarbonate using Toluene as solvent medium. After raising the reaction
mass temp to room temp followed by usual workup, the Stage-2 Material was isolated from Cyclohexane.
Stage-3 : A solution of Stage-2 Material in Methanol was charged into to the reactor and Methanesulfonic acid was
added to it. The reaction maintained for 16hrs at room temperature and then poured in to the ice water. The reaction
mass extracted with Cyclohexane and concentrated in presence of Sodium Bicarbonate and Sodium Chloride using
Ethyl Acetate as solvent medium to give Stage-3 Intermediate.
Stage-4 : A solution of Stage-3 Intermediate in Methylene Dichloride was charged into the reactor and then
Acetonitrile was added. The reaction mass cooled to -5oC and Triethylsilane was added slowly in presence of Boran
trifloride etharate, Sodium Bicarbonate and Sodium Chloride. After two hrs of maintainance, reaction mass poured
into ice water and organic layer separated. The organic layer was distilled and the product Canagliflozin was
isolated from Cyclohexane. The product was dried at 50oC for 5hrs and then packed as Canagliflozin.
172
ANNEXURE - IX
Flow Chart
Gluconolacotone
Trimethylsilyl Chloride
N-Methylmorpholine Sol.Recovery
Stage I
Toluene Effluent
Sodium Dihydrogen Phosphate Organic Residue
Sodium Chloride
Water
Stage-1
2-(5-Bromo-2-methylbenzyl)-5-
(4-fluorophenyl)thiophene
n-Butyllithium (20%) in Hexane
Toluene Sol.Recovery
Tetrahydrofuran Evaporation Loss
Stage II
Hydrogen Effluent
Palladium Carbon Organic Residue
Ammonium Chloride
Cyclohexane
Water
Stage-2
Methanesulfonic acid
Stage III
Sodium Bicarbonate Effluent
Sodium Chloride Organic Residue
Cyclohexane Process Emissions
Water
Stage-3
Triethylsilane
Boran trifloride etharate Sol.Recovery
Acetonitrile Evaporation Loss
Methylene Dichloride Stage IV Effluent
Sodium Chloride Process Emissions
Cyclohexane
Water
Canagliflozin
173
ANNEXURE - IX
PRODUCT : (S)-2-(tert-Butoxycarbonylamino)-3-(4-carbamoyl-2,6-
dimethylphenyl)propanoic acid
Description :
Stage-1 : (Z)-Methyl 2-(tert-Butoxycarbonyl amino)-3-(4-carbamoyl-2,6-dimethylphenyl)acrylate undergoes
reduction with Hydrogen in presence of a catalyst Rh(cod)(r r-dipamp)bf4 using Methanol as solvent medium to get
Stage-1 Compound.
Stage-2 : Stage-1 Compound undergoes hydrolysis with Lithium Hydroxide in presence of Hydrochloric acid using
Tetrahydrofuran as solvent medium to form (S)-2-(tert-Butoxycarbonylamino)-3-(4-carbamoyl-2,6-dimethyl
phenyl)propanoic acid.
Flow Chart
(Z)-Methyl 2-(tert-Butoxycarbonyl
amino)-3-(4-carbamoyl-2,6- Sol.Recovery
dimethylphenyl)acrylate Evaporation Loss
Stage I
Rh(cod)(r r-dipamp)bf4 Process Emissions
Methanol
Stage-1
Lithium Hydroxide Sol.Recovery
Tetrahydrofuran Stage II Evaporation Loss
(S)-2-(tert-Butoxycarbonylamino)-3-(4-carbamoyl-2,6-dimethylphenyl)propanoic acid
174
ANNEXURE - IX
PRODUCT : Empagliflozin
Description :
Stage-1 : Condensation of (4-(5-Bromo-2-chlorobenzyl) phenoxy)(tert-butyl) dimethyl silane with 3,4,5-

tris(trimethylsilyloxy)-6-((trimethylsilyloxy)methyl) tetrahydro-2Hpyran-2-one in presence of n-Butyllithium in Hexane,
further reaction with Methanesulfonic acid using Methanol and Tetrahydrofuran as solvent media to get Stage-1
Cmpound.
Stage-2 : A solution of Stage-1 Compound in Methylene Dichloride was charged into the reactor and then
Acetonitrile was added. The reaction mass cooled to -5oC and Triethylsilane was added slowly in presence of Boran
trifloride etharate, Sodium Bicarbonate and Sodium Chloride. After two hrs of maintainance, reaction mass poured
into ice water and organic layer separated. The organic layer was distilled and the product Stage-2 Intrermediate
was isolated from Cyclohexane. The product was dried at 50oC for 5hrs and then packed as Stage-2 Intrermediate.
Stage-3 : Stage-2 Intrermediate on condensation with (R)-Tetrahydrofuran-3-yl 4-methylbenzenesulfonate in

presence of Caesium Carbonate using Dimethylformamide as solvent medium to form Empagliflozin.
Flow Chart
(4-(5-Bromo-2-chlorobenzyl)
phenoxy)(tert-butyl) dimethyl
silane
3,4,5-tris(trimethylsilyloxy)-6- Sol.Recovery
((trimethylsilyloxy)methyl) Evaporation Loss
tetrahydro-2Hpyran-2-one Stage I Effluent
n-Butyllithium (20%) in Hexane Organic Residue
Methanesulfonic acid Process Emissions
Methanol
Tetrahydrofuran
Water
Stage-1
Triethylsilane
Boran trifloride etharate Sol.Recovery
Acetonitrile Evaporation Loss
Methylene Dichloride Stage II Effluent
Sodium Chloride Process Emissions
Cyclohexane
Water
Stage-2
Caesium Carbonate Sol.Recovery
(R)-Tetrahydrofuran-3-yl 4- Evaporation Loss
methylbenzenesulfonate Stage III
Effluent
Empagliflozin
175
PRODUCED BY AN AUTODESK EDUCATIONAL PRODUCT ANNEXURE - X
N
PRODUCED BY AN AUTODESK EDUCATIONAL PRODUCT

OAD
B.T R
TING
EXIS
OAD
.T R
GB
TIN
EXIS
R
TRANSFORME
EXISTING B.T ROAD

ROAD
EXISTING B.T
176
ANNEXURE - XI
LIST OF HAZARDOUS RAW MATERIALS

Hazardous Raw Materials
1,4-Dioxane Methane Sulfonic aicd
Acetic acid Methanesulfonic acid
Acetic Anhydride Methanol
Acetone Methansulfonic acid
Acetonitrile Methyl Iodide
Aluminium Chloride Methyl tert-butyl ether
Ammonia (25%) Solution Methylamine (40%)
Ammonia gas Methylene Dichloride
Ammonium Chloride Morpholine
Aniline N,N-Dimethylformamide
Anisole n-Heptane
Benzaldehyde Nitric acid
Benzene Nitric acid (70%)
Chloroform Phosphoric acid
Chlorosulfonic acid Phosphorous Oxychloride
Cyclohexane Phosphorus Pentachloride
Dimethylamine Piperazine
Dimethylamine (40%) Potassium Hydroxide
Dimethylformamide Potassium Iodide
Dimethylsulfate Sodium Azide
Ethanol Sodium Bicarbonate
Ethyl Acelate Sodium Borohydride
Ferric Chloride Sodium Hydroxide
Fluorobenzaldehyde Sodium Hydroxide (50%)
Formaldehyde (35%) Sodium Methoxide
Fumaric acid Sodium Nitrite
Heptane Sodium Sulfate
Hydrochloric acid (35%) Stannous Chloride dihydrate
Hydrogen t -Butylamine
Hydrogen Bromide tert-Butanol
Hydrogen Chloride Tetrahydrofuran
Hydrogen Peroxide (50%) Thiourea
Hydroxylamine Hydrochloride Titanium Tetrachloride
Isopropyl Acetate Toluene
Liq.Ammonia (20%) Triethylamine
Maleic acid Xylene
Maleic Anhydride
177
ANNEXURE - XII

LIST OF RAW MATERIALS
Consumption of
Daily
Raw Material /
Raw Material Consumption of
Batch of
Raw Material
Product
Kg Kg
2-Methyl-2-Butanone = 54 40.5
Acetone = 280 210
Aniline = 54 40.5
Benzaldehyde = 55 41.3
Calcium Acetate = 30.18 22.6
Carbon = 8 6
Dimethyl Cabonate = 54 40.5
Fluorobenzaldehyde = 58 43.5
Hydrogen = 2 1.5
Hyflo = 31 23
Isopropyl Alcohol = 1440 1080
Methanol = 2030 1523
Palladium Carbon = 13 9.8
Potassium Carbonate = 6 4.5
p -Toluenesulfonic acid = 4 3
Sulfuric acid = 6.5 4.9
tert-Butyl-2-[(4R,6S)-6-(cyano methyl)-2,2-
= 133 99.8
dimethyl-1,3-dioxan-4-yl] acetate
Toluene = 440 330
PRODUCT : Telmisartan
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
4-Methyl-6-(1-methyl benzimidazol-2-yl)-2-
= 96 96
propyl-1H-benzimidazole
Acetic acid = 51 51
Acetone = 580 580
Acetonitrile = 1260 1260
Activated Carbon = 6 6
Ammonia (25%) Solution = 24 24
Ethanol = 900 900
Hydrogen Bromide = 26 26
Hyflo = 10 10
Methanol = 480 480
Methyl 2-[4-(bromomethyl)
= 98 98
phenyl]benzoate
Potassium Hydroxide = 55 55
178
ANNEXURE - XII
PRODUCT : Zolmitriptan
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
Acetic acid = 14 1.7
Acetone = 800 96
Ethyl Acetate = 800 96
Hydrochloric acid (35%) = 24 2.9
Methyl Iodide = 144 17.3
Methyl-3-(2-aminoethyl)-5-{(2-oxozolidin-4-
= 80 9.6
yl)methyl)-1H-indole-2-carboxylate
Sodium Hydroxide = 20 2.4

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
1-(2,5-Difluoro-4-(3-methylpiperzin-1-yl)
= 126 26.5
phenyl) ethanone Hydrochloride
2,4-Difluoroaniline = 40 8.4
Acetic Anhydride = 118 24.8
Cyclohexane = 760 159.6
Diethyl Carbonate = 800 168
Diethyl Ether = 1000 210
Di-tert-butyldicarbonate = 96 20.2
Ethanol = 670 140.7
Methylene Dichloride = 1800 378
Phosphoric acid = 70 14.7
Sodium Bicarbonate = 60 12.6
Sodium Chloride = 100 21
Sodium Hydride (60%) = 22 4.6
Tetrahydrofuran = 1200 252
Toluene = 1200 252
Triethyl Orthoformate = 86 18.1
Triethylamine = 182 38.2
179
ANNEXURE - XII
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
(1R,5S,6R)-3-benzyl-6-nitro-3-
= 102 21.4
azabicyclo[3.1.0]hexane-2,4-dione
7-Chloro-1-(2,4-difluorophenyl)-6-fluoro-4-
oxo-1,4-dihydro-1,8-naphayridine-3- = 100 21
carboxylic acid
Acetonitrile = 520 109.2
Benzaldehyde = 34 7.1
Boran trifluoride Tetrahydrofuran Complex = 130 27.3
Hydrogen = 6 1.3
Isopropyl Alcohol = 780 163.8
Sodium Borohydride = 106 22.3
Toluene = 950 199.5
PRODUCT : Selegiline Hydrochloride

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
Acetic acid = 50 12
Ethanolic Hydrochloric acid (37%) = 144 34.6
N-Methyl-1-phenylpropane-2-amine-d-
= 208 49.9
tartarate
Propargyl Bromide = 84 20.2
Toluene = 1040 249.6
180
ANNEXURE - XII
PRODUCT : Safinamide
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
1-(Bromomethyl)-3-fluorobenzene = 78 16.4
2-Aminopropanamide = 34 7.1
3-(Bromomethyl) phenol = 78 16.4
Methylene Dichloride = 540 113.4
Sodium Carbonate = 38 8.0
Toluene = 780 163.8
PRODUCT : Landiolol
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
(S)-2-(Bromomethyl) oxirane = 30 3.6
(S)-4-(Chloromethyl)-2,2-dimethyl-1,3-
= 32 3.8
dioxolane
3-(4-Hydroxyphenyl)propanoic acid = 28 3.4
Acetone = 160 19.2
Dimethyl Sulfoxide = 140 16.8
Ethyl Acetate = 200 24.0
Methanol = 80 9.6
N-(2-Aminoethyl)morpholine-4-
= 40 4.8
carboxamide
Potassium Iodide = 1 0.1
Toluene = 380 45.6
181
ANNEXURE - XII

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
2,4,5-Trifluorobenzyl-α-amino acid = 120 57.60
2-Chloro Pyrazine = 50 24
Carbo benzyloxychloride = 500 240
Diazomethane in Diethyl ether (40%) = 40 19.2
Dimethylformamide = 785 376.8
Hydrazine Hydrate = 23 11.04
Hydrogen = 2 0.96
Hydrogen Chloride = 16 7.68
Isobutyl Chloroformate = 440 211.2
Methanol = 2980 1430.4
Methanolic Hydrochloride (20%) = 60 28.8
Polyphosphoric Acid = 40 19.2
Silver benzoate = 738 354.24
Triethyl orthoester = 88 42.24

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
1,3-Dicyclohexyl carbodiimide = 93.5 4.68
Acetone = 900 45.0
Benzyl Alcohol = 36.5 1.83
Carbon = 5 0.25
Ethanol = 17 0.85
Hydrogen = 5 0.25
Hyflo = 6.5 0.33
Indole carboxylic acid = 55 2.75
Mandelic Acid = 50 2.50
Methanol = 1350 67.5
Norvaline = 17 0.85
Pyruvic Acid = 12 0.60
Rhodium on Carbon = 0.5 0.03
Sulfuric Acid = 0.5 0.03
tert-Butylamine = 8.8 0.44
Toluene = 2750 137.50
182
ANNEXURE - XII
PRODUCT : Cangrelor
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
1,4-Dioxane = 90 8.64
2-(Acetoxyethyl)-5-(6-chloro-2-mercapto-
9H-purin-9-yl) tetrahydrofuran-3,4-diyl = 33 3.17
diacetate
2-(Methylthio) ethanamine = 6 0.58
3-Chloro-1,1,1-trifluoro propane = 10 0.96
Dichloromethylene diphosphonic acid = 14 1.34
Phosphorous Oxychloride = 8 0.77
Sodium Sulfate = 3.5 0.34
Tributylamines = 5 0.48
Triethyl Phosphate = 11 1.06
PRODUCT : Cilomilast
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
1-( 3-(Cyclopentyloxy)-4-methoxyphenyl)-4-
= 34 3.26
oxocyclohexane carbonitrile
1,3-Dithian-2-one = 17 1.63
Ammonium Chloride = 7 0.67
Titanium Tetrachloride = 21 2.02
Zinc Chloride = 12 1.15
183
ANNEXURE - XII
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
(S)-tert-Butyl-5-azaspiro[2,4]-heptan-7-yl-
= 30 2.88
carbamate
8-Chloro-6,7-difluoro-1-((1S,2S)-2-
fluorocycloproyl)-4-oxo-1,4- = 33 3.17
dihydroquinoline-3-carboxylic acid
Anisole = 90 8.64
Chloroform = 265 25.44
Ethanol = 90 8.64
Sodium Hydroxide = 4.5 0.43
Sodium Sulfate = 3.5 0.34
Trifluoroacetic acid = 450 43.20
PRODUCT : Formoterol Fumarate

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
Fumaric acid = 4 0.36
Hydrogen = 2 0.18
N-(2-(benzyloxy)-5-(oxiran-2-yl)phenyl)
= 21 1.89
formamide
N-benzyl-1-(4-methoxyphenyl)propan-2- = 20 1.80
184
ANNEXURE - XII

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
2,3-Dichlorobenzaldehyde = 16 3.84
Acetone = 25 6.00
Ammonium Acetate = 8 1.92
Chloromethyl Butyrate = 34 8.16
Methanol = 500 120
Methyl Acetoacetate = 22 5.28
Potassium Hydroxide = 9 2.16
Toluene = 75 18
PRODUCT : Udenafil
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
2-(1-Methylpyrrolidin-2-yl) ethanamine = 11 2.64
2,4,6-Trichlorobenzoyl chloride = 0.5 0.12
4-Amino-1-methyl-3-propyl-1H-pyrazole-5-
= 13 3.12
carboxamide
5-(Chlorosulfonyl)-2-propoxybenzoic acid = 23 5.52
Acetone = 115 27.6
Metthylene Dichloride = 250 60
Potassium tert-butoxide = 7 1.68
tert-Butanol = 220 52.8
185
ANNEXURE - XII
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
2-[(tert-Butoxycarbonyl)amino] -5-
= 29 6.96
(nitrocarbamimidamido) pentanoic acid
Chloroform = 200 48
Citric acid = 11 2.64
Diethyl Ether = 130 31.2
Ethanol = 70 16.8
Ethyl(2R,4R)-4-methyl piperidine-2-
= 16 3.84
carboxylate
Hydrogen gas = 0.5 0.12
Isobutyl chloroformate = 13 3.12
Palladium Carbon = 5.5 1.32
Sodium Chloride = 35 8.4
Sodium Hydroxide (20%) = 20 4.8
Tetrahydrofuran = 120 28.8
Triethylamine = 25 6
Ttetrahydroquinoline-8-sulfonyl chloriode = 18 4.32
PRODUCT : Balofloxacin
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
1-Cyclopropyl-6,7-difluoro-8-methoxy-4-
= 57 13.68
oxo-1,4-dihydro quinolin-3-carboxylic acid
N-Methylpiperidine-3-amine
= 45 10.8
Dihydrochloride
186
ANNEXURE - XII
PRODUCT : Beraprost
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
Diisopropyl Ether = 25 6
Dimethoxyethane = 10 2.4
Dimethyl(3-methyl-2-oxo-hept-5-yn-1-
= 33 7.92
yl)phosphate
Dimethylformamide = 50 12
Methanol = 220 52.8
Methyl-4-(2-acetoxy-1-formyl-2,3,3a,8b-
tetrahydro-1H-benzo[b]cyclopenta[d]furan- = 35 8.4
5-yl)butanoate
Pentane = 28 6.72
Sodium Hydride (60%) = 4.5 1.08
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
Acetic anhydride = 20 4.80
Chloroform = 4 0.96
Dimethyl Sulfoxide = 300 72
Ethanol = 455 109.2
Ethyl-3-(4-(1-acetamido cyclo propyl)-2,3,5-
= 52 12.48
trifluorophenyl)-3-oxopropanoate
N,N-Dimethylformamide = 23 5.52
S-(2)-Aminopropanol = 12 2.88
187
ANNEXURE - XII
PRODUCT : Talipexole
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
3-Chloropropan-1-ene = 13 3.1
Acetic acid = 8.5 2.0
Azapane-4-one = 18 4.3
Bromine = 22 5.3
Thiourea = 11 2.6
Toluene = 180 43.2
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
4-Chlorobutyraldehyde Sodium Bisulfite
= 84 5.0
adduct
4-Nitrobenzyl bromide = 150 9.0
Carbon = 18 1.1
Disodium Hydrogen Phosphate = 14 0.8
Ferric Chloride = 10 0.6
Formaldehyde (35%) = 90 5.4
Hydrazine Hydrate (50%) = 100 6.0
Hyflo = 15 0.9
Methanol = 2425 145.5
Pyrrolidine = 50 3.0
Sodium Nitrite = 35 2.1
Sodium Sulfite = 110 6.6
Stannous Chloride dihydrate = 220 13.2
Toluene = 1650 99.0
Vaccum Salt = 15 0.9
188
ANNEXURE - XII

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
(4-4-Diethoxybutyl) dimethylamine = 65 3.9
4-Amino-1,2,4-Triazole = 48 2.9
4-Nitrobenzyl bromide = 117 7.0
Acetone = 500 30.0
Ammonia Solution (20%) = 150 9.0
Benzoic Acid = 35 2.1
Carbon = 11 0.7
Ferric Chloride = 6 0.4
Hydrazine Hydrate (50%) = 80 4.8
Hydrochloric Acid (35%) = 361 21.7
Methanol = 865 51.9
Sodium Nitrite = 66 4.0
Stannous Chloride Dihydrate = 177 10.6
Sulfuric Acid = 50 3.0
Toluene = 350 21.0
Vaccum Salt = 35 2.1
PRODUCT : Imipenem
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
2-Aminoethanethiol Hydrochloride = 31 7.44
4-(Dimethylamino) pyridine = 0.5 0.12
4-Nitrobenzyl-6-(1-hydroxy ethyl)-3,7-
dioxoazabicyclo [3.2.0]heptane-2- = 91 21.84
carboxylate
Benzylformimidate Hydrochloride = 52 12.48
Diisopropylamine = 70 16.80
Diphenyl chlorophosphate = 77 18.48
Heptane = 390 93.60
Hydrogen = 1 0.24
N,N-Dimethylacetamide = 10 2.40
189
ANNEXURE - XII
PRODUCT : Cefixime
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
(Z)-4-Chloro-2-[[(2-methoxy
= 78 9.36
carbonyl)methoxy]imino]-acetoacetate
2,2-Dithio bis (benzothiazole) = 100 12.0
7-Amino-8-oxo-3-vinyl-5-thia-1-
azabicyclo[4.2.0]oct-2-ene-2-carboxylic = 56 6.72
acid
Carbon = 5 0.6
Ethylene Diamine Tetraacetic acid = 0.5 0.06
Hyflo = 5 0.6
Methanol = 420 50.4
Sodium Acetate = 94 11.28
Sodium Hydroxide = 25 3
Thiourea = 32 3.84
Triphenylphosphine = 80 9.6
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
1-Methyl-1H-tetrazole-5-thiol = 29 3.48
2-[(Cyanomethyl)thio] acetylchloride = 86 10.32
7-Amino-7-methoxycepholo sporanic acid
= 153 18.36
benzhydryl ester
Acetone = 1000 120.00
Anisole = 26 3.12
Diisopropyl ether = 305 36.60
Trifluoro acetic acid = 50 6.00
190
ANNEXURE - XII
PRODUCT : Iloprost
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
[1'[(E)-4-Methyl-3-oxo-octo-1-en-6-
ynyl]spiro[1,3-dioxalane-2,5'-2,3,3a,4,6,6a- = 77 18.5
hexahydro-1H-pentalene]-2'-yl]benzoate
5-(Triphenylphosphoranyl idene)
= 56.5 13.6
pentanoic acid
Dimethyl Sulfoxide = 350 84.0
Methanol = 6 1.4
p -Toluene Sulfonic acid = 31 7.4
Tetrahydropyranyl methyl ether = 43 10.3
PRODUCT : Aripiprazole
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
1,4-Dibromobutane = 160 112.0
2,3-Dichlorophenyl Piperazine
= 45 31.5
Hydrochloride
7-Hydroxy carbostyril = 40 28.0
Acetone = 200 140.0
Carbon = 6 4.2
Hyflo = 10 7.0
Toluene = 180 126.0
191
ANNEXURE - XII
PRODUCT : Brivaracetam
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
4-N-Propylhydroxy furanone = 50 21.0
5-2-Aminobutyramide = 36 15.1
Ammoniumformate = 18 7.6
Diisopropyl Ether = 360 151.2
Toluene = 200 84.0

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
1,4-Dioxane = 140 58.8
2-Chloro phenylacetic acid = 70 29.4
4-Chlorophenol = 41 17.2
Aluminium Chloride = 27 11.3
Dicyclohexylcarbodiimide = 85 35.7
Lithium Aluminium Hydride = 27 11.3
Magnesium Turnings = 6 2.5
Maleic acid = 23 9.7
Methanol = 70 29.4
Phosphoric acid = 28 11.8
Phosphorous Pentaoxide = 42 17.6
Potassium tert-Butaoxide = 50 21.0
Savcosine methyl ester Hydrochloride = 58 24.4
Toluene = 360 151.2
192
ANNEXURE - XII
PRODUCT : Ramipril
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
Acetic Anhydride = 79 3.6
Acetone = 530 23.9
Benzylalcohol = 225 10.1
Cyclopentanone = 62 2.8
ECPP Alanine = 155 7.0
Hydrogen = 3 0.1
Hyflo = 8.2 0.4
L-Serine methylester Hydrochloride = 120 5.4
Palladium Carbon = 5.8 0.3
Para Toluene sulfonic acid = 10 0.5
Toluene = 3600 162.0
Xylene = 600 27.0
193
ANNEXURE - XII
PRODUCT : Zileuton
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
2-Acetylbenzo[b]thiophene = 90 37.8
Carbon = 3 1.3
Liq.Ammonia (20%) = 124 52.1
Methanol = 1300 546.0
N-Hydroxy phenyl carbonate = 70 29.4
Toluene = 985 413.7
194
ANNEXURE - XII
PRODUCT : Vildagliptin
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
(3)-1-(2-Chloroacytyl)pyrrolide-2-
= 42 17.64
carbonitrile
Amantadine Hydrochloride = 63 26.46
Nitric acid (70%) = 40 16.80
Potassium Iodide = 1 0.42
Sulfuric acid = 84 35.28
195
ANNEXURE - XII
PRODUCT : Palonosetron Hydrochloride

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
(S)-N-(1-Azabicyclo[2,2,2]oct-3-yl)-5,6,7,8-
= 107 8.03
tetrahydro-1-naphthalene carboxamide
Diemthylformamide = 60 4.5
Ethanol = 500 37.5
Hydrogen = 1 0.08
Hydrogen Chloride = 15 1.13
Toluene = 800 60
196
ANNEXURE - XII
PRODUCT : Salmeterol Xinafoate

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
1-Hydroxy-2-naphthoic acid = 17 2
4-Hydroxy-α'-aminomethyl metaxylene-α,α'-
= 17.5 2
diol
4-Phenylbutoxy chlorohexane = 25 3
Acetone = 200 24
Methanol = 50 6
Toluene = 500 60
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
1,3-Dicyclohexyl carbodiimide = 71 17.04
1H-Indole-2-carboxylic acid = 45 10.8
Acetone = 790 189.6
Aluminum Chloride = 20 4.8
Benzene = 10 2.4
Benzyl Alcohol = 44 10.56
Carbon = 2 0.48
Ethanol = 170 40.80
Hydrogen = 5 1.2
Hyflo = 3.5 0.84
Maleic Anhydride = 20 4.8
Methanol = 1120 268.8
p-Toluenesulfonic acid = 25 6
Rhodium on Carbon = 0.5 0.12
197
ANNEXURE - XII
PRODUCT : Ecabapide
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
2-Chloro-N-(2-(3,4-dimethoxy phenyl)ethyl)
= 24 5.8
acetamide
3-Amino-N-methyl benzamide = 15 3.6
Calcium Carbonate = 18 4.3
Diethyl Ether = 120 28.8
Ethanol = 30 7.2
Methanol = 80 19.2
Sodium Bisulfite (5%) = 110 26.4
Sodium Carbonate (10%) = 172.5 41.4
Sodium Iodide = 5 1.2
PRODUCT : Zafirlukast
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
5-Nitro-1H-indole = 27 4.86
Acetone = 400 72.00
Cyclopentyl chloroformate = 21 3.78
Dimethylsulfate = 23 4.14
Hydrogen = 1 0.18
Hyflo = 2 0.36
Methyl-4-(bromomethyl)-3-methoxy
= 44 7.92
bezoate
Ortho Toluene Sulfonamide = 21 3.78
Sodium Sulfate = 2 0.36
Toluene = 560 100.80
198
ANNEXURE - XII
PRODUCT : Darifenacin Hydrobromide

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
3(S)-(1-Carbamoyl-1,1-diphenyl methyl)
= 40
pyrrolidine 7.2
5-(2-Bromoethyl)-2,3-dihydro benzofuran = 34 6.1
Acetone = 260 46.8
Hydrogen Bromide = 10 1.8
Sodium Methoxide = 10 1.8

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
3-Chloropropanoyl Chloride = 102 204
Acetic acid = 32 64
Aluminium Chloride = 110 220
Benzene = 62 124
Carbon = 8 16
D-(-)Tartaric acid = 164 328
Dimethylamine (40%) = 100 200
Dimethylaminopyridine = 1 2
Hydrochloric acid (35%) = 260 520
Hydrogen Chloride = 8 16
Methanesulfonyl Chloride = 98 196
Methanol = 13 26
Naphthol = 92 184
Potassium Carbonate = 116 232
R-505 = 13 26
Sodium Borohydride = 16 32
Sodium Sulfate = 21 42
Toluene = 1085 2170
199
ANNEXURE - XII
PRODUCT : Ibudilast
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
2-Methylpyridine = 85 106.3
Carbon = 10 12.5
Chlorosulfonic acid = 114 142.5
Hydrobromic acid (48%) = 155 193.8
Hydroxylamine Hydrochloride = 57 71.3
Isobutyric Anhydride = 470 587.5
n-Hexane = 100 125.0
PRODUCT : Mesalamine
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
2-Hydroxy-5-Nitrobenzoic acid = 66 132
Carbon = 7 14
Hydrogen = 3 6
Hydrose = 17 34
Raney Nickel 66 132
200
ANNEXURE - XII
PRODUCT : Pregabalin
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
D,L-Pregabalin = 272 544.0
Methanol = 1150 2300.0
S-Pregabalin Mandalate = 240 480.0
PRODUCT : Sumatriptan Succinate

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
(4-Hydrazinyl phenyl) metane sulfonyl
= 52 52
chloride
4-Chloro-1-hydroxy butane sulfonic acid = 47 47
Acetone = 100 100
Dimethylamine = 16 16
Methanol = 705 705
Methylamine (40%) = 20 20
Sodium Methoxide = 3 3
Succinic acid = 17 17
Toluene = 1145 1145
201
ANNEXURE - XII
PRODUCT : Voriconazole
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
3-(6-Chloro-5-fluoropyrimidin-4-yl)-2-(2,4-
difluorophenyl)-1-(1H-1,2,4-triazol-1-yl) = 190 38.0
butan-2-ol
Acetone = 780 156.0
Hydrogen = 10 2.0
Methanol = 1150 230.0
Propanol = 880 176.0
R(-)-10-Camphorsulfonic Acid = 110 22.0
Raney Nickel = 66 13.2
Sodium Acetate = 48 9.6
PRODUCT : Gemifloxacin Mesylate

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
(Z)-tert-Butyl-3-{(tert-butoxy carbonyl
amino)methyl)-4-(methoxyimino) = 668 64.1
pyrrolidine-1-carboxylate
Carbon = 56 5.4
Ethanol = 3120 299.5
Gemic acid = 480 46.1
Methanesulfonic acid = 700 67.2
Methanol = 3480 334.1
202
ANNEXURE - XII
PRODUCT : Rasagiline Mesylate

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
Acetone = 360 43.2
Indane Hydrochloride = 40 4.8
Methane Sulfonic aicd = 22 2.6
Propargyl Chloride = 18 2.2
Toluene = 400 48.0
PRODUCT : Valsartan
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
(S)-Methyl-2-amino-3-methyl butanoate
= 35 70
Hydrochloride
2-Cyano-4'-Bromomethylbiphenyl = 57 114
Potassium Carbonate = 33 66
Sodium Azide = 16 32
Sodium Carbonate = 26 52
Toluene = 410 820
Tributyltin Chloride = 83 166
Valeryl Chloride = 23 46
203
ANNEXURE - XII
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
4-Hydroxy-2-oxo-2H-chromen-3-ylium = 46 115.0
Ammonia gas = 5 12.5
Carbon = 7 17.5
Chlorosulfonic acid = 35 87.5
Ethyl Acelate = 1445 3612.5
Hydroxylamine Hydrochloride = 25 62.5
Hyflow = 7 17.5
Toluene = 200 500.0
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
1-Methyl-3-phenylpiperazine = 60 60
2-Chloronicotinonitrile = 48 48
Butanol = 550 550
Carbon = 7 7
Hyflow = 7 7
Methanol = 150 150
n-Hexane = 100 100
Potassium Fluoride = 1.3 1
Potassium Hydroxide = 25 25
Sodium Hydroxide (50%) = 50 50
Sulfuric acid = 30 30
Toluene = 508 508
Vitride (40%) in Toluene = 140 140
204
ANNEXURE - XII
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
Acetone = 200 200
Carbon = 8 8
Hydrogen = 5 5
Hyflow = 10 10
Methanol = 400 400
Minocycline Hydrochloride = 35 35
Nitric acid = 5 5
Palladium Carbon = 12 12
Phosphorus Pentachloride = 120 120
sec -Butanol = 350 350
Sulfuric acid = 20 20
t -Butyl bromoacetate = 178 178
t -Butylamine = 135 135
Toluene = 800 800
205
ANNEXURE - XII
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
1-Bromo-2,4-difluorobenzenene = 205 41
4-Methylene piperdine Hydrochloride = 58 12
Acetic acid = 100 20
Dihydropyran = 128 25.6
Isopropyl Acetate = 200 40
Lithium Hydroxide = 21 4.2
Magnesium turnings = 25.5 5.1
Methanol = 235 47
Methansulfonic acid = 5 1
Methansulfonyl chloride = 64 12.8
Methyl tert-butyl ether = 550 110
Methyl-(R)-Lactate = 105 21
Morpholine = 90 18
n-Heptane = 100 20
n-Hexane = 135 27
p-Toluenesulfonic acid = 55 11
Sodium Chloride (10%) solution = 130 26
Sodium Methoxide = 74 14.8
Sodium Sulfate = 50 10
Sodium tert-butoxide = 80 16
Triazole = 57 11.4
Trimethyl sulfoxonium iodide = 180 36
206
ANNEXURE - XII

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
2-Chloroethanol = 33 110
Carbon = 10 33.3
Methanol = 500 1666.7
P -Chloro Benzophenone = 114 380
Piperazine = 40 133.3
Sodium Monochloro Acetate = 35 116.7
Toluene = 4800 16000

Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
1,4-Dibromobutane = 51 5.1
2,2,2-Trifloroethylamine = 17 1.7
4'-(Trifluoromethyl)biphenyl-2-carboxylic
= 28 2.8
acid
9H-Fluorene-9-carboxylic acid = 49 4.9
n-Butyllithium (20%) in Hexane = 206 20.6
Oxalyl Chloride = 36 3.6
Piperidin-4-amine = 13 1.3
207
ANNEXURE - XII
PRODUCT : Ospemifene
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
2-Bromoethanol = 223 22.3
3-Chloro-1-phenylpropan-1-one = 235 23.5
4-Hydroxybenzophenone = 272 27.2
Methanol = 2400 240.0
Titanium Tetrachloride = 765 76.5
Zinc Dust = 531 53.1
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
1-(2,2-Difluorobenzo[d][1,3] dioxol-5-yl)
= 86 8.6
cyclopropane carbonyl chloride
2-Amino-5-methylpyridine = 84 8.4
3-Boronobenzoic acid = 35 3.5
Hydrogen Peroxide (50%) = 83 8.3
Methanol = 750 75.0
Pd(dppf)Cl2 = 8 0.8
Pivaloyl Chloride = 95 9.5
208
ANNEXURE - XII
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
2-(5-Bromo-2-methylbenzyl)-5-(4-
= 357 59.50
fluorophenyl)thiophene
Ammonium Chloride = 38 6.33
Boran trifloride etharate = 90 15.00
Gluconolacotone = 193 32.17
Hydrogen = 4 0.67
Methanol = 850 141.67
N-Methylmorpholine = 983 163.83
Sodium Dihydrogen Phosphate = 10 1.67
Toluene = 1920 320.00
Triethylsilane = 50 8.33
Trimethylsilyl Chloride = 1037 172.83
209
ANNEXURE - XII
PRODUCT : (S)-2-(tert-Butoxycarbonylamino)-3-(4-
carbamoyl-2,6-dimethylphenyl)propanoic acid
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
(Z)-Methyl 2-(tert-Butoxycarbonyl amino)-3-
= 85 8.50
(4-carbamoyl-2,6-dimethylphenyl)acrylate
Hydrogen = 7 0.70
Lithium Hydroxide = 10 1.00
Rh(cod)(r r-dipamp)bf4 = 10 1.00
PRODUCT : Empagliflozin
Consumption of
Daily
Raw Material /
Batch of
Raw Material
Product
Kg Kg
(4-(5-Bromo-2-chlorobenzyl) phenoxy)(tert-
= 243 40.5
butyl) dimethyl silane
(R)-Tetrahydrofuran-3-yl 4-
= 104 17.3
methylbenzenesulfonate
3,4,5-tris(trimethylsilyloxy)-6-
((trimethylsilyloxy)methyl) tetrahydro- = 277 46.2
2Hpyran-2-one
Boran trifloride etharate = 98 16.3
Caesium Carbonate = 140 23.3
Methanol = 1220 203.3
Triethylsilane = 60 10.0
210
Effluent Treatment Plant – Zero Liquid Discharge
ANNEXURE - XIII
Solvents for Recovery /

PCB Auth. Party
(with moisture)
Condenser
LTDS / LCOD &
Domestic Effluent
inlet
Condensate
Steam Stripper
Condenser
Pre aeration
HTDS / HCOD tank
Effluent inlet
Collection cum Neutrali-
MEE System
Pre aeration tank

Equalization zation Holding
Tank Tank
Aeration Storage Dual
Concentrate Tank media
Condensate Tank
Filtrate filter
Scrubber
ATFD
Effluent inlet
Filtrate
Sludge recycle
Sludge Decanter
and dried sludge to
TSDF Sludge Decanter
ACF
Salts to TSDF
and dried sludge to
TSDF
Product water to
R.O. System
RO / Used to Cooling Tower Storage
Utilities
Tank
Rejects
Evaporation
Forced
Condensate to
Utilities Salts to TSDF
211
1
ANNEXURE - XIV
Schematic flow Sheet for EIA Procedure
Time schedule for obtaining the EC from MOEF
Category A Project
30 days on obtaining
Preparation of FORM I Application & Prefeasibility report information from industry
as per check list
Submission of application by proponent (Form 1, Pre-feasilibility report and Draft Terms of Reference)
Scrutiny 60 days
by EAC
Scoping
Scoping an communication of Terms of Reference for EIA Studies to the Proponent for EIA preparation
120 days minimum other than monsoon

Preparation of Draft EIA report
period of 120 days
Submission of Draft EIA / Summary EIA / Application for Public consultation
Public Consultancy
45 days
Conducting public hearing by SPCB / PCC or any other public Agency / authority engaged by regulatory authority
Submission of proceedings of the public hearing by the SPCB / PCC to EAC

30 days for preparation of Final REIA Maximum
Submission of final EIA by the proponent after improving EIA / EMP
Appraisal
60 days
Appraisal by EAC
45 days
Issuing clearance to project
Decision of
MoEF proponent
Decision Making
Specific Concerns
60 days
Reservation on the proposal conveyed to EAC
EAC views on reservations sent to MoEF

30 days
212
ANNEXURE - XIV
NO Yes
Decision
Rejection of MoEF
Approach of EIA Study – 4 months other than monsoon period after

obtaining TOR copy from MOEF
Project Features
EIA Team Valued Environment
(Pre-feasibility Report,
Components
Form1)
Identification of Likely Impacts

(Quantitative Significance Analysis
(Ref: Impact Matrix)
Environmental Baseline Monitoring

(To Establish quality of the
Environment)
Application of Impact Prediction Tools

Social Impact (Quantitative Significance Analysis)
Risk Assessment
Assessment
Mitigation Measures
Environmental Management Plan
Reporting
213
ANNEXURE - XV
Google Map Showing Proposed Project Maithri Drugs Pvt. Ltd
214
ANNEXURE - XVI
215
ANNEXURE - XVII
(Soil)
216
ANNEXURE - XVIII
217

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Pre-Feasibility Report

(Proposed Expansion of APIs & Its Intermediate

M/s. Maithri Drugs Pvt. Ltd.

S.No Description Page No

1.0 Executive Summary 5

1|P a g e KKB ENVIROCARE CONSULTANTS PVT LTD., HYDERABAD, TS

S.No Description Page No

4.8 Social Infrastructure 29

5.3 Land use Planning 30

2|P a g e KKB ENVIROCARE CONSULTANTS PVT LTD., HYDERABAD, TS

S.No Description Page No

3|P a g e KKB ENVIROCARE CONSULTANTS PVT LTD., HYDERABAD, TS

4|P a g e KKB ENVIROCARE CONSULTANTS PVT LTD., HYDERABAD, TS

1.0 Executive Summary

5|P a g e KKB ENVIROCARE CONSULTANTS PVT LTD., HYDERABAD, TS

Table 1: Salient features of the proposed project

S.No Parameter Description

6|P a g e KKB ENVIROCARE CONSULTANTS PVT LTD., HYDERABAD, TS

7|P a g e KKB ENVIROCARE CONSULTANTS PVT LTD., HYDERABAD, TS

2.1 Identification of the Proposed Project

The proposed expansion of APIs and its Intermediates manufacturing unit is

2.2 Project Proponent

MSN Group is one of the fastest growing manufacturers of Active Pharmaceutical

8|P a g e KKB ENVIROCARE CONSULTANTS PVT LTD., HYDERABAD, TS

2.3 Brief Description of Nature of the Project

The manufacturing process of API’s consists of chemical synthesis extending to

9|P a g e KKB ENVIROCARE CONSULTANTS PVT LTD., HYDERABAD, TS

2.5 Demand and Supply Gap

2.6 Imports vs. Indigenous production, Export Possibility, Domestic/Export

10 | P a g e KKB ENVIROCARE CONSULTANTS PVT LTD., HYDERABAD, TS

3.0 Project description

11 | P a g e KKB ENVIROCARE CONSULTANTS PVT LTD., HYDERABAD, TS

Figure 1. Location of the proposed project

12 | P a g e KKB ENVIROCARE CONSULTANTS PVT LTD., HYDERABAD, TS

3.3 Alternate sites

The proposed project is located in the notified industrial area.

3.4 Size or Magnitude of Operation

Table 3: Existing products with its capacity

Sl. Product name Capacity Capacity

13 | P a g e KKB ENVIROCARE CONSULTANTS PVT LTD., HYDERABAD, TS

Table 4: Proposed Products with its Capacity

Sl. Product name Capacity Capacity

14 | P a g e KKB ENVIROCARE CONSULTANTS PVT LTD., HYDERABAD, TS

3.5 Project Description

3.6 Raw Materials

15 | P a g e KKB ENVIROCARE CONSULTANTS PVT LTD., HYDERABAD, TS

3.7 Resources Optimization / Recycling and Reuse

3.8 Availability of Water and Energy

16 | P a g e KKB ENVIROCARE CONSULTANTS PVT LTD., HYDERABAD, TS

EFFLUENT DETAILS SOLID WASTE Emissions

19 | P a g e KKB ENVIROCARE CONSULTANTS PVT LTD., HYDERABAD, TS

EFFLUENT DETAILS SOLID WASTE Emissions

20 | P a g e KKB ENVIROCARE CONSULTANTS PVT LTD., HYDERABAD, TS

EFFLUENT DETAILS SOLID WASTE Emissions

21 | P a g e KKB ENVIROCARE CONSULTANTS PVT LTD., HYDERABAD, TS

EFFLUENT DETAILS SOLID WASTE Emissions

22 | P a g e KKB ENVIROCARE CONSULTANTS PVT LTD., HYDERABAD, TS

Table 6: Existing water requirement and Wastewater generation

23 | P a g e KKB ENVIROCARE CONSULTANTS PVT LTD., HYDERABAD, TS

Table 7: Water balance and Segregation

Fresh Recycled Generation / Total

4 Cooling 185 175 330 30