FORM-I
For
PROPOSED EXPANSION OF BULK DRUGS AND BULK DRUG
INTERMEDIATES & FORMULATIONS IN EXISTING
MANUFACTURING UNIT
of
M/s. SULESHVARI PHARMA
Plot No. 6012/1, GIDC, Ankleshwar – 393 002,
Dist. Bharuch, Gujarat, INDIA.
APPENDIX I
FORM 1
(I)
Sr.
No.
1.
2.
3.
Basic Information
Item
Details
M/s. Suleshvari Pharma
5(f)
Please refer Annexure-1.
4.
Name of the Project/s
S.No. in the Schedule
Proposed capacity / area / length /
tonnage to be handled/command
area/lease area/number of wells to be
drilled
New/Expansion/Modernization
5.
Existing capacity/area etc.
Existing Capacity: 22.5 MT/Month
6.
7.
Category of project i.e. ‘A’ or ‘B’
Does it attract the general condition?
If yes, please specify.
Does it attract the specific condition?
If yes, please specify.
Location
Plot/Survey/Khasra No.
Village
Tehsil
District
State
Nearest railway station/airport along
with distance in kms.
Nearest
Town,
city,
District
Headquarters along with distance in
kms.
Village Panchayats, Zilla Parishad,
Municipal corporation, Local body
(Complete postal addresses with
telephone nos. to be given)
Name of the applicant
Registered address
‘A’
Yes. Located
(Ankleshwar).
N.A.
8.
9.
10.
11.
12.
13.
14.
15.
Address for correspondence:
Name
Designation (Owner/Partner/CEO)
Address
Expansion
in
critically
polluted
area
Plot. No. 6012/1
GIDC, Ankleshwar
Ankleshwar - 393 002
Bharuch
Gujarat
Nearest Railway Station: Ankleshwar = 4 km
Nearest Airport
: Surat = 70 km
Nearest Town: Ankleshwar = 4 km
Nearest District Head Quarter: Bharuch = 15 km
Notified Area Authority, Ankleshwar
M/s. Suleshvari Pharma
Plot. No. 6012/1, GIDC, Ankleshwar - 393 002,
Dist: Bharuch, Gujarat, INDIA.
Mr. Ramesh Patel
Partner
M/s. Suleshvari Pharma
Plot. No. 6012/1, GIDC, Ankleshwar - 393 002,
Dist: Bharuch, Gujarat, INDIA.
Pin Code
E-Mail
Telephone No.
16.
17.
18.
19.
20.
21.
22.
23.
24.
Fax No.
Details of Alternative Sites examined,
if any location of these sites should be
shown on a topo sheet.
Interlinked Projects
Whether separate application of
interlinked
project
has
been
submitted?
If Yes, date of submission
If no., reason
Whether the proposal involves
approval/clearance under: If yes,
details of the same and their status to
be given.
(a)
The Forest (Conservation) Act,
1980?
(b) The Wildlife (Protection) Act,
1972?
(c)
The C.R.Z Notification, 1991?
Whether there is any Government
order/policy relevant/relating to the
site?
Forest land involved (hectares)
Whether there is any litigation
pending against the project and/or
land in which the project is propose to
be set up?
(a)
Name of the Court
(b) Case No.
(c)
Orders/directions of the Court,
if any and its relevance with the
proposed project.
393 002
[email protected]
Tel. : +91-2646-226676
Mob.: +91 9824014578
-No
No
Not applicable
Not applicable
Not applicable
Not applicable as proposed expansion activity is
going to occur within GIDC, Ankleshwar.
No
No
No
(II) Activity
1. Construction, operation or decommissioning of the Project involving actions, which will cause
physical changes in the locality (topography, land use, changes in water bodies, etc.)
Sr.
No.
Information/Checklist confirmation
1.1
Permanent or temporary change in land
No
use, land cover or topography including
increase in intensity of land use (with
respect to local land use plan)
1.2
Clearance of existing land, vegetation and
buildings?
Yes
Minor site clearance activities shall be carried
out to clear shrubs and weed.
1.3
1.4
Creation of new land uses?
Pre-construction investigations e.g. bore
houses, soil testing?
No
No
---
1.5
Construction works?
Yes
1.6
1.7
No
No
1.10
1.11
1.12
1.13
Demolition works?
Temporary sites used for construction
workers or housing of construction
workers?
Above ground buildings, structures or
Earthworks including linear structures, cut
and fill or excavations
Underground works including mining or
tunneling?
Reclamation works?
Dredging?
Offshore structures?
Production and manufacturing
Approved plan for construction is attached as
Annexure: 1.
---
1.14
Facilities for storage of goods or materials?
Yes
1.15
Facilities for treatment or disposal of solid
waste or liquid effluents?
Yes
1.16
Facilities for long term housing of
operational workers?
New road, rail or sea traffic during
construction or operation?
1.8
1.9
1.17
Yes
/No?
Details thereof (with approximate quantities /
rates, wherever possible) with source of
information data
Proposed expansion activity is within existing
estate at GIDC, Ankleshwar.
Yes
Approved plan for construction is attached as
Annexure: 1.
No
--
No
No
No
Yes
No
---List of Products and manufacturing process
attached as Annexure: 2.
Dedicated storage area for storage of Raw
Materials and finished products, solvents, etc.
shall be provided.
Effluent Treatment Plant will be installed to
treat effluent so as to achieve the GPCB norms.
Details of water consumption & effluent
generation with segregation of effluent
streams are attached as Annexure: 3.
Details of proposed Effluent Treatment Plant
are attached as Annexure: 4.
Details of Hazardous waste generation and
disposal is attached as Annexure: 5.
--
No
--
1.18
1.19
1.20
1.21
1.22
1.23
New road, rail, air waterborne or other
airports etc?
Closure or diversion of existing transport
routes or infrastructure leading to changes
in traffic movements?
New or diverted transmission lines or
pipelines?
Impoundment, damming, converting,
realignment or other changes to the
hydrology of watercourses or aquifers?
Stream crossings?
Abstraction or transfers or the water form
ground or surface waters?
No
--
No
--
No
--
No
--
No
Yes
1.24
Changes in water bodies or the land
surface affecting drainage or run-off?
No
-No ground water shall be used. The
requirement of raw water shall be met through
GIDC Water Supply.
--
1.25
Transport of personnel or materials for
construction, operation or
decommissioning?
Long-term dismantling or
decommissioning or restoration works?
Ongoing activity during decommissioning
which could have an impact on the
environment?
Influx of people to an area in either
temporarily or permanently?
Introduction of alien species?
Loss of native species of genetic diversity?
Any other actions?
No
--
No
There is no dismantling of any sort. Not
applicable.
No Impact on the Environment
1.26
1.27
1.28
1.29
1.30
1.31
No
No
No
No
No
2. Use of Natural resources for construction or operation of the Project (such as land, water, materials or
energy, especially any resources which are non-renewable or in short supply):
Sr.
No
2.1
2.2
2.3
2.4
2.5
2.6
Information/checklist confirmation
Land especially undeveloped or agriculture
land (ha)
Water (expected source & competing
users) unit: KLD
Yes/
No?
No
Yes
Minerals (MT)
Construction material -stone, aggregates,
sand / soil (expected source MT)
Forests and timber (source - MT)
No
Yes
Energy including electricity and fuels
source, competing users Unit: fuel (MT),
energy (MW)
Yes
No
Details there of (with approximate quantities/rates,
wherever possible) with source of information data
-Water requirement will meet through the GIDC Water
Supply. Detailed water balance is given as Annexure –
3.
Not applicable
Company shall use Sand, stone, Cement and
Structural Steel for Construction as required.
No wood shall be used as construction material or as
a fuel.
Power required from GEB is 100 KVA (Existing)
Power required from GEB will 250 KVA (Proposed)
1 D.G. Set – 150 KVA (Proposed) (For Emergency Only)
Fuel:
Natural Gas = 300 m3/Day(Existing)
Agro Waste/Briquettes = 5 MT/Day (Proposed)
HSD = 20 Liter/Hr (Proposed) (For Emergency Only)
2.7
Any other natural resources
appropriates standard units)
(use
No
--
3. Use, storage, transport, handling or production of substances or materials, which could be harmful to
human health or the environment or raise concerns about actual or perceived risks to human health.
Sr.
No.
Information / Checklist confirmation
Yes/
No?
3.1
Use of substances or materials, which are hazardous
(as per MSIHC rules) to human health or the
environment (flora, fauna, and water supplies)
Yes
3.2
Changes in occurrence of disease or affect disease
vectors (e.g. insect or water borne diseases)
Affect the welfare of people e.g. by changing living
conditions?
No
3.4
Vulnerable groups of people who could be affected
by the project e.g. hospital patients, children, the
elderly etc.,
No
3.5
Any other causes
No
3.3
Details
thereof
(with
approximate
quantities / rates wherever possible) with
source of information data
Please refer Annexure : 6.
Not applicable as site is located at GIDC,
Ankleshwar.
Not applicable as site is located at GIDC,
Ankleshwar.
No
Not applicable as site is located at GIDC,
Ankleshwar.
4. Production of solid wastes during construction or operation or decommissioning MT/month)
Sr.
No.
Information/Checklist confirmation
Yes/
No?
4.1
4.2
No
No
--
4.7
Spoil, overburden or mine wastes
Municipal waste (domestic and or
commercial wastes)
Hazardous wastes (as per Hazardous Waste
Management Rules)
Other industrial process wastes
Surplus product
Sewage sludge or other sludge from effluent
treatment
Construction or demolition wastes
Details thereof (with approximate
quantities / rates, wherever possible)
with source of information data
--
4.8
4.9
4.10
4.11
Redundant machinery or equipment
Contaminated soils or other materials
Agricultural wastes
Other solid wastes
4.3
4.4
4.5
4.6
Yes
Please refer Annexure: 5
Yes
No
Yes
Please refer Annexure: 5
-Please refer Annexure: 5
No
Construction waste shall be utilized for
leveling & land filling in the premises.
---Please refer Annexure: 5
No
No
No
Yes
5. Release of pollutants or any hazardous, toxic or noxious substances to air (Kg/hr)
Sr.
No.
Information/Checklist confirmation
Yes/
No?
5.1
Emissions from combustion of fossil fuels
From stationary or mobile sources
Emissions from production processes
Yes
5.3
Emissions from materials handling including
storage or transport
Yes
5.4
Emissions from construction
including plant and equipment
activities
No
5.5
Dust or odours from handling of materials
including construction materials, sewage
and waste
No
5.6
5.7
Emissions from incineration of waste
Emissions from burning of waste in open air
(e.g. slash materials, construction debris)
No
No
5.8
Emissions from any other sources
No
5.2
Yes
Details
thereof
(with
approximate
quantities/rates, wherever possible) with
source of information data
Details of flue & process gas emission are
attached as Annexure: 7
Reactors shall be connected to common
scrubber system.
Details of emission levels from process are
attached as Annexure: 7.
Details of Air Pollution Control measures are
attached as Annexure: 7
All liquid raw materials shall be procured in
bulk tankers and shall be transferred through
a closed circuit pipe lines by pumps.
Solid raw material shall be handled in closed
charging rooms with proper ventilation and
charged through close pipeline into reactors.
Utmost care will be taken during construction
activity and water sprinklers shall be utilized
whenever necessary.
All the waste shall be stored in designated
places and shall be transported to TSDF or
Incineration Site in their own approved closed
vehicles.
6. Generation of Noise and Vibration, and Emissions of Light and Heat:
Sr.
No.
Information/Checklist confirmation
Yes/
No?
6.1
From operation of equipment e.g. engines,
ventilation plant, crushers
Yes
Details there of (with approximate Quantities
/rates, wherever possible) With source of source
of information data
There are few activities due to which noise would
be generated. The equipments resulting in noise
generation are machinery of plant and Diesel
generator. Adequate noise control measures will
be provided whenever required.
Proper and timely oiling, lubrication and
preventive maintenance will be carried out for
the machineries & equipments to reduce noise
generation.
Use of PPE like ear plugs and ear muffs will be
made compulsory near the high noise generating
machines.
6.2
From industrial or similar processes
Yes
6.3
6.4
6.5
6.6
6.7
From construction or demolition
From blasting or piling
From construction or operational traffic
From lighting or cooling systems
From any other sources
No
No
No
No
Yes
Noise monitoring shall be done regularly in plant
area.
The D.G. Set will be installed in a closed room and
provided with acoustic enclosure.
The unit will carry out plantation in the proposed
greenbelt within the premises which will prevent
the noise pollution in surrounding area.
All machinery / equipment shall be well
maintained, shall have proper foundation with
anti vibrating pads wherever applicable and noise
levels will be within permissible limits.
Acoustic enclosures shall be provided for DG set.
----Acoustic enclosures shall be provided for DG set.
7. Risks of contamination of land or water from releases of pollutants into the ground or into sewers,
surface waters, groundwater, coastal waters or the sea:
Sr.
No
7.1
Information/Checklist confirmation
7.2
From discharge of sewage or other
effluents to water or the land (expected
mode and place of discharge)
By deposition of pollutants emitted to air
into the land or into water
From any other sources
Is there a risk of long term build up of
pollution in the environment from these
sources?
7.3
7.4
7.5
From handling, storage, use or spillage of
hazardous materials
Yes/
No?
Yes
No
No
No
Yes
Details thereof (with approximate quantities / rates,
wherever possible) with source of information data
All the raw material shall be stored separately in
designated storage area and safely. Bund walls shall be
provided around raw materials storage tanks for
containing any liquid spillage.
Other materials shall be stored in bags / drums on
pallets with concrete flooring and no spillage is likely to
occur. Please refer Annexure : 6.
--
Adequate EMS will be provided and the factory is
located in GIDC, Ankleshwar.
Not applicable
Full- fledged Environmental Management System (EMS)
will be installed. i.e. ETP, Air Pollution Control systems,
Hazardous Waste Handling and Management as per
norms, etc. which will eliminates the possibility of
building up of pollution.
8. Risks of accident during construction or operation of the Project, which could affect human health
or the environment:
Sr.
No
8.1
Information/Checklist confirmation
From explosions, spillages, fires etc from
Yes/
No?
Yes
Details
thereof
(with
approximate
quantities / rates, wherever possible) with
source of information data
The risk assessment will be carried out and
8.2
8.3
storage, handling, use or production of
hazardous substances
From any other causes
Could the project be affected by natural
disasters causing environmental damage
(e.g. floods, earthquakes, landslides,
cloudburst etc)?
No
No
all mitigative measures shall be taken to
avoid accidents.
Not applicable
--
9. Factors which should be considered (such as consequential development) which could lead to
environmental effects or the potential for cumulative impacts with other existing or planned activities in
the locality
Sr.
No.
9.1
9.2
9.3
9.4
Information/Checklist confirmation
Lead to development of supporting. laities,
ancillary development or development
stimulated by the project which could have
impact on the environment e.g.:
* Supporting infrastructure (roads, power
supply, waste or waste water treatment,
etc.)
•
housing development
•
extractive industries
•
supply industries
•
other
Lead to after-use of the site, which could
have an impact on the environment
Set a precedent for later developments
Have cumulative effects due to proximity
to Other existing or planned projects with
similar effects
Yes/
No?
Yes
No
No
No
Details thereof (with approximate quantities
/ rates, wherever possible) with source of
information data
Site is located in GIDC, Ankleshwar, having
the entire required infrastructure.
This industrial zone is having existing road
infrastructure, power supply are to be
utilized.
Local people will be employed and no housing
is required.
Please refer Annexure – 8.
-Not applicable
The ETP of the company shall be designed
such that the treated effluent conforms to
the statutory requirement.
(III) Environmental Sensitivity
Sr.
No
1
2
3
4
5
6
7
8
9
10
11
12
Information/Checklist confirmation
Name / Aerial distance (within 25 km). Proposed
Identity Project Location Boundary.
Areas protected under international conventions
No
Site is located in GIDC, Ankleshwar, Tal.
national or local legislation for their ecological,
Ankleshwar, Dist. Bharuch, Gujarat.
landscape, cultural or other related value
Areas which are important or sensitive for
No
Site is located in GIDC, Ankleshwar, Tal.
Ecological reasons - Wetlands, watercourses or
Ankleshwar, Dist. Bharuch, Gujarat.
other water bodies, coastal zone, biospheres,
mountains, forests
Areas used by protected, important or sensitive
No
Site is located in GIDC, Ankleshwar, Tal.
species of flora or fauna for breeding, nesting,
Ankleshwar, Dist. Bharuch, Gujarat.
foraging, resting, over wintering, migration
Inland, coastal, marine or underground waters
Yes
Arabian Sea: 25 Km
River Narmada: 7 Km
State, National boundaries
No
-Routes or facilities used by the public for to
No
Not applicable
recreation or other tourist, pilgrim areas.
Defense installations
Densely populated or built-up area
Areas occupied by sensitive man-made land
community facilities)
Areas containing important, high quality or
scarce resources (ground water resources,
surface
resources, forestry, agriculture,
fisheries, tourism, tourism, minerals)
Areas already subjected to pollution or
environmental damage. (those where existing
legal environmental standards are exceeded)
Are as susceptible to natural hazard which could
cause the project to present environmental
problems (earthquakes, subsidence ,landslides,
flooding erosion, or extreme or adverse climatic
conditions)
No
NIL
Yes
No
Bharuch city: 4 Lakh population
Yes
The project being in industrial area does
not affect agricultural land.
Yes
Site is located in GIDC, Ankleshwar, Tal.
Ankleshwar, Dist. Bharuch, Gujarat.
-
N.A.
I hereby given undertaking that the data and information given in the application and enclosures are true to
the best of my knowledge and belief and I am aware that if any part of the data and information submitted
is found to be false or misleading at any stage, the project will be rejected and clearance given, if any to the
project will be revoked at our risk and cost.
Date: July 10, 2017
Place: Ankleshwar
NOTE:
1. The projects involving clearance under Coastal Regulation Zone Notification, 1991 shall submit with the
application a C.R.Z. map duly demarcated by one of the authorized agencies, showing the project activities,
w.r.t. C.R.Z. (at the stage of TOR) and the reco
recommendations
mmendations of the State Coastal Zone Management
Authority (at the stage of EC). Simultaneous action shall also be taken to obtain the requisite clearance
under the provisions of the C.R.Z. Notification, 1991 for the activities to be located in the CRZ.
2. The projects to be located within 10 km of the National Parks, Sanctuaries, Biosphere Reserves, Migratory
Corridors of Wild Animals, the project proponent shall submit the map duly authenticated by Chief Wildlife
Warden showing these features vis-à-vis
vis th
the
e project location and the recommendations or comments of the
Chief Wildlife Warden thereon (at the stage of EC).
3. All correspondence with the Ministry of Environment & Forests including submission of application for
TOR/Environmental Clearance, subseque
subsequent
nt clarifications, as may be required from time to time,
participation in the EAC Meeting on behalf of the project proponent shall be made by the authorized
signatory only. The authorized signatory should also submit a document in support of his claim of being
b
an
authorized signatory for the specific project.
ANNEXURES LIST:
1
Plot layout
2
List of products with production capacity and raw materials
3
Brief manufacturing process, chemical reaction and mass balance
4
Details of water consumption and waste water generation
5
Details of effluent treatment plant
6
Details of hazardous/solid waste generation, management and disposal mode
7
Details hazardous chemical storage facility
8
Details of air pollution sources and control measures
9
Socio - Economic impacts
10
Proposed Terms Of References
11
GIDC Plot Allotment Letter & GIDC Water Supply Letter
12
Membership Certificate of CETP, ETL-Ankleshwar for disposal of treated effluent
13
Membership Certificate of TSDF & Common Incinerator, BEIL-Ankleshwar
ANNEXURE-1
PLOT LAYOUT
ANNEXURE-2
LIST OF PRODUCTS WITH PRODUCTION CAPACITY
Sr.
No.
Products
(A)
1
2
3
4
5
6
7
Bulk drugs/Bulk Drugs Intermediates
Iso Amyl Acetate
Iso Amyl Propionate
Iso Amyl Butyrate
Phenyl Ethyl Acetate
Phenyl Ethyl Propionate
Methyl -3- Amino Crotonate
Phthalimido Amlodipine
8
Diaminomethyleneamino (1-amino-1iminomethylene) thiomethyl thiozole
dihydrochloride [ITU]-50
Production Capacity
(MT/Month)
Existing
Additional
Total
1
1
1
1
1
1
1
Or
-----4
4
1
1
1
1
1
5
5
&
9
41
50
N-Sulfomyl-3-chloropropionamide
hydrochloride[IF]-50
10
Famotidine
11
Poly Allaylamine Hydrochloride
12
Sevelamer Hydrochloride
13
Sevelamer Carbonate
14
Fomepizole
15
Colsevelam hydrochloride
16
Glimepiride
17
Furosemide
18
Betahistine Dihydrochloride
19
Adapalene
9
Or
4
Or
9
Or
9
Or
9
Or
0.6
Or
7.5
Or
2.9
Or
9
Or
3.2
Or
1.5
Or
123-92-2
105-68-0
106-27-4
103-45-7
122-70-3
14205-39-1
88150-62-3
&
Or
9
CAS No.
41
6
191
106649-95-0
50
&
10
&
200
&
76824-35-6
71550-12-4
152751-57-0
845273-93-0
7554-65-6
182815-44-7
93479-97-1
54-31-9
5579-84-0
20
20
106685-40-9
20
Telmisartan
21
Tapentadol Hydrochloride
22 Colistimethate Sodium
Proposed
23 Rusvastatin Calcium
24 1-3 dichloro Acetone
25 Gunylthiourea
26 Rabeprazole Sodium
27 Carvediol
28 Celecoxib
29 Clopidogrel Bisulfate
30 Atoravastatin Calcium
31 Etoricoxib
32 Valsartan
33 Tranexamic Acid
34 Folic Acid
35 Zolpidic Acid
36 Pregabaline
Total (A)
Distillation(B)
(B)
37
38
OR
39
REPACKING
Benzophenone (Repacking)
Para
Cresyl
Phenyl
(Repacking)
Poly
Allaylamine
(Repacking)
6.5
Or
8
Or
3.5
144701-48-4
9
0
147098-20-2
534-07-6
2114-02-5
117976-90-6
72956-09-3
169590-42-5
120202-66-6
134523-03-8
202409-33-4
137862-53-4
1197-18-8
59-30-3
189005-44-5
148553-50-8
Acetate
3.0
0.5
Hydrochloride
13.5
175591-09-0
8068-28-8
336
25
345
25
100
113.5
100
461
113.5
483.5
OR
40
OR
41
42
Allaylamine (Repacking)
Allaylamine
Hydrochloride
(Repacking)
Micronization of Bulk Drugs/APIs
(Famotidine,
Amlodipine,
Glibenclamide,
Sevelamer
HCl,
Glimepride, Adapalene, ITU, IF,
Colsevelam
HCl,
Furosemide,
Telmisartan,
Betahistine
Dihydrochloride, Tapentadol HCl…etc)
Total (C)
Total (A+B+C)
13.5
13.5
-
13.5
22.5
LIST OF RAW MATERIALS AND CONSUMPTION:
Sr. No. Raw Material
1
Iso Amyl Acetate
Amyl alcohol
Catalyst
Toluene
Acetic acid
2
3
4
5
6
7
Quantity
(MT/MT)
Iso Amyl Propionate
Amyl alcohol
Catalyst
Toluene
Propionic acid
Iso Amyl Butyrate
Amyl alcohol
Catalyst
Toluene
Butyric acid
Phenyl Ethyl Acetate
Toluene
Acetic Acid
Phenyl Ethyl Alcohol
PTSA
Phenyl Ethyl Propionate
Toluene
Propionic Acid
Phenyl Ethyl Alcohol
PTSA
Methyl-3-Amino Crotonate
Methyl Aceto Acetate
Liq. Ammonia
Methanol
Phthalimido Amlodipine
Xylene
Phthalic Anhydride
Mono Ehanol Amine
Benzene
Sodium hydride
E4CAA
Acetic Acid
Methanol
Ortho Chloro Benzaldehyde : 129 Kg.
Morpholine
0.70
0.05
0.60
0.55
0.70
0.05
0.60
0.55
0.60
0.05
0.60
0.60
1.00
0.65
1.25
0.06
1.00
0.75
1.15
0.06
5.62
4.50
1.50
7.50
1.50
0.625
8.25
0.415
0.81
1.73
2.925
0.645
0.08
8
9
10
11
12
13
14
Methyl-3-Amino Crotonate : 294 Kg.
Mono Ethanol Amine
Diaminomethyleneamino
(1-amino-1iminomethylene)
thiomethyl
thiozole
dihydrochloride [ITU]
1,3 DCA
Guanyl Thiourea
Acetone
Catalyst
Thiourea
Acetic Acid
N-Sulfomyl-3-chloropropionamide
hydrochloride [IF]
Acrylonitrile
Hydrogen Peroxide
HCl (Gas)
Sulfamide
Acetone
Famotidine
ITU
IF
Methanol
NaOH
Water
Acetic Acid
Sevelamer Hydrochloride
Allylamine
2,2-Dimethyl-2,2-azopropane dihydrochloride
HCl
Epichlorhydrin
NaOH Flakes
Sevelamer Carbonate
SevelamerHCl
Caustic soda flakes
Carbon dioxide
Poly Allaylamine Hydrochloride
Allylamine
2,2-Dimethyl-2,2-azopropane dihydrochloride
HCl
Fomepizole
Propanaldehyde
Ethanol
Hexane
Phosphorus oxychloride
Hydrazine Hydrate
1.47
0.625
0.435
0.413
3.100
0.004
0.261
0.261
1.303
0.008
1.495
0.500
0.400
1.150
0.965
5.710
0.690
20.50
0.200
0.75
0.03
1.25
0.11
0.37
1.111
0.333
0.278
0.333
0.117
0.600
1.31
0.015
0.015
3.45
1.10
15
16
17
18
19
Potassium Carbonate
Carbon
Di isopropyl Ether
N,N-Dimethyl Formamide
Dichloro Methane
Colsevelam hydrochloride
Monoallylamine
2,2-dimethyl-2,2-azopropane dihydrochloride
Concentrated Hydrochloric acid
Methanol
Polyallylamine
Epichlorohydrin
n-Decylchloride
Trimethylammoniumhexylchloride
Sodium hydroxide
Glimepiride
3 Ethyl methyl Pyrroline
2 Phenyl ethyl isocyanate
Toluene
Chloro Sulfonic Acid
Ammonia Solution
EDC
Furosemide
Furfuryl Amine
Lasamide
Caustic Flake
IPA
Carbon
Acetic Acid
Betahistine Dihydrochloride
2- vinyl pyridine
Methylamine hydrochloride
Chloroform
Sodium hydroxide
Acetic Acid
IPA
IPA HCl(20%)
Adapalene
Adamentanol
Para Bromo Phenol
THF
Mg Turning
MDC
6-Bromo-2-methyl naphthoate
HCl
0.75
0.15
0.02
0.01
0.03
0.60
0.01
1.15
0.31
0.90
0.01
0.02
0.02
0.45
0.40
0.40
0.15
1.00
3.10
0.30
0.450
0.850
0.234
0.240
0.080
0.220
0.63
0.80
0.23
0.45
0.06
0.01
1.38
0.48
0.30
0.025
0.06
0.04
0.72
1.32
20
21
22
23
Telmisartan
4-Amino 3- Methylbenzoic acid
Conc. Sulphuric Acid
Liq. Ammonia
Methanol
MDC
TEA
Butryl Chloride
Sodium Bicarbonate
Sodium Sulphate
Hexane
Fuming Nitric Acid
Tapentadol Hydrochloride
3-methoxy propiophenone
IPA
Dimethyl Amine HCL
Paraformadehyde
Sodium Hydroxide
MDC
L (-) Dibenzoyl tartaric acid
THF
Mg Turning
Ethyl Bromide
Acetic Acid
Ammonium Solution
Ethyl Acetate
Trifluroacetic anhydride
Palladium
Acetone
HBr
IPA HCl
Colistimethate Sodium
Colistin Sulphate
Sodium Bicarbonate
Sodium Carbonate
Formaldehyde
Sodium Bisulfite
Acetic Acid
Solvent
Acetone
Methanol
Rusvastatin Calcium
4-Fluoro Benzaldehyde
1.484
1.423
2.968
0.06
0.03
0.01
1.287
0.153
0.387
0.02
4.050
1.412
0.350
1.059
0.588
0.376
0.350
1.412
0.080
0.171
0.588
0.118
0.506
0.230
0.882
0.070
0.260
1.765
0.882
1.33
0.67
0.33
1.33
3.06
0.16
0.80
2.00
3.00
0.52
24
25
26
4-Methyl-3-oxo-Pentatonic Acid Ethyl Ester
Potassium Hydroxide
Methyl Iodide
Methanol
5-Methyl Iso Thio Urea
2,3-Dichloro-5,6-Dicyano Benzoquinone
HMPA
MDC
Meta Chloro Peroxy Benzoic Acid
Methyl Amine
Ethanol
Methane Sulfonyl Chloride
Sodium Hydride (60%)
Di Methoxy Ethane
Hydrogen
DIBAL-H
Toluene
Methyl(3R)-3-(tert butyl dimethyl silyloxy)-5oxo-6-triphenyl phosphoranylidene hexanoate
Triethyl Amine
N,N-Dimethyl Formamide
Hydrogen Fluoride
THF
Ethyl Acetate
Diethyl Methoxy Borane
Sodium Borohydride
Calcium Chloride
1-3 dichloro Acetone
Epichlorohydrin
HCl (30%)
Sulfuric Acid (98%)
Sodium Dichromate
Gunylthiourea
Phosphorus Penta Sulphide
KOH
Dicyanadiamide
Sodium Hydro Sulphite
Rabeprazole Sodium
2,3-Lutidine
H2O2 (50%)
0.66
0.24
0.60
5.50
0.35
0.85
1.00
8.00
0.11
0.10
2.50
0.35
0.01
3.00
0.01
0.01
8.00
1.45
0.15
3.00
0.05
7.50
10.50
0.20
0.01
0.13
1.302
3.125
1.862
1.562
0.827
1.000
0.909
0.181
0.460
0.330
27
28
29
Nitric Acid
Acetic Acid
3-Methoxy 1-Propanol
NaOH
Toluene
DMSO
Acetic Anhydride
HCl
Thionyl Chloride
MDC
Sodium Sulphate
2-Mercaptobenzimidazole
Ammonium Hydroxide
Sodium Hypochlorite (8%)
Acetone
Sodium Hydro Sulphate
MMA
IPA
Activated Carbon
Carvediol
4-Hydroxy Carbazole
Epichlorohydrin
Hydrose
Methanol
Ethyl Acetate
Carbon
Hyflo
Monoethylene Glycol Dimethyl Ether
2-(2-Methoxy Phenoxy) Ethyl Amine
Acetone
Potassium Carbonate
Oxalic Acid
IPA
Sodium Sulphate
Ortho Phosphoric Acid
Celecoxib
4 SPH
Dione Deri
Toluene
Carbon
Clopidogrel Bisulfate
amino(2-chlorophenyl)acetic acid
Methanol
Potassium salt
0.380
0.060
0.430
0.155
0.012
0.010
0.390
0.200
0.530
0.370
0.100
0.530
0.125
3.270
0.100
0.120
0.100
0.150
0.100
0.447
0.790
0.116
0.067
0.029
0.022
0.005
2.330
0.956
0.101
0.372
0.532
0.052
0.207
0.442
0.70
0.65
2.80
0.01
1.25
0.20
0.7
30
MDC
Liq. ammonia
Thiophene-2-Ethanol
p-toluene sulphonyl chloride
Toluene
Sodium hydroxide
Acetonitrile
Dipotassium phosphate
Ethyl acetate
HCL
P-Formaldehyde
MDC
Liq. Ammonia
Acetone
Tartaric acid
MDC
Sodium carbonate
Acetone
Activated carbon
Sulfuric acid
Atoravastatin Calcium
Ethyl-4-Cyano-3-hydroxy butanaote
THF
Diisopropyl amine
N-Butyl Lithium
Tert-Butyl acetate
HCl
Ethyl Acetate
NaCl
Methanol
DEMB (50 % Soln)
Sodium Borohydride
Acetic Acid
Dimethoxy Propane
Methane Sulphonic Acid
Sodium Bicarbonate
n-Hexane
Raney Nickel
Pivalic Acid
0.50
0.62
0.5
1.05
0.16
1.25
0.32
0.87
0.28
0.85
0.53
1.02
0.60
1.10
0.82
0.67
0.70
0.24
0.15
0.31
1.00
0.85
1.22
0.6
1.68
0.76
1.5
1.20
1.02
0.70
0.44
0.98
1.81
0.03
2.00
0.023
1.00
0.240
31
32
33
Toluene
Activated Carbon
Methyl Tert Butyl
Etoricoxib
Acetic Acid
Acetone
Ammonia Solution
CPT-Phosphate
D M Water
Hydroxylamine Hydrochloride
Hyflow
Isopropyl Alcohol
Ketosulfone
Methanol
Potassium Tertrabutoxide (KTB)
Sodium Acetate
Sodium Hydroxide
Toluene
THF
Trifluro Acetic Acid
Activated Carbon
Hexane
Valsartan
L-Valine
Methanol
Thionyl Chloride
Toluene
DCM
NaOH
NaCL
4-Bromo Methyl 2-Cyano biphenyl
Acetonitrile
Potassium Carbonate
Oxalic Acid
o-Xylene
Valeoryl Chloride
Sodium Bicarbonate
HCl
Tributyl Tin Chloride
Calcium Hydroxide
Ethyl Acetate
Diisopropyl ether
TBAB
Tranexamic Acid
0.45
0.100
0.410
1.520
2.80
5.80
1.520
26.00
0.115
0.177
10.00
0.574
10.00
0.664
0.297
2.153
55.000
23.00
0.465
0.022
0.250
1.44
0.23
6.90
0.38
2.41
0.65
0.29
2.17
1.00
1.49
1.00
1.16
1.24
0.28
0.65
5.55
0.42
0.35
7.17
0.14
34
35
36
4-aminomethyl benzoic
Acid
HCl
Ruthenium
Sodium hydroxide
Methanol
Folic Acid
PABGA
TAPS
TCA
SMBS
NaHCO3
HCl 30%
NaOH
Acetic Acid
Zolpidic Acid
Toluene
Methyl Phenacyl bromide
2- Amino-5-methyl pyridine
Triethyl amine
Oxalyl chloride
Methylene Dichloride
Potassium hydroxide
Acetic acid
Hydrazine hydrate
Methanol
Pregabaline
Sodium Hydroxide
4-CMH
Liquid Bromine
Activated carbon
Hyflo
Hydrochloric acid
IPA
1.060
0.440
0.300
0.252
2.000
1.00
0.90
0.64
0.36
1.20
6.00
0.22
0.32
0.128
1.000
0.611
0.531
0.700
1.000
1.340
1.651
0.431
1.000
1.90
1.37
1.23
0.07
0.02
2.46
7.06
ANNEXURE-3
BRIEF MANUFACTRING PROCESS, CHEMICAL REACTION AND MASS BALANCE
Existing:
7. Diaminomethyleneamino(1-amino-1-iminomethylene) thiomethyl thiozole dihydrochloride [ITU]
Manufacturing Process:
Charge acetone into the reaction vessel. Chill acetone up to 10°C. Add slowly 1,3-Dichloro acetone within 1
hour maintain temp. 10 °C. Add KI (Lot-1) at 10°C and stir the reaction mass for 15 minutes. Add Guanyl
thiourea by maintaining temp. 12 °C to 15 °C. Add KI (Lot-2) at 15 °C to 20 °C and maintain for 3 hours. Add
acetic acid (glacial) at 20°C to 25°C temp. Heat the reaction mass to 40 °C temp. Now add thiourea and
acetone under stirring at 40 °C temp. Raise the temp. of the reaction mass to 55 °C to 60 °C. Reflux the
reaction mass at 55 °C to 60°C temp. for 3 hours. Cool the reaction mass to 30 °C temp. Further cool to 20
°C temp. Centrifuge the material and wash the wet cake with acetone. Unload the wet cake from the
centrifuge. Dry the wet cake in dryer at 95 °C to 100 °C temperature for 9 to 10 hours. Unload the dried
material and weight and packed it.
Chemical Reaction:
q
Mass Balance:
Sr.
No.
1
2
3
4
5
6
Total
Input
Quantity (Kg)
Output
Quantity (Kg)
1,3 DCA
Guanyl Thiourea
Acetone
Catalyst
Thiourea
Acetic Acid
0.435
0.413
3.100
0.004
0.261
0.261
4.474
Product
Evaporation Loss
Acetone Recover
Dist. Residue
1.000
0.400
3.000
0.074
Total
4.474
8. N-Sulfomyl-3-chloropropionamide hydrochloride [IF]
Manufacturing Process:
Charge Acrylonitrile into the reaction vessel. Add hydrogen peroxide (50 %) under stirring. Chill the reaction
mass to 15°C to 20°C. Purge HCl gas at 15°C to 20°C for 38 to 40 hours at the feeding rate of 0.8-1.0
Kg/hour. After completion of gas passing, degas the reaction mass. Now Add sulfamide under stirring at RT.
Cool the reaction mass to 18°C to 22°C temp. Further chill the reaction mass to 0°C to 10°C temp. Purge HCl
gas at 0°C to 10°C for 8 hours at the feeding rate of 0.8-1.0 Kg/hour. Raise the temp. of the reaction mass to
15°C to 20°C within 2 hours with continue HCl gas passing. Raise the temp. of the reaction mass to 50°C to
55°C within 2 to 3 hours with continue HCl gas passing. Maintain reaction mass at 50°C to 55°C for 5 hours
with continue HCl gas passing. Degas the reaction mass for 5 hours at 50°C to 55°C temp. Cool the reaction
mass to 28°C to 32°C temp. Further cool the reaction mass to 18°C to 22°C. Centrifuge the material and
wash the wet cake with chilled acetone. Unload the wet cake and dry the wet cake in dryer at 65°C to 70°C
temp. for 5 to 6 hours. Unload the dried material and record the weight and packed.
Chemical Reaction:
O
H2C
CH2CN
+
H2N
NH2
O
S
NH2
Cl CH2
CH2
C
N
(1)
(2)
(1) Acrylonitrile
(2) Sulfamide
(3) N-sulfomyl-3-chloropropionamidehydrochloride
(3)
SO 2NH2
Mass Balance:
Sr.
No.
1
2
3
4
5
6
Total
Input
Acrylonitrile
Hydrogen Peroxide
HCl (Gas)
Sulfamide
Acetone
Quantity (Kg)
1.303
0.008
1.495
0.500
0.400
3.706
Output
Product
Evaporation Loss
Acetone Recover
CAN Recover
Dist. Residue
Dil. HCl
Total
Quantity (Kg)
1.000
0.556
0.350
1.2907
0.050
0.46
3.706
10. Famotidine
Manufacturing Process:
STAGE-1: [FAMOTIDINE CRUDE]: Charge Methanol into the reaction vessel. Add caustic soda flakes and
reflux the reaction mass under stirring. Cool to 30°C and then chill to 20°C to 22°C temp. Now add ITU
(Diaminomethyleneamino(1-amino-1-iminomethylene) thiomethyl thiozole dihydrochloride) and IF (NSulfomyl-3-chloropropionamide hydrochloride) at 20°C to 22°C temp. Regulate the temperature to 25°C
and maintain for 2 hours under stirring. Chill the reaction mass to 0°C to 5°C 22.temp. Centrifuge the slurry.
Unload the wet material from the centrifuge. Charge water into the reaction vessel and add wet cake under
stirring. Stir for 30 minutes. Centrifuge the material and wash the wet cake with water and then wash with
methanol. Load the wet cake in dryer. Dry the wet cake at 80°C to 85°C temperature for 7 to 8 hours.
Unload the dried material and weight it.
STAGE-2: [FAMOTIDINE PURE]: Charge Water & caustic soda into the reaction vessel. Add Famotidine
Crude (Stage-1) under stirring. Heat the reaction mass to 70°C to 75°C temperature. Check the clarity of the
reaction mass. It should be clear. Now prepare the slurry of Activated carbon in water. Add activated
carbon slurry into the reaction mass at 70°C to 75°C temp. And maint. for 15 minutes. Filter the reaction
mass through pressure filter and transfer filtrate online to another reaction vessel maintaining temperature
30°C to 40°C. Add Acetic Acid & follow out the material Now chill the filtrate to 0°C to 5°C temp. and
maintain for 30 minutes. Centrifuge the slurry and wash the wet cake with water. Unload the wet cake and
weight it. Dry the wet cake in dryer at 75°C temperature for 5 to 6 hours. Unload the dried material and
weight it and packed it as Famotidine Pure.
Chemical Reaction:
NH
CH 2 S
NH2
C
N
NH 2
H 2N
+
2 HCl
C l CH 2
CH 2
C
N
C
SO 2 NH 2
NaOH
N
H 2N
S
(1)
(2)
NH 2
CH 2 S
CH 2
N
C
C
N
H 2N
H 2N
CH 2
SO 2 NH 2
N
S
(3)
(1) Diaminomethyleneamino(1-amino-1-iminomethylene)thiomethyl thiozole dihydrochloride
(2) N-Sulfamyl-3-chloropropionamidine hydrochloride
(8) Famotidine
Mass Balance:
Sr.
No.
1
2
3
4
5
6
Total
Input
ITU
IF
Methanol
NaOH
Water
Acetic Acid
Quantity (Kg)
1.150
0.965
5.710
0.690
5.00
0.200
13.715
Output
Product
Methanol Recover
Methanol Loss
Effluent
Evaporation Loss
Dist. Residue
Total
Quantity (Kg)
1.000
5.500
0.200
6.905
0.010
0.200
13.715
11. Sevelamer HCl
Manufacturing Process:
Stage-1 Preparation of Polyallylamine Hydrochloride
Into clean reactor charge 250 Kg Hydrochloric acid at room temperature. Add 150 Kg allylamine in 2 hrs at 5
to 10 °C. Raise the temperature 80 °C and add a solution of 2,2-dimethyl-2,2-azopropane dihydrochloride
(6.0 Kg in 44 Kg water) at 45 to 50 °C. Stir the mass 30 hrs at 45 to 50 °C. Monitor the reaction performance
by analytical methods. After completion of reaction, cool the mass to 25 to 30 °C Stir for 1 hr at 25 to 30 °C.
Expected weight is 450 Kg.
Stage-2 Preparation of Sevelamer
Add 150 Kg Sodium hydroxide solution (75 Kg in 75 Kg water) into 450 Kg Polyallylamine at room
temperature and stir for 30 minutes. add 22.0 Kg of epichlorohydrin into above solution at room
temperature and stir for 20 minutes. Heat the mass at 25 to 50 °C in 10 to 20 minutes. Cool to 30 °C and
stir for 30 minutes at 25 to 30 °C. Filter the slurry and wash the material and finally with 3 X 1500 Kg
Water. Collect the main and washing Mother Liquor together. Unload and dry the material at 45 to 50 °C in
vacuum tray drier (VTD) till to reach the required moisture content of the product. Expected weight is 200
Kg.
Chemical Reaction:
Stage –I (Preparation of Polyallylamine Hydrochloride):
H2C
allylamine
NH2
+
HCl
Hydrochloric acid
Polymerisation
25 to 80ºC
Water
.
.
.HCl
NH2
n
Polyallylamine Hydrochloride
Stage – 2 (Preparation of Sevelamer):
.
.HCl
.
O
NH2
Cl
n
+
Na OH
+
Polyallylamine Hydrochloride
Epichlorohydrin
Cross Linking
Sodium Hydroxide
Water
25 to 50ºC
CH3
H3C
H2N.nHCl
HN .nHCl
a
OH
H2N .nHCl
HN .nHCl
H3C
b
Sevelamer
a, b = number of primary amine groups
c = number of cross linking groups
n = fraction of protonated amines
m = large number to indicate extended polymer network
c
m
CH3
Mass Balance:
Sr. Input
No.
1
Allylamine
2
2,2-Dimethyl-2,2azopropane
dihydrochloride
3
HCl
4
Water
5
Epichlorhydrin
6
NaOH Flakes
Total
Quantity (Kg)
Output
Quantity (Kg)
150
6
Product
Effluent
200
2250
250
2119
22
75
2622
Evaporation Loss
172
Total
2622
12. Sevelamer Carbonate
Manufacturing Process:
• Charge Purified Water and Sevelamer Hydrochloride.
• Charge Caustic Soda flakes.
• Purge Carbon Dioxide gas.
• Filter the mass and wash with Water.
• Dry wet material to give Sevelamer Carbonate.
Chemical Reaction:
Mass Balance:
Sr. Input
No.
1
SevelamerHCl
2
Caustic soda flakes
3
Carbon dioxide
4
Water
Total
Quantity
(Kg)
1.111
0.333
0.278
37.778
39.500
Output
Product
Effluent
Quantity
(Kg)
1.000
35.556
Evaporation Loss
2.944
Total
39.500
13. Poly Allaylamine Hydrochloride
Manufacturing Process:
Into clean reactor charge 250 Kg Concentrated hydrochloric acid at room temperature. Add 150 Kg
allylamine in 2 hrs at 5 to 10 °C. Raise the temperature 80 °C and add a solution of 2,2-dimethyl-2,2azopropane dihydrochloride (6.0 Kg in 44 Kg water) at 45 to 50 °C. Stir the mass 30 hrs at 45 to 50 °C.
Monitor the reaction performance by analytical methods. After completion of reaction, cool the mass to 25
to 30 °C Stir for 1 hr at 25 to 30 °C. Expected weight is 450 Kg.
Chemical Reaction:
H2C
NH2
allylamine
+
HCl
Hydrochloric acid
Polymerisation
25 to 80ºC
Water
.
.HCl
.
NH2
n
Polyallylamine Hydrochloride
Mass Balance:
Sr. Input
No.
1
Allylamine
2
2,2-Dimethyl-2,2azopropane
dihydrochloride
3
HCl
4
Water
Total
Quantity (Kg)
Output
Quantity (Kg)
150
6
Product
450
Total
450
250
44
450
14. Fomepizole
Manufacturing Process
Stage-1 Preparation of 1, 1-Diethoxy Propane
Into reactor, charge 395 Kg Ethanol and 131 Kg Propanaldehyde at room temperature. Heat the mass to
90ºC and reflux for 15 hrs.
Cool the mass to room temperature.
Add 390 Kg Hexane and stir for 30
minutes at room temperature. Separate the layers. Distill out the Hexane completely at 80ºC.
Expected weight is 300 Kg
Stage-2 Preparation of Fomepizole
Into the reactor charge 233 Kg N,N-Dimethyl formamide and 300 Kg 1,1- Diethoxy Propane at room
temperature. Add 535 Kg Phosphorus oxychloride solution
(345 Kg in 190 Kg N,N-Dimethyl formamide) into the mass in 14 hrs at 90ºC. Cool to 50ºC and stir for 12
hrs. Monitor the reaction performance by analytical methods. After completion of reaction cool the mass
to room temperature. Into the mass add 2000 Kg Water and 2680 Kg Dichloro methane and stir for 30
minutes. Separate the layers and distill out Dichloro methane completely at below 50ºC.
Into the above mass, add 2010 Kg Dichloro methane and 110 Kg Hydrazine hydrate at room temperature.
Heat the mass to 100ºC reflux for 15 hrs at the reflux temperature. Monitor the reaction performance by
analytical methods. After completion of reaction cool the mass to room temperature. Add 2000 Kg Water
into the mass and adjust the pH to 7.0 using Potassium carbonate solution (75 Kg in 750 Kg Water).
Separate the layers and wash the dichloro methane layer with 1000 Kg Water.
Distill out Dichloro
methane completely under vacuum at below 40ºC.
Add 425 Kg Di isopropyl ether and stir for 30 minutes at room temperature. Add 15 Kg Carbon and stir for
30 to 40 minutes at room temperature. Filter and wash with
73 Kg Di isopropyl ether. Distill out Di isopropyl ether completely under vacuum at below 50ºC.
the vacuum and unload the liquid Fomepizole.
Release
Chemical Reaction
Stage – 1 (Preparation of 1,1-Diethoxy Propane)
H3C
O
O
CH3
O
H3C
H3C
OH
Ethanol
H
+
H3C
Hexane / 90ºC
Propanaldehyde
1,1-Diethoxy Propane
Stage-2 (Preparation of Fomepizole)
H3C
O
O
CH3
Cl
Cl
P
H3C
1,1-Diethoxy Propane
+
Cl
O
+
Phosphorous
Oxychloride
H2N
NH2. H O
2
Hydrazine Hydrate
N,N-Dimethyl Formamide (DMF)
Dichloro Methane (MDC)
Water
50ºC/ 90ºC
100ºC
H
N
N
H3C
Fomepizole
Mass Balance:
Sr. Input
No.
Step-1
1
Propanaldehyde
2
Ethanol
3
Hexane
4
5
6
Total
Quantity
(Kg)
Sr. Input
No.
Step-2
1
Step-I
2
Phosphorus
oxychloride
3
Hydrazine Hydrate
4
Potassium Carbonate
5
Carbon
6
Di isopropyl Ether
7
N,N-Dimethyl
Formamide
8
Dichloro Methane
9
Water
10
Quantity
(Kg)
Output
Quantity
(Kg)
300
Product
100
345
Dichloro methane
4670
110
75
15
498
Dichloro methane loss
Dimethyl formamide
Di isopropyl ether
Di isopropyl ether loss
20
30
480
18
423
Carbon
15
4690
2750
Water
Dimethyl formamide
Dimethyl formamide
loss
Dist. Residue
Total
11
Total
131
395
390
916
9206
Output
Step-1
Ethanol Recover
Ethanol Loss
Hexane Recover
Hexane Loss
Dist. Residue
Total
Quantity
(Kg)
300
378
15
375
15
2
916
3470
383
10
10
9206
15. COLESEVELAM
Manufacturing Process
Stage-1 Preparation of Polyallylamine
Into clean reactor charge 301 Kg Concentrated hydrochloric acid at room temperature.
Add 156 Kg
Monoallylamine in 2 hrs at 5 to 10ºC. Raise the temperature and distill out water and excess hydrochloric
acid under vacuum at below 60ºC. Add 95 Kg Water into the mass at room temperature. Raise the mass
temperature to 45 to 50ºC and add a solution of 2,2-dimethyl-2,2-azopropane dihydrochloride (3 Kg in 10
Kg water) at 45 to 50ºC.
Stir the mass 30 hrs at 45 to 50ºC. Monitor the reaction performance by
analytical methods. After completion of reaction, cool the mass to 25 to 30ºC and transferred into 1354 Kg
Methanol. Stir for 1 hr at 25 to 30ºC.
Filter the slurry and wash the material with 395 Kg Methanol.
Collect the main and washing Mother Liquor together.
Unload and dry the material at 45 to 50ºC in
vacuum tray drier (VTD) till to reach the required LOD (Loss On Drying) of the product.
Expected weight is 245 Kg.
Stage-2 Preparation of Colesevelam
Add 200 Kg Sodium hydroxide solution (50 Kg in 150 Kg water)
temperature and stir for 30 minutes.
into 245 Kg Polyallylamine at room
In a separate reactor, add 2 Kg of Epichlorohydrin, 4 Kg n-
Decylchloride and 4 Kg Trimethyl ammonium hexylchloride into 63 Kg of above solution and at room
temperature and stir for 20 minutes.
Add this solution into the above remaining mass at 25 to 50ºC in 10
to 20 minutes. Cool to 30ºC and stir for 30 minutes at 25 to 30ºC. Filter the slurry and wash the material
with 32 Kg Methanol, 100 Kg Water, 20 Kg Sodium hydroxide solution (1Kg in 19 Kg Water) and finally with
400 Kg Water. Collect the main and washing Mother Liquor together. Unload and dry the material at 45 to
50ºC in vacuum tray drier (VTD) till to reach the required moisture content of the product.
Expected weight is 260 Kg.
Chemical Reaction
Stage – 1 (Preparation of Polyallylamine)
NH2
H2C
+
HCl
Hydrochloric acid
Monoallylamine
Polymerisation
45 to 50ºC
Water
.
.
.HCl
NH2
n
Polyallylamine Hydrochloride
Stage-2 (Preparation of Colsevelam HCl)
.
.HCl
.
NH2
n
+ NaOH +
Polyallylamine Hydrochloride
O
H3C
Cl
+
Epichlorohydrin
+
n-Decyl chloride
CH3
+
N
Cl
H3C
Trimethylammoniumhexylchloride
Cross Linking
25 to 50ºC
CH3
H2C
NH
N
H3C
H2C
+
CH3
NH
CH3
O
H2C
NH2
Cl
.HCl
n
Colesevelam Hydrochloride
Mass Balance:
Sr. Input
No.
Step-1
1
Monoallylamine
2
2,2-dimethyl-2,2azopropane
dihydrochloride
3
Concentrated
Hydrochloric acid
4
Methanol
5
Water
Total
Quantity
(Kg)
Sr. Input
No.
Step-2
1
Polyallylamine
2
Epichlorohydrin
3
n-Decylchloride
4
Trimethylammoniumh
exylchloride
5
Sodium hydroxide
6
Methanol
7
Water
8
9
10
11
Total
Quantity
(Kg)
156
Output
Step-1
Methanol Recover
Quantity
(Kg)
245
1696
3
301
1749
105
2314
245
2
4
4
Methanol Loss
52
Effluent
321
Total
2314
Output
Quantity
(Kg)
Product
Efflunet
Sodium chloride
Methanol
260
788
172
32
Total
1252
116
32
849
1252
16. Glimepiride
Manufacturing Process
•
Charged 3 Ethyl 4 methyl Pyrroline and toluene is SSR. Charged slowly 2 Phenyl Isocyante in it. Heat the
RM to reflux for 2 hrs.
•
Cool and then chilled the rm. Filter the mass and dry it.
•
Charged Chloro Sulfonic Acid in Reactor at RT and chilled it. Charged Amide derivative in above reaction
mixture in chilling condition.
•
The reaction mixture was heated and stirred. The reaction mixture was very slowly quenched in chilled
ammonia solution. Filter the solid mass, wash with water and dry it.
•
Charged EDC and above crude product in Reactor at RT. The reaction mixture was heated and stirred
the chilled to 0-5oC. Filter the solid mass under chilling condition and dry it.
Chemical Reaction:
Mass Balance:
Sr. Input
No.
1
3 Ethyl methyl Pyrroline
2
2 Phenyl ethyl
isocyanate
3
Toluene
4
Chloro Sulfonic Acid
5
Ammonia Solution
6
EDC
7
Water
Total
Quantity (Kg)
Output
Quantity (Kg)
0.40
Product
1.00
0.40
Toluene Recover
3.35
3.50
1.00
3.10
2.00
1.00
11.29
EDC Recover
Distillation + Drying loss
Residue
Effluent
1.70
0.83
0.03
4.38
Total
11.29
17. Furosemide
Manufacturing Process:
To Furfurylamine, 2,4-Dichloro-5-Sulfamoyl Benzoic acid (Lasamide) will be added below 60°C. Gradually,
temperature of the reaction mixture, under Nitrogen atmosphere will be raised to 117- 120°C and
maintained for several hrs. The reaction mass will be cooled and passing of Nitrogen gas will be stopped
and diluted with Isopropyl Alcohol. Subsequently the pH of reaction mass will be adjusted to highly alkaline
with solution of sodium hydroxide & cooled to 0°C for several hours. When the crude sodium Frusemide
separates out, it will be centrifuged. The sodium salt of Frusemide will be dissolved in DM water,
charcolised and filtered. pH of clear solution will be adjusted to acidic when pure Frusemide separates out.
It will be centrifuged, washed with DM water & dried. Dried product will be milled blended, shifted and
packed.
Chemical Reaction:
Mass Balance:
Sr. Input
No.
1
Furfuryl Amine
2
Lasamide
3
Caustic Flake
4
IPA
5
Carbon
6
Water
7
Acetic Acid
8
Total
Quantity
(Kg)
1564
850
234
5920
80
7396
220
16263
Output
Product
Furfuryl Amine
Recover
Loss
Dist. Residue
Spent Carbon
Effluent
IPA Recover
IPA Loss
Total
Quantity
(Kg)
1000
1210
450
20
70
7593
5680
240
16263
18. BETAHISTINE DIHYDROCLORIDE:
MANUFACTURING PROCESS:
2-vinyl pyridine react with methylamine hydrochloride in presence of acetic acid to form betahistidine Base
isolated by high vacuum distillation. Betahistidine Base react with IPA Hcl to form Betahistidine
dihydrochloride.
CHEMICAL REACTION:
N
+ H3C
CH3
NH2 HCl
CH3
N
NH
Molecular Formula: C7H9N
Molecular Formula: CH6ClN
Formula Weight:
107.15306 Formula Weight:
67.51804
CH3
N
Molecular Formula: C8H12N2
Formula Weight:
136.19428
2 HCl
IPA HCl
NH
CH3
N
NH
Molecular Formula: C8H12N2
Formula Weight:
136.19428
Molecular Formula: C8H14Cl2N2
Formula Weight:
209
Mass Balance:
Sr.
No.
Input
Quantity (Kg)
Output
Quantity (Kg)
1
2
3
4
5
6
7
8
Total
2- vinyl pyridine
Methylamine hydrochloride
water
Chloroform
Sodium hydroxide
Acetic Acid
IPA
IPA HCl(20%)
0.63
0.80
0.31
3.13
0.45
0.06
2.50
1.38
9.25
Product
Effluent
Chloroform Recovery
Chloroform Loss
IPA Recovery
IPA Loss
Distillation residue
1.00
2.22
2.90
0.23
2.40
0.10
0.40
Total
9.25
19. Adapalene
Manufacturing Process:
Charge THF & start nitrogen purging until water quenching. Charge Mg turnings. Heat the mass up to reflux
60-65°C . Prepare solution of adamentanol & p- bromomphenol in MDC inn a clean container. Add above
prepared solution through the addition funnel in 10 – 15 min at 60-65°C. Prepare solution of Adamentanol
in MDC in clean container. Add above prepared solution of in THF in 45-60 min at 60-65°C. Reflux the
reaction mass for 60 min. Cool the reaction mass. Charge MDC to the reaction mass. Cool the reaction
mass. Charge 6-Bromo-2-methyl naphthoate at 15-20°C. Maintain the reaction mass for 30 min at 40- 45°C.
Take purified water in RBF & cool it 20-25. Prepare HCl water solution Add the HCl water solution slowly.
Stir the reaction mass. Wash with purified water. Suck dry well. Unload the material of crude stage C wet
cake & take for purification. Dry the wet cake at 70 – 75°C.
Chemical Reaction:
Step-2
Step-3
Step-4
Mass Balance:
Sr.
No.
Input
1
2
3
4
5
6
7
8
Total
Adamentanol
Para Bromo Phenol
THF
Mg Turning
MDC
6-Bromo-2-methyl naphthoate
HCl
Water
Quantity (Kg)
24
15
30
3
68
36
66
350
592
Output
Product
Effluent
MDC Recovery
MDC Loss
THF Recovery
THF Loss
Distillation residue
Total
Quantity (Kg)
50
442.5
65
2
29
0.5
3
592
20. TELMISARTAN AND ITS INTERMEDIATE
Manufacturing Process:
4-Amino-3-benzoic acid is esterifies to gives methyl-4-amino-3-bezoate, which reacted with butryl chloride
to produce butyramide derivative, which nitrated with fuming nitric acid to produced nitro derivative,
which reduced in presence of Palladium on charcoal and then hydrolyzed to gives Benzimidazole derivative.
Benzimidazole is reacted with n-methyl o-pheniline Diamine to gives condensed product, which is reacted
with bromo ester to gives telmi ester, which hydrolyzed with potassium hydroxide to gives Telmisartan.
Chemical Reaction:
CH3
CH3
NH2
NH2
CH3OH/H2SO4
HO
H3C
O
65°C
O
O
M wt - 165
TS-1
TS-1
Yield 94 %
O
O
CH3
CH3
O
NH2
H3C
NH
H3C
O
Cl
H3C
O
TEA/MDC
0 to 5°C
Yield 96 %
O
CH3
O
M wt - 235
TS-2
O
CH3
O
NH
H3C
NH
Fuming HNO3
CH3
CH3
O
-20 to -25°C
Yield 93 %
H3C
O
NO2
O
M wt - 280
TS-3
O
NH
O
CH3
O
CH3
H3C
CH3
CH3
Pd/Charcoal
Acetic Acid
H3C
H
N
O
N
80°C
NO2
CH3
O
O
M wt - 232
TS-5
CH3
CH3
H
N
10% NaOH Sol.
H
H
N
O
CH3
N
H3C
O
N
CH3
Methanol
O
Yield 86 %
M wt - 218
TS-6
O
Polyphospheric Acid
CH3
H
N
140 to 145°C
CH3
CH3
H
N
N
N
H
O
N
N
CH3
NH2
O
NH
CH3
Yield 96 %
M wt - 304
TS-7
CH3
Mass Balance:
Qty (Kg)
INPUT
Raw material
3.53
1.484
Methanol
4-Amino 3-Methylbenzoic acid
1.423
Conc. Sulphuric acid
2.968
Liq. NH3
9.410
Total
OUTPUT
Material
Qty(Kg)
TS-01
ML to ETP
7.574
Output
Loss
INPUT
Qty (Kg)
1.53
5.670
Raw material
TS-1
MDC
OUTPUT
Material
TS-02
Soduim Sulpahte
Aqs. Layer
1.314
1.287
0.153
0.387
12.240
5.094
TEA
Butryl chloride
Sodium Bicarbonate
Sodium Sulphate
Water
Hexane
Recovered MDC+Hexane
ML to ETP
27.675
Total
Output
Qty(Kg)
0.387
12.240
6.084
7.705
Loss
Qty (Kg)
0.90
4.050
0.090
9.000
14.040
INPUT
Raw material
TS-2
Fuming Nitric acid
Sodium Bicarbonate
DM Water
Total
1.53
0.31
OUTPUT
Material
0.90
0.359
Qty(Kg)
TS-03
ML to ETP
12.748
Output
Loss
1.00
0.292
21. Tapentadol Hydrochloride
Manufacturing Process:
• Charge isopropyl alcohol, 3-methoxy propiophenone, dimethyl amine hydrochloride,
Paraformaldehyde. Heat the reaction mass. Maintain the reaction mass and distill out isopropyl alcohol.
Charge Purified water and sodium hydroxide.
• Charge dichloromethane and separate out layers. Charge dichloromethane layer into the reactor and
distill out dichloromethane. Charge IPA and charge L (-) Dibenzoyl tartaric acid. Maintain the reaction
mass and filter it. Charge Purified water and above wet cake.
• Charge sodium carbonate and Dichloromethane. Separate out layers. Charge dichloromethane layer
into the reactor and distill out dichloromethane and charge Tetrahydrofuran. Charge magnesium
turning and ethyl acetate. Maintain the reaction mass and distill out Tetrahydrofuran. Charge Purified
water and Acetic acid. Add ammonium solution and Dichloromethane. Stir the reaction mass and
separate out layers. Charge Product layer into a reactor and distill out dichloromethane. Charge Ethyl
acetate into the above reactor and cool the reaction mass. Charge Trifluoroacetic anhydride and
maintain the reaction mass. Unload the reaction mass.
• Charge palladium and apply hydrogen pressure. Maintain the reaction mass. Filter the reaction mass
and collect filtrate. Charge hydrobromic acid into the reaction mass. Heat the reaction mass and
maintain the reaction mass charge ammonia solution and ethyl acetate. Separate out layers. Distill out
ethyl acetate and charge Isopropyl alcohol. Add IPA HCl. Maintain the reaction mass. Centrifuge the
reaction mass.Dry it to give Tapentadol Hydrochloride.
Chemical Reaction:
Mass Balance:
Sr. No.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
Total
Input
3-methoxy propiophenone
IPA
Dimethyl Amine HCL
Paraformadehyde
Sodium Hydroxide
MDC
L (-) Dibenzoyl tartaric acid
THF
Mg Turning
Ethyl Bromide
Acetic Acid
Ammonium Solution
Ethyl Acetate
Trifluroacetic anhydride
Palladium
Acetone
HBr
IPA HCl
Water
Quantity (Kg)
1.412
7.530
1.059
0.588
0.376
10.00
1.412
3.530
0.171
0.588
0.118
0.506
5.883
0.882
0.070
6.470
1.765
0.882
17.647
60.889
Output
Product
IPA Recover
IPA Loss
MDC Recover
MDC Loss
THF Recover
THF Loss
Ethyl Acetate Rec.
Ethyl Acetate Loss
Palladium Recover
Palladium Loss
Acetone Recover
Acetone Loss
Effluent
Dist. Residue
Process Waste
Loss
Total
Quantity (Kg)
1.00
7.15
0.35
9.60
0.35
3.42
0.08
5.65
0.23
0.06
0.01
6.21
0.26
25.827
0.407
0.235
0.05
60.889
22. Colistimethate Sodium
Manufacturing Process:
Stage 1:
Take Colistin sulphate and water. Filter and remove insoluble material. Charge sodium bi carbonate
solution. Add sodium carbonate for adjusting pH. Get white precipitation.
Add 400 ml sodium bi carbonates solution. Add dematerialized water and adjust pH by adding sodium
carbonate. Continue stirring 2 hours. Filter the reaction mass under nitrogen gas. Unloaded wet cake and
charge dematerialized water. Add slowly sodium bi sulfite solution for adjust pH. Maintain 1 hour. Add
remaining solution in reaction mass for pH. Stirring for 2 hours. Add acetic acid. Adjust pH. Stir for 1 hour.
Add industrial solvent. Start a zeotropic distillation. Strip out 2 times from industrial solvents. Thick slurry
mass is obtained. Add acetone for make free flowing slurry. Maintain 6 hours. Filter and unload wet cake.
Dry under vacuum.
Final Stage:
Take crude stage-1 and methanol, add industrial solvent. Filter with flow bed. Wash with methanol. Distill
out methanol under vacuum. Add Industrial solvent under stirring and get uniform slurry. Distill out
methanol under vacuum. After complete distillation, add industrial solvent and maintain for 2 hours at 25
to 30oC temperature. Filter and wash with Industrial solvent. Dry under vacuum at 25 to 30 oC temperature
for 4 hours. After drying continue 6 hours on 45 to 60oC temperature. Getting final material.
Chemical Reaction:
Mass Balance:
Sr. No.
Step-I
1
2
3
4
5
6
7
8
9
Total
Step-II
9
10
11
12
13
Total
Input
Colistin Sulphate
Sodium Bicarbonate
Sodium Carbonate
Formaldehyde
Sodium Bisulfite
Acetic Acid
Solvent
Acetone
Water
Step-I
Methanol
Water
Quantity (Kg)
100
50
25
100
230
12
2100
3400
3000
9017
155
5800
1340
7295
Output
Quantity (Kg)
Step-I
Solvent Recover
Solvent Loss
Acetone Recover
Acetone Loss
Dist. Residue
Effluent
Drying Loss
155
2015
85
3230
170
50
3227
85
Total
9017
Product
Methanol Recover
Methanol Loss
Effluent
Solid Waste
Total
75
5510
250
1430
30
7295
23. ROSUVASTATIN CALCIUM
Manufacturing Process:
Step-I
4-Fluoro-Benzadehyde reacts with 4-Methyl-3-oxo-pentanoic acid ethyl ester in
presence of Base to give Stage-1 as product.
Step-II
Sage-1 product reacts with S-Methyl iso thio urea and 2, 3Dichloro-5, 6-dicyano benzo quinone in presence
of HMPA to give stage-2 as product.
Step-III
Stage-2 product reacts with meta-chloro peroxy benzoic acid to give Stage-4 as
product and Meta chloro benzoic acid as by-product.
Stage-4
Stage-3 product reacts with methyl amine in presence of Ethanol s solvent media to
give Stage-4 as product.
Stage-5
Stage-4 product reacts with Methane sulfonyl chloride in presence of Sodium hydride
as catalyst to give Stage-5 as product.
Stage-6
Stage-5 product undergoes reduction and oxidation in presence of Hydrogen gas to
give Stage-6 as product.
Stage-7
Stage-6 product reacts with methyl (3R)-3-(ert-butyldimethylsilyloxy)-5-oxo-6triphenylphosphoranylidene hexanoate.
Stage-8
Stage-7 product reacts with Hydrogen fluoride in presence of Acetonitrile as solvent
media to give Stage-8 as product.
Stage-9
Stage-8 product reacts with Sodium Boro hydride undergoes hydrogenation to give
Sage-9 as product.
Stage-10
Stage-9 product reacts with Calcium chloride undergoes saponification to give
Rosuvastatin Calcium as product.
Chemical Reaction:
Mass Balance
24. 1,3 Di Chloro Acetone
Manufacturing Process:
Stage-I
Add Epichlorohydrin (500 kg) in Glass Line Reactor and cool to 0'C to 5"C
5"C.'
Now addn 30% HCl(1200kg )within i0to12hrs
0to12hrs when temperature is between 0'C to 5"C'
After this separate the 20% solution of Spent Hydrochloric Acid (Qty: 12) kg) and
organic layer containing 1,3-Dichloro-2--Prolmnol (480.0 kg)
Stage-II
Now charge 1,3.Dichloro-2.Propanol (480
480 kg) and Sodium Dichromate solution (1500
kg) 1 in Glass Line Reactor and Cool to 10"C - 18"C
Then slowly add 70% solution of Sulphuric Acid (1000kg) within 10 to 15 hrs when
temperature is 10"C to 18"C.
After this add DM water (500 kg)
g) and Cool to 10"C'
Transfer reaction mass is centrifuge
fuge to separate mother liquor containing 1 &12%
solution of Basic chromium sulphate (3046 kg) and crude 1,3 Dichloroacetone (434 kg).
Take crude 1,3-Dichloroacetone
Dichloroacetone in Glass Line Reactor and heat to 50"c to separate
lower layer containing product 1,3-Dichloroacetone
Dichloroacetone (384 kg) and acidic waste water (50
kg)'
Keep 1,3 Dichloroacetone in clean HDPE carboy and cool it to soc for 5-6 hrs for solidification.
Chemical Reaction:
Mass Balance:
Sr.
No.
1
2
Input
Epichlorohydrin
HCl (30%)
Qty
(kg)
500
1200
3
Sulfuric Acid (98%)
715
4
5
Sodium Dichromate
Water
Total
600
1685
4700
Output
Product
Dil. HCl
Basic Chromic
Sulphate
Qty
(kg)
384
1220
3046
Effluent
50
Total
4700
25. GUANYL THIOUREA
Manufacturing Process:
Charge water and dicynadiamide at room temperature. Charge phosphourous penta sulphide and sodium
hydro sulphite at room temperature. heat it to 45 °c to 55 °c and maintain the temperature till reaction
complite. Cool and centrifuge. Wet cake dry in dryer and pack. Mother liquor is di – potassium phosphate
which is selling in liquid form.
Chemical Reaction:
NH
H2N C N C
H2N
N + P2S5
C N C NH2 + 2H3PO4 + 4H2S + KOH + H2O
H
2H3PO4 + KOH + H2O
S
HN H
POTASSIUM SULPHATE
Material Balance
Sr.
No.
Input
Qty
(kg)
Output
1
Phosphorus Penta
Sulphide
182
2
3
KOH
Dicyanadiamide
220
200
4
5
6
Sodium Hydro Sulphite
Water
Total
Qty
(kg)
Product
Di Potassium
Phosphate
Drying Loss
220
40
300
HCl Gas
323
942
Total
942
384
15
26. Rabeprazole Sodium
Manufacturing Process:
Stage-1
2, 3-Lutidine is reacted with Hydrogen Peroxide in presence of Acetic Acid to give N-Oxide it further reacts
with Nitration mixture (Nitric Acid + Sulfuric Acid) to give Stage-1
Stage-2
Stage-1 is reacted with 3-Methoxy-1-Propanol and Sodium Hydroxide to get Stage-2 Compound
Stage-3
Stage-2 Compound is reacted with Acetic Anhydride, Sodium Hydroxide and
Hydrochloric Acid to get Stage-3 Compound
Stage-4
Stage-3 Compound is reacted with Thionyl Chloride, 2Mercapto benzimidazole and sodium hydroxide in the
presence of MDC as a solvent media to give tage-4 as product.
Stage-5
Stage-4 Compound is reacted with Sodium Hypochlorite to get Rabeprazole Base
Stage-6
Stage-5 reacts with Sodium hydroxide to get Rabeprazole Sodium
Chemical Reaction:
Mass Balance:
27. Carvedilol
MANUFACTURING PROCESS
Guiacol is condensed with Ethylene Dichloride to give 2-(2-Methoxyphenoxy)ethyl Chloride(CV-1). CV-1 is
reacted with Pthalimide to give 2-(2-methoxyphenoxy) ethyl phthalimide (CV-2). Dephthaloylation and
treatment with HCl gives 2-(2-methoxyphenoxy) ethyl amine hydrochloride(CV-3 HCl) , which is further
basified to give 2-(2-methoxyphenoxy)ethyl Amine (CV-3).
Simultaneously 1,3 Cyclohexandione is reacted with phenyl hydrazine to give 1,3 cyclohexandione mono
phenyl hydrazone (CV-4). CV-4 was cyclized under acidic conditions to give 1,2,3,4-tetrahydrocarbazol-4one(CV-5). Catalytic aromatization of CV-5 gives 4-hydroxy-9-(H) carbazole (CV-6). CV-6 is further reacted
with Epichlorohydrin to give 4-oxyranylmethoxy-9-(H)-carbazole(CV-7).
CV-7 and CV-3 are then reacted together to give crude CV-8. It is then purified to get Carvedilol.
Chemical Reaction:
Synthetic Route of Carvedilol
O
O
N
H
CV 7
O
Dioxane
NH 2
OCH 3
CV 3
Toluene:Cyclohexane:Ethyl acetate (60:19:21)
OH
O
O
NH
H 3 CO
Carvedilol (CV )
Mass Balance
28. Celecoxib
Manufacturing Process
•
Charged water in Reactor at RT. Charged 4 SPH and Dione Deri in Reactor. The reaction mixture was
heated and stirred well. Cool the RM and Filter the Product.
•
Charged Toluene and wet cake in above reactor again. Heat the RM and stir well for several time.
The organic layer were washed with water add Activated carbon at stirred under heating.
•
Filter the RM with Sparkler. The filtrate was cooled. The separated solid was filtered and dried
Chemical Reaction:
Mass Balance:
Sr.
No.
Input
1
2
3
4
5
6
Total
4 SPH
Dione Deri
Toluene
Carbon
Water
Quantity (Kg)
Output
Quantity (Kg)
0.70
0.65
2.80
0.01
1.60
Final Product
Toluene (Recd)
Distillation + Drying Loss
Residue
Carbon Waste
Effluent
1.00
2.65
0.19
0.03
0.02
1.88
5.77
Total
5.77
29. CLOPIDOGREL BISULPHATE
MANUFACTURING PROCESS:
STAGE 1:
• Starting materials amino(2-chlorophenyl)acetic acid ,methanol, Sulfuric acid are added into the reaction
vessel and agitated until reaction is completed.
•
Methanol is recovered from the reaction mass by distillation and some of the same is lost as vapor
during the operation.
•
Water and Dichloro methane are added into the reaction mass and adjust PH to neutral with liquor
ammonia.
•
Two layers namely MDC layer and aqueous layer are obtained.
•
Aqueous layer is sent to ETP.
•
MDC (Dichloro methane) layer is then distilled to recover MDC wherein vapor loss occurs during the
operation.
•
Stage 1 product is further isolated by continuing distillation.
STAGE 2:
• Starting materials thiophene-2-ethanol, toluene, p – toluene sulphonyl chloride, water, sodium
hydroxide solution are added into the reaction vessel and stirred until reaction is completed.
•
Two layers toluene layer and aqueous layer are obtained. Aqueous layer is further sent to ETP.
•
Toluene layer is then distilled to recover toluene wherein vapor loss occurs during the operation.
•
Stage 2 product is further isolated by continuing distillation.
STAGE 3:
• Starting materials Stage 1 product, stage 2 product, acetonitrile, dipotassium phosphate are added into
the reactor and stirred until the reaction is completed.
•
Acetonitrile is recovered from the reaction mass by distillation and some of the same is lost as vapor
during the operation.
•
Ethyl acetate is added into to the reaction mass and agitated to clear solution.
•
Further water is added to obtain layer separation.
•
Two layes namely ethyl acetate layer and water layer are obtained. And water layer is sent to ETP.
•
Further conc. Hydrochloric acid is added to the ethyl acetate layer for precipitation and then filtered
through centrifugal filter.
•
The wet cake so obtained is dried to obtain final product.
•
Filtrate is then distilled to obtain ethyl acetate and remaining effluent is sent to ETP.
STAGE 4:
• Starting materials couple ester, water, paraformaldehyde is charged into the reaction vessel and is
agitated.
•
Further dichloro methane and water are added to the reaction mass and then adjust PH acidic with
liquor ammonia.
•
Namely MDC layer and water layer are obtained.
•
Water layer is sent to the ETP.
•
MDC layer is then distilled to recover MDC. Wherein vapor loss occurs during the operation.
•
Stage 1 product is further isolated by continuing distillation.
STAGE 5:
• Starting raw materials stage 4 product, acetone, Tartaric Acid are charged into the reaction vessel and
are stirred for longer time.
•
Entire mass is then filtered by centrifugal filter and wet cake so obtained is dried to obtain dry cake..
•
The filtrate is sent for solvent recovery.
•
Water and dichloro methane are charged into the reaction vessel & then dry cake obtained is charged.
•
Further PH is adjust to alkaline by sodium carbonate solution to obtain layer separation.
•
Namely MDC layer & water layer are obtained.
•
Water layer is sent to ETP.MDC layer is then distilled to recover MDC wherein vapor loss occurs during
the operation.
•
Stage 2 products are further isolated by continuing distillation.
STAGE 6[Final]:
• Stage 2 product, acetone, activated carbon are charged into the reaction vessel and entire mass of the
reaction vessel is filtered through the neutch filter.
•
Further con. Sulfuric acid is added slowly to the reaction mass for crystallization.
•
It is further filter through centrifugal filter.
•
The wet cake so obtained is dried to obtain final product.
•
The filtrate is used in next batch for obtaining second crop.
•
The dried product is finally packed.
CHEMICAL REACTION:
STAGE 1:
O
OH
O
Cl
O
Cl
CH3
Methanol/H2SO4
NH2
NH2
amino(2-chlorophenyl)acetic acid
methyl amino(2-chlorophenyl)acetate
STAGE 2:
CH3
+
OH
S
O
S
Cl
Thiophene-2-Ethanol
para toluene sulphonyl chloride
O
H3C
O
S
O
O
S
Chloro phenyl glycine methyl ester tartarate salt
STAGE 3:
O
O
Cl
O
CH3
H3C
S
+
NH2
O
O
S
2-(2-thienyl)ethyl 4-methylbenzenesulphonate
methyl amino(2-chlorophenyl)acetate
Ethyl acetate/HCL
Cl
O
O
NH
.HCL
H3C
S
methyl (2R)-(2-chlorophenyl){[2-(2-thienyl)ehtyl]amino}acetate hydrochloride
STAGE -4 :
Cl
Cl
O
P-Formaldehyde
O
N
NH
O
H3C
O
S
H3C
S
methyl (2-chlorophenyl)(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)acetate
stage 3
STAGE – 5 :
Cl
O
Cl
Tartaric Acid
O
N
N
O
O
H3C
S
Stage 4
H3C
S
methyl (2R)-(2-chlorophenyl)(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)ethanoate
STAGE – 6:
Material Balance:
S-r
No. Material INPUT
STAGE 1
amino(2-chlorophenyl)acetic
1 acid
2 methanol
3 Potassium salt
4 Water
5 MDC
6 Liq. ammonia
TOTAL
1
2
3
STAGE 2
Thiophene-2-Ethanol
p-toluene sulphonyl chloride
Toluene
Qty(in
kg)
1.25
3.95
0.7
5.30
4.98
0.62
16.80
0.5
1.05
3.12
Sr
No.
Material OUTPUT
1
2
3
4
5
6
Recovered Methanol
Loss Methanol
Recovered MDC
Loss MDC
ML to ETP
Stage 1 Output
TOTAL
1 Recovered Toluene
2 Loss Toluene
3 ML to ETP
Qty(in
kg)
3.75
0.20
4.48
0.5
6.87
1.00
16.80
2.93
0.16
6.30
4
5
1
2
3
4
5
6
7
1
2
3
4
5
1
2
3
4
5
6
1
2
3
4
Water
Sodium hydroxide
4.5
1.25
TOTAL
10.42
STAGE 3
Stage 1
Stage 2
Acetonitrile
Dipotassium phosphate
Ethyl acetate
water
HCL
TOTAL
1.25
1.00
6.30
0.87
5.60
2.00
0.85
17.87
STAGE 4
Stage 3
Water
P-Formaldehyde
MDC
Liq. Ammonia
1.50
12.00
0.53
11.9
0.60
TOTAL
STAGE 5
Stage 4
Acetone
Tartaric acid
Water
MDC
Sodium carbonate
TOTAL
4 Stage 2 Output
5 Residue
1
2
3
4
5
6
7
1
2
3
4
26.53
1.10
11.00
0.82
2.70
6.65
0.70
22.97
STAGE 6
Stage 5
Acetone
Activated carbon
Sulfuric acid
1.00
4.74
0.15
0.31
TOTAL
6.20
1
2
3
4
5
6
1
2
3
4
1.00
0.03
TOTAL
10.42
Recovered Acetonitrile
Loss Acetonitrile
Recovered Ethyl acetate
Loss Ethyl acetate
ML to ETP
Residue
Stage 3 Output
TOTAL
5.98
0.32
5.26
0.28
4.97
0.06
1.00
17.87
Recovered MDC
Loss MDC
ML to ETP
Stage 4 product
10.71
1.19
13.53
1.10
TOTAL
26.53
Recovered Acetone
Loss Acetone
Recovered MDC
Loss MDC
ML to ETP
Stage 5 Output
TOTAL
9.90
1.10
5.98
0.67
4.32
1.00
22.97
Recovered Acetone
Loss Acetone
Spent carbon
Stage 6 Output
4.50
0.24
0.46
1.00
TOTAL
6.20
30. ATORVASTATIN
MANUFACTURING PROCESS
Stage: 1 Preparation of (5R)-1,1-Dimethylethyl 6-Cyano-5hydroxy 3-oxo-hexanoate (ATVS1) (R)-4Cyano-3hydroxy butyric acid, ethyl ester is reacted with tert butyl acetate in the presence of LDA at low temp to get
ATVS1.
Stage: 2 Preparation of [R-(R*, R*)]-1, 1-Dimethylethyl 6-Cyano-3, 5-dihydroxy hexonate (ATVS2), ATVS1 is
reacted with Sodium Borohydride in THF and MeOH in the presence of Diethyl Methoxy Borane. After
completion of reaction, reaction mass is quenched with acetic acid. After work up affords ATVS2.
Stage: 3 Preparation of (4R-Cis)-1, 1-Dimethylethyl 6-Cyanomethyl-2, 2-dimethyl-1, 3-dioxane-4-acetate
(ATVS3), ATVS2 is reacted with Acetone in presence of Methane Sulphonic Acid using 2,2- Di Methoxy
propane. And then it is neutralized with 5% NaHCO3 solution then extracted with Ethyl Acetate. After
distillation of Ethyl Acetate MeOH & Water to get ATVS3.
Stage: 4 Preparation of (4R-Cis)-1,1-Dimethylethyl 6-(2-amino ethyl)-2,2-dimethyl-1, 3-dioxane-4acetate (ATVS4), ATVS3 is reduced with Methanolic Ammonia in presence of Raney Nickel and Hydrogen
gas, then catalyst is filtered off and the filtrate is concentrated to give oily mass ATVS4.
Stage: 5 Preparation of [R-(R*, R*)]-2(4-Fluorophenyl)-β, 8-dioxane-5-(1-methylethyl)-3-phenyl-4[(phenyl amino)Carbonyl]-1H-Pyrrol-1tert –butyl heptanoic ester (ATV8), ATVS4 is condensed with (+) 4fluoro-α-2-methyl-1-oxopropyl]χ-oxo-N-β- Diphenyl-benzene butane amide in presence of Pivalic acid
using Toluene, Heptane and THF at. After completion of reaction work up is done with 0.1N NaOH &
0.1N HCl. Organic layer is evaporated which is crystallized in IPA and Water to get ATV8.
Stage: 6 Preparation of Atorvastatin Calcium
Acidic and basic hydrolysis of ATV8 with HCl and NaOH gives sodium salt of Atorvastatin, which is
treated with Aqs Calcium Acetate to give Atorvastatin Calcium in Aqs Methanol.
CHEMICAL REACTION
MATERIAL BALANCE
Sr.
No.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
Particular
Input Qty Sr.
(kg)
No.
Ethyl-4-Cyano-3-hydroxy butanaote
1.00 1
THF
17.567 2
Diisopropyl amine
1.22 3
N-Butyl Lithium
13.60 4
Tert-Butyl acetate
1.68 5
HCl
0.76 6
Ethyl Acetate
31.57 7
NaCl
1.20 8
Methanol
25.243 9
DEMB (50 % Soln)
0.70 10
Sodium Borohydride
0.44 11
Acetic Acid
0.98 12
Dimethoxy Propane
1.81 13
Methane Sulphonic Acid
0.03 14
Sodium Bicarbonate
2.00 15
n-Hexane
5.20 16
DM Water
22.38 17
18
19
20
21
22
Raney Nickel
Pivalic Acid
Toluene
Activated Carbon
Methyl Tert Butyl
Total
1.00 18
0.240 19
9.379
0.100
7.410
145.496
Particular
Output Qty
(kg)
Product
1.85
THF Recovered
17.04
THF Loss
0.527
N-Butyl Lithium Recovery
12.92
N-Butyl Lithium Loss
0.68
H2 gas
0.09
Spent Catalyst
1.5
Spent Carbon
0.05
Ethyl Acetate Recovered
30.94
Ethyl Acetate Loss
0.63
Methanol Recovered
24.61
Methanol Loss
0.63
n-Hexane Recovered
5.12
n-Hexane Loss
0.08
Toluene Recovered
9.19
Toluene Loss
0.189
Methyl
Tert
Butyl
7.04
Recovered
Methyl Tert Butyl Loss
0.37
Effluent
32.04
Total
145.496
31.ETORICOXIB
Manufacturing Process
Ketosulfone is reacted with CPT-Phosphate in presence of Potassium tert-Butoxide in Tetra hydrofurane to
give Etoricoxib crude .Etoricoxib crude recrystallized from IPA-Hexane to give Etoricoxib
Chemical Reaction
Stage-I: Preparation 2-chloro malonaldehyde from sodium salt of 2-chloromalonaldehyde
Stage-II: Preparation 3-amino-2- chloroacrolien from 2-chloro-malonaldehyde
Stage-III: Preparation of Etoricoxib hydrochloride
Stage-IV: Preparation of Etoricoxib (API)
Material Balance
Sr.
Input
No.
Acetic Acid
1
Acetone
2
Ammonia Solution
3
CPT-Phosphate
4
5
6
7
8
9
10
11
12
13
14
15
D M Water
Hydroxylamine Hydrochloride
Hyflow
Isopropyl Alcohol
Ketosulfone
Methanol
Potassium Tertrabutoxide (KTB)
Sodium Acetate
Sodium Hydroxide
Toluene
THF
Trifluro Acetic Acid
Activated Carbon
Hexane
Total
Qty
(kg)
1.520
2.80
5.80
1.520
26.00
0.115
0.177
10.00
0.574
10.00
0.664
0.297
2.153
55.000
23.00
0.465
0.022
0.250
139.357
Output
Etoricoxib
Acetone Recovery
Acetone Recovery Loss
Isopropyl Alcohol Recovery
Isopropyl Alcohol Recovery
Loss
Methanol Recovery
Methanol Recovery Loss
Toluene Recovery
Toluene Recovery Loss
Qty
(kg)
1
2.657
0.124
9.500
0.450
9.65
0.35
53.5
1.25
Aqueous Effluent
Spent Carbon
Dist. Residue
THF Recover
THF Loss
37.054
0.022
0.5
22
0.8
Total
139.357
32. VALSARTAN
Manufacturing Process
There are following steps involved in the synthesis of Valsartan.
Step - 1: - Preparation of L- METHYL VALINATE
L- Valine is treated with methanol in presence of Thionyl chloride to get L- Valine methyl ester which was
then neutralized with alkali solution to get L-methyl valinate.
Step - 2: - Preparation of VALSARTAN OXALATE
L- Methyl valinate is condensed with 4- bromo methyl -2 - cyano biphenyl in presence of potassium
carbonate which was then treated with oxalic acid to isolate the Valsartan oxalate.
Step - 3-A: - Preparation of VALEROYL VALSARTAN
The Valsartan oxalate is condensed with Valeroyl chloride in presence of potassium, Carbonate in o- xylene
to get Valeroyl Valsartan.
Step - 3-B and 3-C: - Preparation of CRUDE VALSARTAN
The cyano group of Valeroyl Valsartan is cyclized in presence of tri butyl tin chloride and sodium azide in oxylene at reflux to get methyl Valsartan. The methyl Valsartan is then hydrolyzed with sodium hydroxide
and isolated with dichloromethane and cyclohexane to get crude Valsartan.
Step - 4:- Preparation of VALSARTAN CALCIUM
The crude Valsartan is treated with calcium hydroxide in acetone and D I water and filtered to obtained
calcium salt of Valsartan.
Step - 5- Preparation of VALSARTAN
Valsartan calcium salt is treated with hydrochloric acid in ethyl acetate and water. The ethyl acetate layer is
treated with diisopropyl ether to obtain the pure Valsartan.
Chemical Reaction
Material Balance
33. Tranexamic Acid
Manufacturing Process:
• In to an Auto clave charge 4-amino methyl benzoic acid.
• Charge Aq. solution of Sodium hydroxide.
• Charge ruthenium and apply hydrogen pressure.
• Heat it and maintain it.
• Filter the reaction mass and collect filtrate.
• Charge Hydrochloric Acid to adjust pH.
• Distill out water.
• Charge methanol and water.
• Maintain it.
• Filter it.
• Dry to give Tranexamic Acid.
Chemical Reaction:
Material Balance
Sr.
No.
1
2
3
4
5
6
Input
4-aminomethyl benzoic
Acid
HCl
Ruthenium
Sodium hydroxide
Methanol
Water
Total
Qty
(kg)
Output
Qty
(kg)
1.060
0.440
0.300
Product
Ruthenium Recover
Methanol Recover
1.000
0.292
1.950
0.252
2.000
7.800
Loss
Effluent
Dist. Residue
Total
0.050
8.51
0.050
11.852
11.852
34. Folic Acid
Manufacturing Process:
Step-I
PABGA, TAPS and TCA are charged in to a reactor containing sufficient water and are stirred maintaining
required pH. The technical folic acid formed is subjected to the next stage.
Step-II
The technical folic acid is treated with acid and is passed through filter press and the solid so obtained is
taken for the next stage.
Step-III
The crude folic acid is dissolved in alkaline solution and is filtered through leaf filter. The folic acid filtrate is
treated with acid and the solid so obtained is subjected to centrifugation.
Chemical Reaction:
o
OH
CH2
H
CO2H
N
O +
CO2H + C
NH2
NH2
H
CH2
H
O
O
N
CO2H
N
N
NH2
H
CO2H
N
N
H
N
H
NH2
N
H2SO4
N
NH2
Mass Balance:
Sr.
No.
1
2
3
4
5
6
7
8
9
10
Input
PABGA
TAPS
TCA
SMBS
NaHCO3
water
HCl 30%
NaOH
Acetic Acid
Total
Qty
(kg)
50
45
32
18
60
580
300
11
16
1112
Output
Product
Solid Waste
Gas Emission
Qty
(kg)
50
93
45
Drying Loss
Effluent
300
624
Total
1112
35. Zolpidic Acid
Manufacturing Process:
Stage 01
Reactor is charged with toluene, 4-methylphenacyl bromide, 2-amino-5-methyl pyridine and tri ethyl amine
and maintained at temp 15-20 0C for 6 hrs. After completion of the reaction, filter the mass, collect the solid
cake and wash the solid with water. Obtain stage 01 product as wet cake which is dried to afford stage 01
product.
Stage 02
Stage 01 product is reacted with, Oxaloyl chloride in presence of MDC as a solvent and TEA as a organic
base at RT temp for 3hrs followed by addition of KOH solution. Then increase the temp of reaction mass up
to 80 0C and simultaneously distill MDC. After complete removal of MDC cool the reaction mass to 60 0C
and add hydrazine hydrate and reflux for 16 hrs. Cool the reaction mass and add KOH. Further increase
temp up to 130 and remove water. Cool the reaction mass and filter; acidify the filtrate with acetic acid.
Collect Crude Zolpidic acid and crystallize in methanol. Dry the product in hot air oven to afford Zolpidic
acid.
Chemical Reaction:
1. Route of Synthesis
Stage – 1: Preparation of Stage 01
O
Br
H 3C
+
N
+
N
N(C 2 H 5 ) 3
Toluene
CH 3
N
H 3C
NH 2
+
N(C 2 H 5 ) 3 . HBr
H 2O
2 - Amino - 5 - methyl pyridine
Triethyl amine
181.9
18
4 - Methyl Phenacyl bromide
2 - (4 - methylphenyl) - 6 - methyl imidazo[1,2 -a] - pyridine
C 6 H 15 N
C 6H 8N 2
C 9 H 9 BrO
C 15 H 14 N 2
+
CH 3
212.9
108
101
222
Stage – 2: Preparation of Zolpidic acid
Cl
O
N
MDC
N
++
(C 2 H 5 )3 N 2 KOH
N
2 x 56 H C
H3C
3
Cl
O
2 - (4 - methylphenyl) - 6 - methyl imidazo[1,2 -a] - pyridine
CH3
C 15 H 14 N 2
O
O
Oxalyl chloride 101
C 2 Cl 2 O 2
222
CH3
N
+
137.5
O
C 17 H 13 KN 2 O 3
+ KCl
74.5
332
N
N
CH 3
N
+
H 3C
H 2N
NH 2
CH 3
N
H 3C
O
O
O
N
K
K
H 2N
O
32
CH 3
N
+ 2 KOH
H 3C
K
346
CH 3
N
Methanol
H 3C
O
2 x 56
O
C 17 H 15 KN 4 O 2
18
N
N
O
H 2O
346
332
N
+
O
C 17 H 15 KN 4 O 2
N 2H 4
C 17 H 13 KN 2 O 3
H2N
18
(C 2H 5) 3 N.HCl
K
127
+ H2O
+
3 CH 3 COOH
Acetic acid
3 x 60
OH
C 17 H 16 N 2 O 2
Zolpidic acid
280
+
N2
+
2 H 2O
28
2 x 18
3 CH 3 COOK
3 x 98
Mass Balance:
Sr.
No.
Input
QTY (Kg)
Output
QTY (Kg)
Toluene
1750
Stage 01
350
350
Recovered toluene
1665
214
Aqueous effluent 1
2485
Step-I
1
2
3
Methyl Phenacyl
bromide
2- Amino-5-methyl
pyridine
4
Triethyl amine
186
Solvent loss
85
5
Water
2100
Distillation residue
15
4600
Total
4600
Total
Step-II
1
Stage 01
350
Zolpidic acid
350
2
Oxalyl chloride
245
Recovered MDC
1680
3
Methylene Dichloride
2100
Recovered methanol
3150
4
Potassium hydroxide
469
Aqueous effluent 2
8423
5
Water
7000
Solvent loss
770
6
Acetic acid
578
Distillation residue
20
7
Hydrazine hydrate
151
8
Methanol
3500
Total
14393
Total
14393
36. PREGABALIN
Manufacturing Process
Sodium Hydroxide solution in Process water is chilled at 0-10°C and then charge R-(-)-3-(Carbamoylmethyl)5-methylhexanoic acid [R-(-)-CMH]. Addition of liquid Bromine is done at 0-5°C then raise the temperature
of the reaction mass up to 30-35°C. After reaction monitoring, raise the temperature of the reaction mass
to 55-60°C and apply carbon treatment. The clear filtrate is then received in another reactor. Excess water
is distilled off from the reaction mass. The reaction mixture is acidified with concentrated Hydrochloric acid.
Reaction mass is then up to 80-85°C and after that gradual cooling to 25-30°C. The material is centrifuged
after maintaining of the reaction mass at 25-30°C for 4-6 hrs.
The dry material is then charged in IPA and raises the temperature to 80-85°C. Add DM water to reaction
mass at 80-85°C. Filter the clear reaction mass and chill it to 8-12°C. The material is then centrifuged and
dried in under vacuum.
Chemical Reaction
Material Balance
Stage - 1
Sr.
No.
1
Raw Material
Quantity Kgs
Process water
Sodium Hydroxide
4-CMH
Liquid Bromine
Activated carbon
Hyflo
Hydrochloric acid
Total
2
3
4
5
6
7
2590.0
347.2
250.0
224.0
12.5
3.0
450.0
3877
Out Put
Quantity Kgs
Spent carbon and
hyflo
Spent ML
Loss on drying
Out Put
Total
28.0
3623.7
62.5
162.5
3877
Stage - 2
Sr.
No.
1
2
3
Raw
Material
Pregabalin
(Stage-I)
IPA
DM water
Total
Quantity Kgs
215.0
1290.0
860.0
2365
Out Put
Spent ML
Loss o Drying
Out Put
Total
Quantity Kgs
2150.00
32.2
182.8
2365
ANNEXURE-4
WATER CONSUMPTION AND WASTE WATER GENERATION (EXISTING AND PROPOSED)
Sr.
Purpose of Water
No.
Consumption
Water Consumption
Waste Water Generation
(m3/Day)
(m3/Day)
Existing
1.
Total after
Existing
Total after
proposed
proposed
expansion
expansion
Industrial
Process
1.0
28
0.6
22
Boiler
0.6
10
Nil
0.5
Cooling Tower
0.5
10
Nil
0.5
Washing
0.4
2
0.4
2
2.5
50
1.0
25
Total (Industrial)
2.
Domestic
1.0
3
0.9
2.4
3.
Gardening
--
1
--
--
3.5
54
1.9
27.4
Total
WATER BALANCE DIAGRAM
Raw Water: 50 KL/Day from GIDC
Domestic
3 KL/Day
2.4 KL/Day
Process
28 KL/Day
22 KL/Day
Septic tank &
soak pit
Boiler
10 KL/Day
Cooling Tower
10 KL/Day
0.5 KL/Day
0.5 KL/Day
ETP: 22 KL/Day
CETP, Ankleshwar
High COD &
High TDS:
KL/Day
Common
MEE,
Ankleshwar
3
Washing
2 KL/Day
2 KL/Day
Gardening
1 KL/Day
ANNEXURE-5
Effluent Treatment Plant (ETP) DETAILS:
Existing:
M/s. Suleshvari Pharma has two (02 nos.) collection tank for high COD and Low COD effluent stream. Raw
effluent from plant separates as high COD and Low COD stream and collects in concern collection tank
where it neutralize and get settles. Neutralized high COD effluent then sends to common MEE facility of
M/s. ETL, Ankleshwar for further treatment and final disposal while low COD sends to CETP operates by
M/s. ETL, Ankleshwar for further treatment and final disposal.
ETP Units Name & Size:
Sr. No.
Unit Name
1
Collection Tank-1
2
Collection Tank-2
Size (m x m x m)
3.0 x 2.5 x 2.0
5.0 KL
Proposed:
Stream I (Low COD & TDS Stream) = 24 KL/Day
First all non-toxic and biodegradable streams (low & medium COD& TDS) of wastewater shall pass through
Screen Chamber (SC-01) where floating material shall be removed with help of Screen (S-01). Then effluent
shall be passed through Oil & Grease Removal Tank (OGRT-01). Automatic mechanical Oil Skimmer shall be
provided in the OGRT to remove floating oil and grease from the wastewater to Oil & Grease Collection
Tank (OGCT-01). Then effluent shall be collected in Collection cum Equalization tank-1 (CET-01). Pipe grid is
provided at bottom of the CET-01 to keep all suspended solids in suspension and to provide proper mixing.
2 nos. of Air Blowers (1W+1 stand-by) shall supply air through to pipe grid.
Then after, equalized wastewater shall be pumped to Neutralization Tank-1 (NT-01) where the continuous
addition and stirring of Caustic solution is done to maintain neutral pH of wastewater from Caustic Dosing
Tanks (CDT-01) as per requirement by gravity. Then after, neutralized wastewater shall go to Flash Mixer-1
(FM-01) by gravity. Alum and Polyelectrolyte shall be dosed from Alum Dosing Tank (ADT-01) and
Polyelectrolyte Dosing Tank (PEDT-01) respectively by gravity into FM-1 to carry out coagulation by using a
Flash Mixer. Then after, coagulated wastewater shall be settled in Primary Clarifier (PCF-01). Treated
effluent will be sent to CETP for further treatment.
SIZE OF TANKS (Stream I)
S.N.
Name of unit
Size (m x m x m)
No
.
MOC/ Remark
1
1
RCC M25+A/A Bk. Lining
Stream I (Low COD & TDS Stream) 22 M3/D
1
Screen Chamber (SC-01)
[0.5x0.5x1 depth]
2
Collection cum Equalization [2.5x2.5x 4 depth]
Tank-1 (CET-01)
3
Neutralization Tank (NT-01)
[2.5x2.5x 4 depth]
1
4
Flash Mixer-1 (FM-01)
1
RCC M25+A/A Bk. Lining
RCC M25
5
Primary Clarifier (PCL-01)
1
RCC M25
0.8 x 0.8 x (1.5 LD +0.5
FB)
[2.5x2.5x 3 Height]
RCC M25+A/A Bk. Lining
RCC M25
PCC
PP
MSEP
SS
=
=
=
=
=
REINFORCED CEMENT CONCRETE (M 25 GRADE)
PLAIN CEMENT CONCRETE
POLYPROPELENE
MILD STEEL EPOXY PAINTED
STAINLESS STEEL
Stream-II: High COD and High TDS effluent (3 KL/Day) will be neutralized and then send to common MEE for
further treatment.
BLOCK DIAGRAM FOR EFFLUENT TREATMENT PLANT (Stream -I)
Screen Chamber
Oil & Grease
Trap
Collection cum
equalization
tank
Neutralization
tank
Primary Settling
tank
CETP
EXPECTED CHARACTERISTIC OF EFFLUENT (STREAM-I)
Sr.
Category of Wastewater
Before Treatment
No.
1
pH
3.5-6.5
After Treatment
6.5-8.0
2
COD (mg/L)
3,200
2,500
3
BOD3 (mg/L)
1,200
800
4
Ammonical Nitrogen (mg/L)
50
30
EXPECTED CHARACTERISTIC OF EFFLUENT (STREAM-II)
Sr.
Category of Wastewater
Before Treatment
No.
1
pH
2-10
2
COD (mg/L)
60,000
3
BOD3 (mg/L)
10,000
4
TDS (mg/L)
60,000
5
Ammonical Nitrogen (mg/L)
500
ANNEXURE: 6
DETAILS OF HAZARDOUS/SOLID WASTE GENERATION, MANAGEMENT AND DISPOSAL
Sr.
Hazardous/Solid Category
Quantity
Mode Of Disposal
No. Waste
MT/Month
Existing
Total after
proposed
expansion
1
Used Oil
5.1
0.2
0.3
Collection, Storage, Transportation
and reuse or sell to Register Reprocessors.
2
Organic Process
28.1
0.06
15
Collection, Storage, Transportation
Waste
and disposal at CHWIF of BEIL,
Ankleshwar or given to cement
industries for co-processing.
3
ETP Sludge
35.3
-10
Collection, Storage, Transportation
and disposal at Common TSDF of
BEIL, Ankleshwar
Discarded
33.1
50
500
Collection, Storage, Transportation
4
Bags & Liners
Nos./Month
Nos./Month
and reuse or sell to GPCB Registered
Discarded
10 Nos./
100
Vendor after Decontamination.
Containers
Month
Nos./Month
5
Process Waste
28.1
-25
Collection, Storage, Transportation
and disposal at CHWIF of BEIL,
Ankleshwar or given to cement
industries for co-processing.
6
Spent Carbon
28.2
-2
Collection, Storage, Transportation
and disposal at CHWIF of BEIL,
Ankleshwar or given to cement
industries for co-processing.
7
Spent Catalyst
28.3
-2
Collection, Storage, Transportation
and give to generator to regenerate
8
Dil. HCl
--100
Collection, Storage, Transportation
and sell to end user
9
Inorganic Salt
--15
Collection, Storage, Transportation
and disposal at Common TSDF of
BEIL, Ankleshwar
ANNEXURE: 7
DETAILS HAZARDOUS CHEMICAL STORAGE FACILITY
Sr.
No.
Name of the
Hazardous
Substance
Maximum
Storage
Mode of
Storage
Actual
Storage
1
Methanol
20 MT
Tank
20 MT x 1
State &
Operating
pressure &
temperature
NTP
Possible type of
Hazards
2
EDC/MDC
20 MT
Tank
20 MT x 1
NTP
3
DMF
10 MT
Tank
20 MT x 1
NTP
4
Toluene
20 MT
Tank
20 MT x 1
NTP
Flammable/
Toxic
Flammable/
Toxic
Flammable/
Toxic
Flammable
5
Acetone
20 MT
Tank
20 MT x 1
NTP
Flammable
6
Ethyl Acetate
20 MT
Tank
20 MT x 1
NTP
Flammable
7
IPA
20 MT
Tank
20 MT x 1
NTP
Flammable
8
HCL
5 MT
Tank
5 MT x 1
NTP
Corrosive
9
H2SO4
5 MT
Tank
5 MT x 1
NTP
Corrosive
ANNEXURE: 8
DETAILS OF FLUE & PROCESS GAS EMISSION AND CONTROL MEASURES
Sr.
No.
Source
Emission
of
Existing
1
Boiler
(Capacity: 0.6 TPH)
2
Process
Vent
(Reactor Vessel)
Stack/Vent
(meter)
Height Diameter
15
0.2
Fuel name &
Quantity use
Type of
Emission
APCE
Natural Gas =
SPM
SO2
NOx
Cl2
NH3
HCl
--
3
300 m /Day
11
0.2
TOTAL AFTER PROPOSED EXPANSION
Flue Gas Emission
1
Boiler (Existing)
15
0.2
(Capacity: 0.6TPH)
--
Natural Gas =
300 m3/Day
SPM
SO2
NOx
SPM
SO2
NOx
SPM
SO2
NOx
Two Stage Water &
Caustic scrubber
--
2
Boiler (Proposed)
(Capacity: 1.0 TPH)
30
0.5
Agro waste = 3
MT/Day
3
Thermic
fluid
heater (Proposed)
(Capacity: 4 Lac K.
Cal/Hr.)
D. G.Set
30
0.5
Agro waste = 2
MT/Day
11
0.1
HSD
SPM
SO2
NOx
--
11
0.2
--
Two Stage Water &
Caustic scrubber
11
0.2
--
Cl2
NH3
HCl
HCl
SO2
4
Process Gas Emission
5
Process
Vent
(Reactor Vessel)
(Existing)
6
Process
Vent
(Reactor Vessel)
(Proposed)
Multicyclone
separator with bag
filter
Multicyclone
separator with bag
filter
Two Stage Water &
Caustic scrubber
ANNEXURE 9
SOCIO - ECONOMIC IMPACTS
1) EMPLOYMENT OPPORTUNITIES
The manpower requirement for the proposed project is expected to generate some permanent
jobs and secondary jobs for the operation and maintenance of plant. This will increase direct /
indirect employment opportunities and ancillary business development to some extent for the
local population. This phase is expected to create a beneficial impact on the local socio-economic
environment.
2) INDUSTRIES
Required raw materials and skilled and unskilled laborers will be utilized maximum from the local
area. The increasing industrial activity will boost the commercial and economical status of the
locality, to some extent.
3) PUBLIC HEALTH
The company regularly examines, inspects and tests its emission from sources to make sure that
the emission is below the permissible limit. Hence, there will not be any significant change in the
status of sanitation and the community health of the area, as sufficient measures have been
taken and proposed under the EMP.
4) TRANSPORTATION AND COMMUNICATION
Since the existing factory is having proper linkage for the transport and communication, the
development of this project will not cause any additional impact.
In brief, as a result of the proposed project there will be no adverse impact on sanitation,
communication and community health, as sufficient measures have been proposed to be taken
under the EMP. The proposed project is not expected to make any significant change in the
existing status of the socio - economic environment of this region.
ANNEXURE – 10
PROPOSED DRAFT TERMS OF REFERENCE
1.
•
•
•
•
•
•
•
•
•
•
Project Description
Justification of project.
Promoters and their back ground
Project site location along with site map of 5 km area and site details providing
industries, surface water bodies, forests etc.
Project cost
Project location and Plant layout.
Water source and utilization including proposed water balance.
Product spectrum (proposed products along with production capacity) and process
List of hazardous chemicals.
Mass balance of each product
Storage and Transportation of raw materials and products.
various
2. Description of the Environment and Baseline Data Collection
• Micrometeorological data for wind speed, direction, temperature, humidity and rainfall in 5 km
area.
• Existing environmental status Vis a Vis air, water, noise, soil in 5 km area from the project site.
For SPM, RSPM, SO2, NOx.
• Ground water quality at 5 locations within 5 km.
• Complete water balance
3. Socio Economic Data
• Existing socio-economic status, land use pattern and infrastructure facilities available in the study
area were surveyed.
4. Impacts Identification And Mitigatory Measures
• Identification of impacting activities from the proposed project during construction and
operational phase.
• Impact on air and mitigation measures including green belt
• Impact on water environment and mitigation measures
• Soil pollution source and mitigation measures
• Noise generation and control.
• Solid waste quantification and disposal.
5.
•
•
•
Environmental Management Plan
Details of pollution control measures
Environment management team
Proposed schedule for environmental monitoring including post project
6.
•
•
•
Risk Assessment
Objectives and methodology of risk assessment
Details on storage facilities
Process safety, transportation, fire fighting systems, safety features and emergency capabilities to
be adopted.
• Identification of hazards
• Consequence analysis through occurrence & evaluation of incidents
• Disaster Management Plan.
7. Information for Control of Fugitive Emissions
8. Post Project Monitoring Plan for Air, Water, Soil and Noise.
9. Information on Rain Water Harvesting
10. Green Belt Development plan
ANNEXURE – 11
GIDC Plot Allotment Letter & GIDC Water Supply Letter
ANNEXURE – 12
Membership Certificate of CETP, ETL-Ankleshwar for disposal of treated effluent
ANNEXURE – 13
Membership Certificate of TSDF & Common Incinerator for disposal of Hazardous waste