global calcium private limited unit...

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PRE-FEASIBILITY REPORT ON ENVIRONMENTAL ASPECTS

PROPOSED EXPANSION

By Addition Of

100 TPA

ACTIVE PHARMACEUTICAL INGREDIENTS (API)

Within Existing Bulk Drug Unit

AT

GLOBAL CALCIUM PRIVATE LIMITED – UNIT III

# 19, 19B, SIPCOT Industrial Complex, Hosur – 635 126.

MARCH 2019

Pre-Feasibility Report GCPL-Unit III

i

CONTENTS

1.0 EXECUTIVE SUMMARY ................................................................................................ 1

2.0 INTRODUCTION ............................................................................................................ 3

3.0 PROPOSED PROJECT ................................................................................................... 3

4.0 PROJECT LOCATION .................................................................................................... 4

5.0 RAW MATERIALS CONSUMPTION .......................................................................... 6

6.0 MANUFACTURING PROCESS .................................................................................. 10

7.0 RAW WATER REQUIREMENT .................................................................................. 58

8.0 ENERGY CONSUMPTION .......................................................................................... 60

9.0 WORK FORCE ............................................................................................................... 60

10.0 EXISTING ENVIRONMENTAL SCENARIO ........................................................... 60

10.1 Air Environment .................................................................................................. 60

10.2 Noise Environment ............................................................................................. 63

10.3 Water Environment ............................................................................................ 63

10.4 Soil Environment ................................................................................................. 66

11.0 WASTE & WASTE MANAGEMENT .......................................................................... 69

11.1 Air Pollution ........................................................................................................... 69

11.2 Wastewater Generation ..................................................................................70

11.3 Solid Wastes ......................................................................................................... 71

12.0 CONCLUSION ............................................................................................................... 71

Pre-Feasibility Report 1 GCPL-Unit III

1.0 EXECUTIVE SUMMARY

1.1 Proposed Project

Global Calcium Private Limited Unit – III has proposed to expand its facility by

installing an additional unit to produce Active Pharmaceutical Ingredient in addition

to existing facility producing mineral salts of Gluconates, Lactates, Lactobionate etc.

1.2 Project Location

The proposed expansion will be carried out within the existing premises of the plant at

19 & 19B, SIPCOT Industrial Complex, Hosur, Krishnagiri District, Tamil Nadu.

1.3 Project Proponent

Global Calcium Private Limited is one of the major producers of Nutrition

Supplements/Additives in the Domestic Market as also in the Global Market. These

Nutrition Supplements are widely used for human consumption as also for veterinary

care.

1.4 Manufacturing Process

Global Calcium Private Limited – Unit III, has proposed to install an API unit within the

existing plant premises.

The existing process of producing Mineral Salts involves neutralization of respective

salts with Gluconic Acid followed by filteration, crystallization, drying and packing.

In the proposed production of Active Pharmaceutical Ingredient (API), the respective

raw material based on the product are hydrolysed in a reactor and then extracted,

centrifuged, and dried.

1.5 Production Capacity

The product at present produced is mineral salts of 1020 TPA (Conversion Process) &

1034 TPA (By Spray Drier Process).

The proposed expansion is to produce 100 TPA of Active Pharmaceutical Ingredients.

1.6 Land Area

The details of Land utilization is as follows

Sl

No Particulars Existing

(in ha.)

Proposed

Addition

(in ha.)

After

Expansion

(in ha.)

1 Built up area 0.273 0.054 0.327

2 Solid waste storage / disposal area 0.237 - 0.237

3 Green Belt / Irrigation area 0.266 - 0.266

4 Road 0.190 - 0.190

5 Vacant area 0.054 - -

Total area 1.02 1.02


1.7 Raw Water Source & Usage

Upon expansion, the total water requirement will be 121.5 KLD. Out of which, 68.7 KLD

through recycling, remaining 52.8 KLD (fresh water requirement) met from SIPCOT

Supply.

1.8 Solid Waste Generation & Method of Disposal

The quantity of solid waste generation and disposal methods for existing and proposed

expansion are given in the following table.

Sl.

No.

Type of Solid Waste Quantity

TPA

Disposal/Treatment

Existing

1. Spent catalyst / spent carbon 2.0 Stored in HDPE Bags used for

Common Landfill-TSDF

2. Chemical sludge from waste

water treatment

0.5 Stored in HDPE Bags used for


3. Used/spent oil 0.2 Recover and Reuse-CPCB Authorized

recyclers

Proposed Expansion

1. Ash from Boiler 200 Sold to brick manufactures


water treatment plant


Common Landfill

3. Concentration or evaporation

residues

105 Stored in HDPE Bags used for

Common Landfill

4. Process Residue and wastes 145 Stored in HDPE Bags used for

Common Landfill

5. Spent Solvent 30 Authorized recyclers

1.9 Man Power Requirement

The existing work force of 70 Nos. additional man power requirement will be 80 Nos.

Upon expansion the total work force will be 150 Nos.

1.10 Estimated Project Cost

The total project cost for the proposed expansion is ` 10 Crores.

1.11 Pollution Control Cost

The total pollution control cost for proposed plant is ` 2.5 Crores.


2.0 INTRODUCTION

As an EU-GMP certified global company and an established hallmark for pharmaceutical

standards, Global Calcium has stood the test of time since its inception in 1979 as

Calcium India. Today, Global Calcium represents the true hallmark of quality when it

comes to pharmaceutical products.

Global Calcium is backed by an excellent management team comprising of industry

specialists, technocrats, entrepreneurs and business specialists bringing in strong

domain expertise in the pharmaceutical industry.

Global Calcium prioritizes Research and Development over everything else; companies

today are well aware that only with superior R & D can they continue to innovate and

deliver international-quality products. The focused R&D effort and initiatives are behind

the cost advantages that the end customers enjoy.

Global Calcium's goal is to develop genuine business partnership with clients to result

in a win-win strategy. By combining its resources and expertise with its strategy

pattern Global Calcium achieves product development objectives and successful

completion of quality health formulations and products.

Global Calcium is one of the major producers of Nutrition Supplements/Additives in the

Domestic Market as also in the Global Market. These Nutrition Supplements are widely

used for human consumption as also for veterinary care.

3.0 PROPOSED PROJECT

Global Calcium Private Limited Unit – III has proposed to expand its facility by

installing an additional unit to produce Active Pharmaceutical Ingredient in addition

to existing facility producing mineral salts of Gluconates, Lactates, Lactobionate etc.

The proposed expansion will be carried out within the existing premises of the existing

plant site itself.


The production details at present are as follows.

Processing in the Plant

by Conventional Process Pharmaceutical bulk drugs and

chemicals such as

Mineral salts of Gluconates, Citrates, Lactates, Lactobionates,

Fumarates, Orotates, Ascorbates, Aspartates, Pidolates, Bis

Glycinate, Calcium D Saccharate, Pyrophosphates, etc

1020

by spray drier process

Calcium Glubionate , Calcium Borogluconate, Calcium lacto

Gluconate, Gluconates, Aspartates, Pidolates and other Mineral

Salts

1034

It is now proposed to expand by additionally installing a unit to produce Active

Pharma Ingredients (API) Products.

API Products (Active Pharma Ingredients) such as

Iron sucrose, Calcium dobesylate, Tiemonium methyl sulphate,

Ethamsylate, Tolperisone Hcl, Glycerophosphates, Fenspride

Hydro Chloride, Clozapine, Nifuroxide, Oxetacaine, Benfotiamine,

Calcium folinate, Trimetazidine Hydro chloride, Calcium methyl

Folate, Ubiquinol Acetate, Strontium ranelate, Phenyramidol

Hydrochloride, Iron Sorbitol Complex, , Naftifine Hydrochloride,

Esmolol Hydrochloride, L- Methyl Folate, Minoxidil, Mebeverine

Hydrochloride, Terbinafine etc

100

4.0 PROJECT LOCATION

The proposed expansion is within the premises of the existing plant site located at #

19, 19B SIPCOT Industrial Complex, Hosur – 635 126, Tamil Nadu, which is a notified

industrial estate in Tamil Nadu.

State Industries Promotion Corporation of Tamil Nadu (SIPCOT) Limited, a fully

government owned premier institution, established in the year 1972, has been a

catalyst in development of small, medium and large scale industries in Tamil Nadu.

Total Area of the SIPCOT Complex Phase-1 at Hosur is 1235.86 Acres, which is well

connected by National Highway (NH-7) ie Chennai - Bangalore Highway. SIPCOT has

also established all requisite infrastructure to supply water to all the industries, and

have also established an exclusive substation to ensure uninterrupted power supply.

The Location Map is as shown in Fig.1.0.


Fig 1.0 LOCATION MAP


5.0 RAW MATERIALS CONSUMPTION

Existing List of Raw Materials including chemicals, Catalysts & Additives

S.

No Description Total (T/Year)

1 Dextrose Mono Hydrate 500

3 Gluconic acid/Glucono Delta Lactone 2000

4 Potassium (Bi)Carbonate 12

5 Calcium Carbonate 344

6 Sodium (Bi) carbonate 42

7 Zinc Carbonate/ Zinc Oxide 18

8 Magnesium Carbonate/Oxide 100

9 Manganese Carbonate/ Oxide 6

10 Lactic acid 250

11 Calcium Gluconate 60

12 Calcium Lactobionate 15

13 Calcium Lactate 72

14 Denatured Spirit 220

15 Lactose 100

16 Boric acid 2

18 Ferrous Sulphate/Iron Powder 50

19 Orotic acid 48

20 Citric acid 400

21 Pyro Glutamic acid 15

22 L- Aspartic acid 15

23 Ascorbic acid 30

24 Glycine 10

25 Nitric acid 50

26 Calcium Nitrate 25

27 Hydrogen Per oxide 10

28 Sulphuric acid 6

29 Tri Sodium Pyro Phosphate 30


Proposed List of Raw Material

Sl. No. Raw Material kgs/ Annum State

1 Ferric Chloride 4100 Solid

2 Sodium Carbonate 320 Solid

3 Sucrose 16000 Solid

4 Hydroquinone 7400 Solid

5 Sulphuric Acid 9500 liquid

6 Calcium carbonate 4800 Solid

7 Marpholine 5000 liquid

8 2-Acetyl Thiophene 4800 liquid

9 HCl 16800 liquid

10 Phenyl Magnesium bromide 1500 liquid

11 P-Formaldehyde 3000 liquid

12 Dimethyl Sulphate 500 Solid

13 Diethylamine 1200 liquid

14 4-Methylpropiophenone 2000 liquid

15 Piperidine 1700 liquid

16 1,3 dioxolone 3000 liquid

17 Epichlorohydrin 4200 liquid

18 Trisodium phasphate 11000 Solid

19 Calcium Chloride 3300 Solid

20 Magnesium Chloride 1000 Solid

21 Thiamine HCl 15000 liquid

22 Orthophophoric acid 15000 liquid

23 P2O5 15000 liquid

24 Sodium Hydroxide 21000 Solid

25 Benzoyl Chloride 9000 liquid

26 Folic acid 2000 Solid

27 Triethylamine 2000 liquid

28 citric acid 2300 liquid

29 chlorosulphonicacid 800 liquid

30 methylne dichloride 800 liquid

31 morpholine 400 Solid

32 suphur 200 Solid

33 potassium carbonate 200 Solid

34 methylbromoacetate 400 liquid

35 strontium hydroxide 200 Solid

36 malano nitrile 200 liquid

37 Nitromethane 3600 liquid

38 DMSO 2400 liquid

39 Pottasium carbonate 1800 Solid

40 Zinc dust 1500 Solid

41 Ammonia 800 liquid

42 Sorbital 2000.0 liquid

43 Dextrin 1500.0 Solid

44 N-Methyl -naphthyl methanamine 1600.0 liquid

45 Sodium bicarbonate 800.0 Solid


46 Cannamyl chloride 600.0 Solid

47 Activated carbon 5000 Solid

48 Hyflo 5000 Solid

49 Nitrofurfural diactate 5400 Solid

50 Hydroxy benzohydrazide 4500 Solid

51 Dimethyl benzyl carbinol 500 Liquid

52 Dimethyl sulphate 300 Solid

53 Pottasium hydroxide 500 Solid

54 PEG-400 100 Liquid

55 Chloroacetyl chloride 200 Solid

56 2-Aminopyridine 2400 Liquid

57 Lithium 1550 Solid

58 styrene oxide 1500 Solid

59 IPA-HCl 2000 Liquid

60 2,3,4- trimethoxy benzaldehyde 3000 Liquid

61 Piperazine 1250 Liquid

62 5% palladium on carbon 1500 Solid

63 Isoproponolic acid 1800 Liquid

64 Coenzyme-Q10 1200 Solid

65 Acetic anhydride 1640 Liquid

66 N-heptane 200 Liquid

67 4-Hydroxy benzaldehyde 600 Liquid

68 pyridine 250 Liquid

69 malonic acid 300 Solid

70 hydrogen gas 200 Gas

71 Dimethyl formamide 200 Liquid

72 Isopropalamine 300 Liquid

73 Folic acid 1200 Solid

74 sodium borohydride 600 Solid

75 formaldehyde 400 Liquid

76 S-Phenylethyl amine 140 Liquid

77 Hydrogen peroxide 5200 Liquid

78 urea 4550 Solid

79 phthalic anhydride 3900 Liquid

80 2,4 diamino-6- chloropyrimidine 2600 Liquid

81 piperdine 1300 Liquid

82 Veratric acid 3000 Liquid

83 1,4 Dibromobutane 2000 Liquid

84 Potassium hydroxide 1500 Solid

85 1-2-ethylaminopropane 2000 Liquid

86 Methylisobutyl ketone 1000 Liquid

87 potassium carbonate 1000 Solid

Total RM quantity 274000 274 MT


Proposed List of Raw Material – Solvents

Sl. No. Total qty of solvent Lts/ annum Storage

1 Toluene 45000 U/G

2 DMF 6000 Barrel

3 Acetone 46000 U/G

4 Hexane 12000 Barrel

5 DNS 300000 U/G

6 Methanol 800000 U/G

7 THF 12000 Barrel

8 Pyridine 8000 Barrel

9 MTBE 16000 Barrel

10 EDC 31000 U/G

11 MDC 34000 Barrel

12 Isopropanol 16000 Barrel

13 Ethyl Acetate 21000 U/G

Total 1347000


6.0 MANUFACTURING PROCESS

Existing

Calcium Gluconate

Gluconic Acid procured from market is neutralized with Calcium carbonate, filtered,

crystallised, centrifuged, dried, milled and packed.

Alternate process for the manufacture of Calcium Gluconate

Gluconic acid is neutralised with Calcium carbonate, filtered, crystallised, centrifuged,

dried, milled and packed.

Alternate process

NEUTRALISATION FILTERATION

CRYSTALLISATION

PACKING MILLING DRYING CENTRIFUGING

NEUTRALISATION FILTRATION CRYSTALLISATION


GLUCONO DELTA LACTONE + CaCO3 + WATER

(NEUTRALISATION) FILTRATION CRYSTALLISATION



Sodium Gluconate

Gluconic acid brought from the market is neutralised with Sodium bi-carbonate,

filtered, concentrated, crystallised, centrifuged, dried, milled and packed.

Alternate process for the manufacture of Sodium Gluconate

Gluconic acid is neutralised with Sodium carbonate / Sodium Bicarbonate, filtered,

concentrated, crystallised, centrifuged, dried, milled and packed.

Alternate process



CONCENTRATION

NEUTRALISATION FILTRATION

CRYSTALLISATION


CONCENTRATION

GLUCONIC ACID + SODIUM

CARBONATE / BICARONATE

(NEUTRALISATION) FILTRATION SIEVING

PACKING

DRYING


Potassium Gluconate

Gluconic acid brought from the market is neutralised with Potassium carbonate,


Alternate process for the manufacture of Potassium Gluconate

Gluconic acid is neutralised with Potassium carbonate / Potassium Bicarbonate,


Alternate process



CONCENTRATION


CRYSTALLISATION


CONCENTRATION

GLUCONIC ACID +

POTASSIUM CARBONATE /

BICARONATE

(NEUTRALISATION)

FILTRATION SIEVING

PACKING

DRYING


Magnesium Gluconate

Gluconic acid brought from the market is neutralised with Magnesium carbonate,


Alternate process for the manufacture of Magnesium Gluconate

Gluconic acid is neutralised with Magnesium carbonate, filtered, concentrated,


Alternate process



CONCENTRATION


CRYSTALLISATION


CONCENTRATION

GLUCONIC ACID +

MAGNESIUM CARBONATE


PACKING

DRYING


Zinc Gluconate

Gluconic acid brought from the market is neutralised with Zinc carbonate/Zinc Oxide,


Alternate process for the manufacture of Zinc Gluconate

Gluconic acid is neutralised with Zinc carbonate/Zinc Oxide, filtered, concentrated,


Alternate process



CONCENTRATION


CRYSTALLISATION


CONCENTRATION

GLUCONIC ACID + ZINC

CARBONATE / ZINC OXIDE


PACKING

DRYING


Manganese Gluconate

Gluconic acid brought from the market is neutralised with Manganese carbonate/

Manganese Oxide, filtered, concentrated, crystallised, centrifuged, dried, milled and

packed.

Alternate process for the manufacture of Manganese Gluconate

Gluconic acid is neutralised with Manganese carbonate/ Manganese Oxide, filtered,

concentrated, crystallised, centrifuged, dried, milled and packed.

Alternate process



CONCENTRATION


CRYSTALLISATION


CONCENTRATION

GLUCONIC ACID +

MANGANESE CARBONATE /

MANGANESE OXIDE

(NEUTRALISATION)

FILTRATION SIEVING

PACKING

DRYING


Calcium Lactate

Lactic Acid is neutralised with Calcium carbonate, filtered, crystallised, centrifuged,

dried, milled and packed.

Calcium Glubionate

In this process, calculated quantities of both Calcium Gluconate and Calcium

Lactobionate are charged in the blender and mixed, sieved and packed.

Alternate Process for the manufacture of Calcium Glubionate

Calculated quantities of Calcium Gluconate and Calcium Lactobionate are mixed in DM

water, filtered, dried, sieved and packed.



BLENDING SIEVING PACKING

MIXING SIEVING PACKING FILTERING DRYING


Calcium Lacto Gluconate

In this process, calculated quantities of Calcium Lactate and Calcium Gluconate are

charged in the blender and mixed, sieved and packed.

2. Alternate Process for the manufacture of Calcium Lacto Gluconate

Calculated quantities of Calcium Lactate and Calcium Gluconate are mixed in DM water,

filtered, dried, sieved and packed.


Calculated quantities of Gluconic Acid, Lactic Acid are reacted with calcium carbonate,

filtered, dried, sieved and packed.


MIXING SIEVING PACKING FILTERING DRYING

BLENDING SIEVING PACKING

GLUCONIC ACID + LACTIC

ACID + CaCO3


PACKING

DRYING

GLUCONO DELTA LACTONE +

LACTIC ACID + CaCO3


PACKING

DRYING


Calcium Lactobionate

Calculated quantities of Lactose, Sodium bromide, Calcium Carbonate are mixed in

water, electrolysed, filtered, vaccum concentrated, crystallised with alcohol,

centrifuged, milled, dried and packed in bags/ Fibre drums.

ELECTROLYSIS FILTRATION

CRYSTALLISATION


VACCUM

CONCENTRATION

LACTOSE,

SODIUM BROMIDE,

CALCIUM CARBONATE,

DM WATER


Calcium Borogluconate :

1. Calculated quantities of calcium gluconate and Boric acid are charged in the

blender and mixed sieved & packed.

2. Alternate Process

Calculated quantities of calcium gluconate & Boric acid dissolved in DM Water, filtered,

spray dried, sieved & packed.

Ferrous Gluconate :

BLENDING

SIEVING PACKING

CALCIUM

GLUCONATE + BORIC

ACID + DISSOLVED IN

DM WATER

FILTERED DRIED

PACKED SIEVED

CALCIUM

GLUCONATE +

FERROUS SULPHATE

+ DM WATER

FILTERATION CONCENTRATION

PACKING MILLING DRYING


Manufacturing Process

Proposed

1 IRON SUCROSE

Ferric Chloride is dissolved in water and sodium bicarbonate solution is added to

precipitate ferric hydroxide which is filtered.

Above ferric hydroxide is mixed with sucrose and heated to get iron sucrose in solution.

Which is concentrated to get thick mass which is added with vigorous stirring to DNS

and then methanol to precipitate iron sucrose solid. This is centrifuged and slurried with

DNS and acetone again to remove the impurities. The wet material is dried under

vacuum, pulverized, redried, milled, blended as needed and packed.

Raw material:

Ferric Chloride

Sodium carbonate

Sucrose

DNS denatured spirit

Methanol

Acetone

Raw material consumption per kg of output

Ferric Chloride = 0.2 kg / kg

Sodium Carbonate = 0.04 kg / kg

Sucrose = 2 kg / kg

DNS = 8 L / kg

Methanol = 5 L / kg

Acetone = 1 L / kg


PROCESS FLOW CHART

Sodium carbonate

solution

MLR collection

Heat

DNS

MLR collection

methanol

DNS

Acetone MLR collection

Water + Ferric Chloride

Filtration of Ferric hydroxide

Ferric hydroxide Cake + Sugar

Concentrated

Filtration

Filter Mass

Filtration

Vacuum Drying

Milling, Blending & Packing


2. CALCIUM DOBESYLATE

Stage-I: Sulphuric acid is added to a suspention of hydroquinone in ethylene di

chloride. After the sulfonation, water is added and aqueous layer separated.

Stage-II: aqueous layer is neutralized with a slurry of calcium carbonate in water,

centrifuged to separate calcium sulfate.

Liquid from centrifuge is concentrated, chilled, the product filtered and washed with

isopropanol and dried.

Raw material:

Hydroquinone

Sulphuric acid

Calcium carbonate

Ethylene di chloride

Isopropanol


Hydroquinone = 1.2 kg

Sulphuric acid = 1.6 kg

Calcium carbonate = 1.6kg/kg

Ethylene di chloride = 4L/kg

Isopropanol = 2L/kg


PROCESS FLOW CHART

Stage-1

sulphuric acid

layer separation

Stage-II

calcium carbonate

centrifuge

concentrated

chilled

isopropanol

Hydroquinone + ethylene di chloride

Aqueous layer

Liquid from centrifuge

Crystallisation

Drying

Centrifugation


Residue


3. TIEMMONIUM METHYL SULPFATE (TMS)

Morpholine is reacted with 2-acetyl thiophene and p-formaldehyde in the presence of

hydrochloric acid in denatured spirit (DNS) to get the corresponding mannich base as

HCl salt. The above HCl salt is basified in toluene to get the corresponding mannich

ketone base. This is reacted with phenyl magnesium bromide in tetrahydrofuran to get

tiemmonium hydrochloride which is purified using methanol slurry. The pure

hydrochloride is converted to base and treated with dimethyl sulfate in acetone to get

the tiemmonium methyl sulfate. This is dried in a vacuum oven, milled, blended and

packed.

Raw material:

Morpholine

2- Acetyl thiophene

P-Formaldehyde

Hydrochloric acid

Denatured spirit (DNS)

Phenyl magnesium bromide

Dimethyl Sulfate

Tetrahydrofuran

Methanol

Toluene

acetone


Morpholine = 1 kg / kg

2- Acetyl thiophene = 1.5 kg / kg

P-Formaldehyde =0.7 kg / kg

Hydrochloric acid = 5.7 kg / kg

Denatured spirit (DNS) = 6L / kg

Phenyl magnesium bromide =2.3 kg / kg

Dimethyl Sulfate =0.5 kg / kg

Methanol = 3L/kg

Tetrahydrofuran = 2L/kg

Toluene = 8 L/kg

Acetone = 5L/kg


PROCESS FLOW CHART

Con. HCl

Reflux

MLR collection

Phenyl magnesium bromide

Con. HCl

Methanol MLR collection

Dimethy sulphate

MLR collection

Morpholine + 2- Acetyl thiophene +

P-Formaldehyde +DNS

Cool, Centrifugation, Basification

Ketone Base

Quenching ice water

Centrifugation

Basification with Ammonia

Centrifugation

Vacuum Drying



4 ETHAMSYLATE

Stage-I: Sulphuric acid is added to a suspention of hydroquinone in ethylene di

chloride. After the sulfonation, water is added and aqueous layer separated.

Stage-II: aqueous layer is neutralized with diethylamine, concentrated, chilled, the

product filtered and washed with isopropanol and dried.

Raw material:

Hydroquinone

Sulphuric acid

Diethylamine

Ethylene di chloride

Isopropanol


Hydroquinone =0.8 kg/kg

Sulphuric acid = 1.5 kg/kg

Diethylamine = 1.6 L/kg

Ethylene di chloride = 2.3L/kg

Isopropanol = 0.5L/kg


PROCESS FLOW CHART

Stage-I:

Suphuric acid

water

layer separation

stage-II

diethylamine

concentration

isopropanol

hydroquinone + ethylene di chloride

Sulphonated mass

Aqueous layer

Crystallisation

Drying

Centrifugation


Chill, residue


5 TOLPERISONE HCl

Mixture of 4-methyl propiophenone, piperidine, and hydrochloric acid heated to reflux

in 1,3-dioxalone. After the reaction is over, diluted with ethyl acetate and chilled with

stirring. Product formed is centrifuged, washed with ethyl acetate. The crude product

is purified with methanol and ethyl acetate using charcoal.

Raw material:

1.4-methyl propiophenone

2. piperidine

3.1,3-dioxalone

4. conc. hydrochloric acid

5. ethyl acetate

6. methanol


1.4-methyl propiophenone 1.0 kg

2. piperidine 0.6 kg

3.1,3-dioxalone 1.5 kg

4. conc.hydrochloric acid 0.025 L

5. ethyl acetate 3.0 L

6. methanol 1.0 L


PROCESS FLOW CHART

Reflux

chill

stage-1

charcoal

filter

4-methyl propiophenone+piperidine+

HCl + 1,3-dioxolane

Dilute with ethyl actate

Centrifugation

Dissolve stage-1 in methanol

centrifugation

Filtrate , concentrate, add ethyl

acetate, chill

Vacuum drying



6. a. CALCIUM GLYCEROPHOSPHATE

Stage – I: Epichlorohydrin is hydrolised with dilute acid, and reacted with Tri sodium

phosphate, to get Crude sodium Glycerophosphate.

Stage –II : To the Above crude Sodium Glycerophosphate solution , Calcium chloride is

added to get Crude Calcium Glycerophosphate

Stage – III : crude Calcium Glycerophosphate is washed with DNS: Water mixture to

get Pure Calcium Glycerophosphate, which is centrifuged and dried.

Raw material:

1. Epichlorohydrin

2. Trisodium phosphate

3. Calcium chloride

4. Denatured spirit (DNS)


1. Epichlorohydrin = 1.5 kg / kg

2. Trisodium phosphate = 6.0 kg / kg

3. Calcium chloride = 2.0 kg / kg

4. Denatured spirit (DNS) = 5.0 L / kg


PROCESS FLOW CHART

Stage - I

Reflux

Hot condition

Stage -II

Calcium chloride

Stage -III

DNS: Water

Epichlorohydrin + water

Reaction with Trisodium phosphate

Charcoal treatment & Filtration

Reaction with calcium chloride

Drying

Centrifugation & Slurry wash



6.b. MAGNESIUM GLYCEROPHOSPHATE


phosphate, to get Crude sodium Glycerophosphate.

Stage –II : To the Above crude Sodium Glycerophosphate solution ,Magnesium

chloride is added to get Crude Magnesium Glycerophosphate

Stage – III : crude Magnesium Glycerophosphate is washed with DNS: Water mixture

to get Pure Magnesium Glycerophosphate, which is centrifuged and dried

.

Raw material:

4. Epichlorohydrin


6. Magnesium chloride



8. Epichlorohydrin =1.5 kg / kg

9. Trisodium phosphate = 6 kg / kg

10. Magnesium chloride = 3 kg / kg

11. Denatured spirit (DNS) = 5L / kg


PROCESS FLOW CHART

Stage - I

Reflux

Hot condition

Stage -II

Magnesium chloride

Stage -IV

DNS: Water




Reaction with Magnesium chloride

Drying



Concentration


6. c. SODIUM GLYCEROPHOSPHATE


phosphate, to get Crude sodium Glycerophosphate solution which is concentrated and

filtered to get Crude sodium Glycerophosphate

Stage – II : crude Sodium Glycerophosphate is washed with DNS: Water mixture to

get Pure Sodium Glycerophosphate, which is entrifuged and dried

.

Raw material:

1. Epichlorohydrin




4. Epichlorohydrin =1 kg / kg

5. Trisodium phosphate = 6 kg / kg

6. Denatured spirit (DNS) =5L / kg


PROCESS FLOW CHART

Stage - I

Reflux

Hot condition

DNS

Stage -II

DNS: Water




Crystallisation

Drying



Concentration


7 FENSPIRIDE HYDROCHLORIDE

MANUFACTURING FLOWCHART:

Stage-1:

1-(2-phenylethyl)-4-piperidone

Hydrochloric acid

Water, centrifuge, dry

Stage-II : Fenspiride Hydrochloride Crude

Zinc Dust

basify with Aq. ammonia

Dichloromethane

Concentration

Toluene, Diethyl carbonate

water, toluene

acidify, Hydrochloric

acid

cool, centrifuge, dry

Stage-III: Purification

Stage-II

Heat

Acetone

Cool & Centrifuge,

Nitromethane+ DMSO +

Potassium Carbonate, 0 deg.C

Stage-1

Methanol + Stage-1+

Hydrochloric acid, <5 deg.C

Dichloromethane layer

toluene layer

Stage-II

Methanol

Concentrate

Drying, milling, Sieving+ packing

Residue


Manufacturing process for the Fenspiride Hydrochloride:

Stage-I: 4-(nitromethyl)-1-phenethylpiperidin-4-ol is prepared by reacting 1-(2-

phenylethyl)-4-piperidone with nitromethane and potassium carbonate in

dimethylsulfoxide. stage-1 is isolated by quenching in water Centrifuging.

Stage-II: Fenspiride hydrochloride crude is prepared by the reduction of stage-I with

zinc dust and hydrochloric acid, basification with aqueous ammonia and extracting with

dichloromethane. Dichloromethane extract is concentrated to get 4-(aminoethyl)-1-

phenylpiperidin-4-ol, which is reacted with diethylcarbonate in the presence of sodium

methoxide to get Fenspiride base. This is treated with Hydrochloric acid to get

Fenspiride hydrochloride crude.

Stage-III: Fenspiride HCl crude dissolved in methanol , treated with Activated carbon.

filtered, filtrate concentrated completely, Acetone is added , solid centrifuged, dried

under vacuo <60 deg.C , milled ,sieved and packed.

8 CLOZAPINE :

MANUFACTURING FLOW CHART

2-chloro benzoic acid

reduction

water +sodium dithionate

stage-1

cyclisation, xylene

stage-2

N-methylpiperazine, TiCl4

stage-3

recrystallisation

4-chloro-2-nitro aniline

+potassium carbonate +DMF

2-( 4-chloro -2-amino diphenylamino)benzoic

acid

8-chloro-5H-benzo-[b,e][1,4]diazepine-11-

10H-one

crude clozapine

pure clozapine

Drying, sieving and packing


Brief process description:

Stage-1:

4-chloro-2-nitro aniline is reacted with 2-chloro bezoic acid and th e resulting product

is reduced in-situ with sodium dithionate in water to get 2-( 4-chloro -2-amino

diphenylamino)benzoic acid stage-1

Stage-2:

Stage-1 is cylised in refluxing xylene to get 8-chloro-5H-benzo-

[b,e][1,4]diazepine-11-10H-one

Stage-3:

Stage-2 is reacted with N-methyl piperazine in presence of titanium tetrachloride to

get crude clozapine (stage-3)

Stage-4: pure clozapine

Crude clozapine is purified to pure clozapine by dissolving in methanol , charcolising,

filtering, concentrating and cooling. The product is centrifuged, dried under vacuum

below 60 deg.C , milled , sieved and packed.

9 NIFUROXAZIDE

MANUFACTURING FLOW CHART:

Synthesis of Nifuroxazide:

Nitrofurfural diacetate

Heat

4-hydroxy benzohydrazide

Hydrochloric acid

Heat & Cool

Centrifuge

Methanol

Centrifuge

Manufacturing procedure for Nifuroxazide:

Nitrofufural Diacetate reacts with 4-hydroxy benzohydrazide in the presence of sulfuric acid

in DNS to form the Nifuroxazide.

Water +Sulphuric acid+ DNS

Reaction mass

Reaction mass

Wet cake, reflux

Drying, milling, sieving, packing


10 OXETACAINE MANUFACTURING FLOW CHART:

Stage-I:

Sulfuric acid

water

Centrifuge, dry

Stage-II: Methylation

Dimethyl sulfate

Potassium hydroxide

Heating

Water

Extraction & Distillation

Stage-III:

PEG-400

heating Sodium Hydroxide

dichloro ethane

Water

Extraction

Layer separation

Chloroacetyl chloride

Sodium hydroxide

Extraction & Distillation

Dimethyl benzyl carbinol +

Acetonitrile

Stage-I+ Toluene

Dimet

stage-1

Reaction Mass

Residue

Stage-II

Reaction Mass

Organic layer

Residue


Stage-IV: Oxetacaine crude

Etanol amine Toluene

Sodium Hydroxide

Heating

Water

Extraction , layer separation

Hydrochloric acid

Extraction, layer separation

Ammonia

Centrifuge, dry

Stage-V: Purification

Isopropyl alcohol

Water

Centrifuge

Manufacturing Process of Oxetacaine:

Stage-1: Dimethyl benzyl carbinol is reacted acetonitrile and sulfuric acid to get

stage-I.

Stage-I1: Stage-I methylated with dimethyl sulfate in the presence of potassium

hydroxide in toluene to stage-II.

Stage-II1: Stage-II hydrolyzed with sodium hydroxide and reacted with chloroacetyl

chloride to stage-III.

Stage-IV: Stage-III reacted with ethanol amine in the presence of sodium hydroxide

in toluene to stage-IV (Oxetacaine crude).

Stage-V: Oxetacine crude crude purified using Isopropyl alcohol and water to get

pure Oxetacaine

11 BENFOTIAMINE

Mixture of thiamine HCl and orthophosphoric acid is heated and phosphorous pentoxide

is added slowly over a period. Diluted by adding water and Hydrolysed by heating to

reflux

The above solution is basified with sodium hydroxide and treated with benzoyl chloride

in methylene di chloride at low temperature. After the reaction, centrifuged to remove

inorganics, the MLR is concentrated and filtered. The filtrate is acidified to get the

crude benfotiamine which is centrifuged and washed with water.

crude product is dissolved in dilute sodium hydroxide, charcolised, filtered, acidified to

get the pure product which is centrifuged, washed with water, methanol and spin dried.

Residue

Reaction

Organic layer

Acidic layer

stage-IV

Stage-IV



The wet material is dried under vacuum, pulverized, milled, blended as needed and

packed.

Raw material:

1. thiamine HCl

2.orthophosphoric acid

3.phosphorous pentoxide

4.Sodium hydroxide

5.benzoyl chloride

6.Hydrochloric acid

7.methylene chloride

8.methanol


1. thiamine HCl 2.5 kg

2.orthophosphoric acid 3.5 kg

3.phosphorous pentoxide 2.5 kg

4.Sodium hydroxide 2.5 kg

5.benzoyl chloride 1.5 kg

6.Hydrochloric acid 2.5 L

7.methylene chloride 5.0 L

8.methanol 2.0 L

PROCESS FLOW CHART

Phosphorous pentoxide

heat

water

reflux, cool

benzoyl chloride

in DCM

hydrochloric acid

Hydrochloric acid

Thiamine HCl + orthophosphoric

acid

Reaction mixture

Reaction mixture+ sodium

hydroxide

Centrifugation

Above solid + aq. sodium hydroxide

Charcoalise, filter

Centrifuge, MLR concentrate


12 CALCIUM FOLINATE

Folic acid dissolved in water and treated with sodium borohydride under cooling. The

mixture is quenched into hydrochloric acid and then formylated using formic acid. The

reaction solution is concentrated under vacuum and centrifuged to get stage-1(formyl

folic acid). Stage-1 is reacted with triethylamine in water and then converted to the

corresponding calcium salt using calcium chloride. The product is precipitated by adding

DNS. The crude product is purified using water and DNS. Washed with acetone and

dried. The wet product is dried under vacuum, milled and sieved and packed.

Raw material:

1. folic acid

2. sodium borohydride

3. conc. HCl

4. triethyl amine

5. calcium chloride

6. DNS

7.acetone

8.formic acid

9. Methanol


1. folic acid 2.5 kg

2. sodium borohydride 5 kg

3. conc. HCl 7 L

4. triethyl amine 2 L

5. calcium chloride 2 kg

6. DNS 75 L

7.acetone 5 L

8.formic acid 70 L

9. methanol 5L

PROCESS FLOW CHART

Sodium boro hydride

Centrifugation


Vacuum drying

Folic acid in water


Formic acid

Stage -1

triethylamine

DNS

calcium chloride

Quench into HCl

Filtration, concentration

Centrifugation

Stage-1 in water

Drying under vacuum

Milling, sieving Blending & Packing

Reaction mixture

centrifugation

recrystallisation

centrifugation


13. TRIMETAZIDINE HYDROCHLORIDE

Stage-I: Synthesis of Trimetazidine Hydrochloride crude

Piperazine

5% Palladium on

Carbon

Hydrogenator

Centrifuge, Concentrate

Toluene,water


isopropanolic HCl,cool

Centrifuge, dry

Stage-II: Purification of Trimetazidine crude

Methanol

activated carbon

heat, filter

concentrate

Acetone

Centrifuge

Manufacturing procedure for Trimetazidine Hydrochloride:

Stage-I: 2,3,4-trimethoxy benzaldehyde and piperazine is condensed and reduced

using Palladium on carbon and Hydrogen gas and isolated as , trimetazedine

hydrochloride crude

Stage-II: Stage-I purified by dissolving in methanol, charcolisation, filtration,

concentration. pure Trimetazidine hydrochloride. is isolated by adding acetone.

2,3,4-trimethoxy

benzaldehyde

+ Methanol

Reaction mass

Residue

Toluene Layer

Stage-I

Stage-I

filtrate

Residue

Drying, Milling, Sieving,

packing


14 CALCIUM METHYLFOLATE


Stage-I: Synthesis of Calcium Methylfolate crude

Sodium Hydroxide

sodium borohydride

acidification, centrifugation

Sodium Borohydride

Formaldehyde

acidification, centrifugation

Calcium chloride

Centrifuging ,drying

Stage-II: Purification of Calcium methylfolate:

Water

hydrochloric acid,

Centrifuge

Sodium hydroxide

Calcium chloride

calcium chloride

Centrifuge

Manufacturing process for Calcium methylfolate:

Stage-I: A solution of Folic acid in sodium hydroxide is reduced with Sodium

borohydride to get tetrahydrofolate, which is reacted with formaldehyde and reduced

again with sodium borohydride and then treated with calcium chloride to get Calcium

methylfolate crude.

Stage-II: methyl folic acid is precipitated by acidification of the crude product

which is redissolved in Sodium hydroxide, charcoalised, filtered and reprecipitated

as pure calcium methyl folate by adding filtered calcium chloride solution.

Stage-I

solid +water

Process water+ Folic acid

Centrifugate


Centrifugate

crude CaMeF


15 UBIQUINOL ACETATE


Pyridine , Zinc Dust

Acetic Anhydride

Cooling, acidification,

n-heptane, layer separation

concentration

DNS

Centrifuge

Manufacturing Procedure of Ubiquinol acetate:

Coenyme Q10 reduced with Zinc dust in the presence of Hydrochloric acid, reacted

with acetic anhydride to get Ubiquinol acetate, which is extracted with n-heptane and

isolated by addition of DNS.

16. STRONTIUM RANELATE

Stage-I: ethyl acetone dicarboxilate is made by reacting citric acid with chlorosulfonic

acid in methylene chloride

Stage – II: ethyl acetone dicarboxilate is condensed with , Malano nitrile and Sulphur

in presence of triethylamine to get stage-II

Stage –III: Stage –II is reacted with Methyl bromoacetate and Potassium carbonate

in Acetone, and to get alkylated Stage –II.

Stage –IV; Stage –III reacted with strontium hydroxide in water under reflux condition

to get the final product which is washed with water, dried, milled and packed.

Raw material:

Triethylamine/Morpholine,

Methanol,

Malano nitrile

Sulphur

Acetone,

Potassium carbonate and

Methyl bromoacetate

Strontium hydroxide

isopropanol

Coenzyme Q10

n- heptane layer

residue

Drying, Milling, sieving, Packing



Citric acid = 2 kg / kg

Chlorosulphonic acid = 2kg / kg

Methylene dichloride =2 L / kg

Morpholine = 1.8 kg / kg

Methanol = 8 L / kg

Malano nitrile = 0.6 kg / kg

Isopropanol = 2L/kg

Suphur = 0.2 kg / kg

Acetone = 8 L / kg

Potassium carbonate = 1.2kg / kg

Methyl bromoacetate = 1.3 kg / kg

Strontium hydroxide = 1.5 kg / kg

PROCESS FLOW CHART

Stage - I

Citric acid

Water

Stage - II

Hot condition

Water

Stage -III

Hot condition

Methylene dichloride +

Chlorosulphonic acid

Quenching

Morpholine + methanol +

Malano nitrile + Suphur

Quenching

Acetone + Potassium carbonate +

Methyl bromoacetate

Filtration

Filtration & Concentration


Stage -IV

Water

Hot condition

17. PHENYRAMIDOL HYDROCHLORIDE

Stage-1: Synthesis of Phenyramidol Hydrochloride crude

Styrene Oxide

Water + Ethyl acetate


IPA.HCl

Centrifuge

2-Aminopyridine +DMF + Lithium

amide

Reaction mass

Organic layer

Phenyramidol Hydrochloride crude stage-1

Reaction with strontium hydroxide

Drying

Filtration



Stage-2 :Pure Phenyramidol Hydrochloride

Heating , filtration

Distillation

Acetone

Manufacturing process for Phenyramidol hydrochloride:

Stage-I: 2-Amino pyridine reacts with styrene oxide in the presence of lithium amide

to form the Phenyramidol hydrochloride crude.

Stage-II: Phenyramidol hydrochloride purified by using recrystallisation using

methanol and acetone to get pure Phenyramidol hydrochloride.

Methanol + Stage-1+activated

carbon

filtrate

Centrifugation, drying, milling

sieving & packing

Residue


18 IRON SORBITOL COMPLEX


citric acid

basification with Sodium Hydroxide

Ferric Chloride

filter, adjust pH with Citric acid

DNS DNS

Procedure: a solution Sorbitol , dextrin and citric acid in water is heated and

complexed with Ferric chloride solution in the presence of sodium hydroxide. pH is

adjusted with citric acid , filtered . the complex is isolated by adding DNS. which is

centrifuged and dried

Sorbitol + Water+dextrin

Reaction Mass

Filtrate

Centrifuge

Drying, Milling, Sieving, Packing


19 NAFTIFINE HYDROCHLORIDE:

Stage-I: Naftifine hydrochloride crude

Cinnamyl Chloride

Heat, centrifuge

Hydrochloric acid

Centrifuge, dry

Stage-II: Purification of Naftifine hydrochloride

Centrifuge, concentrate

Isopropyl alcohol

cool, Centrifuge

Manufacturing Procedure for Naftifine Hydrochloride.

Stage-I: N-Methyl –naphthyl- methanamine reacted with Cinnamyl chloride in the

presence of sodium bicarbonate in toluene to get Naftifine hydrochloride crude.

Stage-II: Stage-I purified by dissolving in methanol, charcolisation, filtration

concentration and isopropyl alcohol added to get Naftifine hydrochloride.

N-Methyl –naphthyl methanamine

+Sodium Bicarbonate+ Toluene

Stage-II + Methanol+activated carbon

stage-1

residue

Drying, Milling, sieving

centrifugate


20 ESMOLOL HYDROCHLORIDE MANUFACTURING FLOWCHART:

Stage-I

Malonic acid

Heat

Water

Stage-II:

hydrogen

gas

sulphuric acid

concentration

Stage-III:

Sodium Hydride

Epichlorohydrin

Water , Ethyl acetate

layer separation, concentration

Stage-IV

Isopropylamine

Concentration

Ethyl acetate, HCl

filtration

Stage-V:

Ethyl acetate

Acetone

Crystallization

4-Hydroxy benzaldehyde +

Pyridine

Reaction Mass

Centrifuge and Drying

Stage-I +

5% Pd/C + methanol

stage-II

Stage-II +

Dimethylformamide

Reaction

stage-III

Stage-III+ Methanol

Stage-IV

Esmolol Hydrochloride Centrifuge, Drying, Packing

Esmolol Base

Esmolol Hydrochloride

Crude


Manufacturing procedure of Esmolol Hydrochloride:

Stage-I : 4-hydroxy benzaldehyde condensed with malonic acid in the presence of

pyridine to give the 3-(4-hydroxyphenyl)acrylic acid (Stage-I).

Stage-II : Stage-I reduced with Hydrogen and Pd/C to get 3-(4-

hydroxyphenyl)propanoic acid . Which is esterified with methanol to get

methyl-3-(4-hydroxyphenyl)propanoate (Stage-II).

Stage-

III

: Stage-II condensed with Epichlorohydrin in the presence of sodium

hydride to get methyl-3-[4-(3-chloro-2-hydroxypropoxy)phenyl]

propanoate (Stage-III).

Stage-IV : Stage-III condensed with isopropyl amine to get Esmolol base, which is

treated with hydrochloric acid to get Esmolol hydrochloride

Stage-V : Stage-IV is re crystallised from ethyl acetate and acetone to get pure

Esmolol Hydrochloride.


21 CALCIUM L-5- METHYLTETRAHYDROFOLATE MANUFACTURING FLOW

CHART:

Stage-I: Synthesis of Calcium Methylfolate

Sodium Hydroxide

Dissolution

conc. HCl Sodium boro hydride

Centrifuge

Formaldehyde

Sodium Borohydride

acidify Conc.HCl

Centrifuge

Calcium chloride

Centrifuge

Stage-II: Synthesis of Methylfolate salt with S-phenylethylamine

Hydrochloric acid

Centrifuge

Water

S-phenyl ethyl amine

Centrifuge

DNS

Centrifuge, dry

Stage-III: Synthesis of Calcium-L-Methylfolate Crude:

L-Cysteine

Centrifuge

DNS, Acetone

Centrifuge ,dry

Process water+ Folic acid

Filtrate

Reaction mass

Stage-1

Wet Cake

Product (wet cake)

stage-II

Filtrate

stage-1

Stage-II + Water + DNS

Reaction mass

Wet Cake

stage-III


Step-IV: Purification of Calcium-L-methylfolate:

Water

Heating & Cooling

Manufacturing process for the preparation of Calcium L-Methylfolate:

Stage-I: a solution of Folic acid in sodium hydroxide is reduced using Sodium

borohydride to tetrahydrofolate ,which is reaced with formaldehyde to get 5,10-

methyene tetrahydrofolate this is hydrolysed and reduced by sodium borohydride to

get Calcium DL- methylfolate.

Stage-II: Calcium DL- methylfolate reacted with S-phenyl methylamine to get the S

salt.

Stage-III: a solution of The above amine salt is treated with calcium chloride to get

L-methyl folate crude Stage-IV: Calcium L-Methylfolate crude is purified in water to

get pure Calcium L-methyl folate.

22 MINOXIDIL:

PROCESSES FLOW CHART

Stage-I: Preparation of Urea Hydrogen peroxide adduct

Urea

cool, centrifuge

Stage-II : Preparation of n-Oxide

a) Preparation of catalyst solution

Stage-I addition

b) Preparation of n-Oxide

Catalyst solution

Centrifuge

Stage-III

Reaction

Drying, milling, Sieving, Packing

Water+ Hydrogen peroxide

Stage-I

Carbinol+ Phthalic anhydride

Catalyst solution

Carbinol +2,4 diamino-6-

chloropyrimidine

Stage-II

cen


Stage-III: Preparion of Minoxidil crude

Distilation

Cooling & Centrifuge

Stage-IV: Purification

Heating

Cooling & Centrifuge

Manufacturing procedure of Minoxidil:

Stage-I: Preparation of Urea Hydrogen peroxide adduct

Hydrogen peroxide (50%) reacts with urea to form the urea hydrogen peroxide

adduct.

Stage-II: Preparation of n-Oxide

a) The catalyst solution is prepared by the reaction of urea hydrogen peroxide adduct

and phthalic anhydride in carbinol.

b) The above catalyst solution is added to a solution of 2,4 diamino-6-chloropyrimidine

in carbinol and warmed. The precipitated oxide is cooled and centrifuged.

Stage-III: Preparation of Minoxidil crude

Minoxidil crude is prepared by reacting Piperidine with stage-II at 60-70 deg C.

Product was isolated by centrifugation.

Stage-IV: Purification of Minoxidil crude

Minoxidil Crude purified by using carbinol to get pure Minoxidil.

23 MEBEVERINE HYDROCHLORIDE


STAGE-I:- Synthesis of 4-bromobutyl-3,4-dimethoxybenzoate

1,4-Dibromobutane

High vaccum distillation

Piperidine+ Stage-II

Minoxidil crude + Methanol

Reaction mass

Stage-III

Drying, milling, sieving & packing

Veratric acid +

Potassium Hydroxide

Stage-I


STAGE-II: Synthesis of Mebeverine Hydrochloride crude

Methyl isobutyl

ketone

Potassium carbonate

Heat and filter

Water layer separation,

concentration

Centrifuge IPA. HCl

STAGE-III: Purification

Methyl isobutyl ketone

filter, concentrate and centrifuge

Manufacturing Procedure for Mebeverine Hydrochloride:

Stage-I : Veratric acid reacts with 1,4-dibromocompound in the presence of

potassium hydroxide to form the 4-bromobutyl-3,4-dimethoxybenzoate.

Stage-II : Stage-I reacts with 1-(4-methoxyphenyl)-2-ethylaminopropane in the

presence of sodium carbonate in Methyl isobutyl ketone to form the

Mebeverine Hydrochloride crude.

Stage-III: Stage-II purified by Methyl isobutyl ketone to get pure Mebeverine

Hydrochloride.

24 TERBINAFINE HYDROCHLORIDE:

Stage-I: Terbinafine hydrochloride crude

Chloro-6,6-dimethyl-2-hepten-4-yne

Heat, centrifuge

Hydrochloric acid

centrifuge, dry

1-(4-methoxyphenyl)-2-

ethylaminopropane

+

MBH-Stage-I

filtrate

residue

Mebeverine Hydrochloride

Crude

Mebeverine Hydrochloride

Crude +activated carbon

Packing, Drying, Milling, Sieving

N-Methyl –naphthyl methanamine

+Sodium carbonate+ Toluene

stage-1

centrifugate

https://en.wikipedia.org/wiki/Methyl_isobutyl_ketone







Stage-II: Purification of Terbinafine hydrochloride

Centrifuge, concentrate

cool, Centrifuge

Manufacturing Procedure for Terbinafine Hydrochloride.

Stage-I: N-Methyl –naphthyl- methanamine reacted with 1-Chloro-6,6-dimethyl-2-

hepten-4-yne in the presence of sodium carbonate in toluene to get terbinafine

hydrochloride crude.

Stage-II: Stage-I purified by dissolving in methanol, charcolisation, filtration

concentration and isopropyl alcohol added to get terbinafine hydrochloride.

7.0 RAW WATER REQUIREMENT

A fullfledged ETP with 3 stage RO/Evaporator provided to recycle the treated waste

water in process, and make-up water met through SIPCOT supply.

The Plant operates at present, and will operate on expansion on Zero Discharge basis.

The entire waste water is, will be treated & reused. There will be no discharge of waste

water from the Plant.

The additional make-up water requirement is met through SIPCOT sources. There is no

drawal of ground or surface water from the plant.

Stage-II + isopropanol +activated carbon

residue

Drying, Milling, sieving


Water Balance Diagram

All Values are in KLD Existing [ ] Proposed ( )

Evapora tion [14.0] + (7.5) = 21.5

Waste w ate r [34.0] + (24.5) = 58.5

Evaporation [7.5] + (12.0) = 19.5

Waste w ate r [4.5] + (6.5) = 11.0

Evaporation [1.0] + (1.2) = 2.2

Waste w ate r [4.0] + (4.8) = 8.8

Tre ate d Dom e stic Se w age [4.0] + (4.8) = 8.8

P e rm e ate Re cycle d w ate r [30.5] + (24.8) = 55.3

RO Re je ct Re cycle d w a te r [7.5] + (5.9) = 13.4

[65.0] + (56.5) = 121.5

Cooling / Boiler Make-up

[12.0]+(18.5) = 30.5

Process/ Floor wash / Equipment Cleaning [48.0] + (32.0) = 80.0

Domestic Consumption

[5.0] + (6.0) = 11.0

Garden [4.0] + (4.8) = 8.8

ETP [38.5] + (31.0)

= 69.5

RO

SIPCOT

[27.0] + (25.8) = 52.8

ME

[3

0.5

] +

(2

4.8

) =

5

5.3

Crystalization/ Handling /

Evaporation

0.8

[8

.0 +

(6

.2) =

1

4.2

[38.0] + (30.7) = 68.7

STP

Pre-Feasibility Report GCPL

60

8.0 ENERGY CONSUMPTION

The details of existing and upon expansion power consumption and its source are as

follows:

Power Consumption

Source Existing Proposed Upon Expansion

Captive Windmill through

TNEB Grid

0.48 MW 0.32 MW 0.8 MW

Global Calcium has its own windmill, and the entire power required is met through this

windmill. The plant runs entirely on this green energy.

D.G. Sets of 180 KVA x 1, 380 KVA X 1, & Proposed 250 KVA X 1 capacity will be used only

during emergency or grid failure.

9.0 WORK FORCE

The existing work force of 70 Nos. proposed additional will be 80 Nos. and upon expansion

the total work force will be 150 Nos.

10.0 EXISTING ENVIRONMENTAL SCENARIO

10.1 Air Environment

Ambient air quality monitoring was carried out for 4-locations, one in the plant site and 3 in

different directions outside the plant site, the location of sampling station is given in the

following Table and as shown in Fig 2.0.

Pre-Feasibility Report GCPL

61

Fig 2.0 Location of Ambient Air Quality Monitoring Stations

SA1

SA2

SA3

SA4

Pre-Feasibility Report GCPL – Unit III

62

Locations of Air Monitoring Stations

S. No. Code Sampling Station Direction to

proposed project

site

Distance from

proposed project

site (km)

1 SA1 Existing Plant - -

2 SA2 Santanapura Agraharam N 2.0

3 SA3 TVS Nagar SSW 3.5

4 SA4 Sanamavu SE 4.0

Summary of air quality data

Location Station Concentration g/Nm

3

Code SO2 NO

X PM

10 PM

2.5

Existing Plant SA1 12-31 23-38 28-66 15-22

Santanapura Agraharam SA2 8-16 9-18 37-58 16-24

TVS Nagar SA3 10-18 10-19 33-54 17-28

Sanamavu SA4 10-19 12-20 40-59 18-28

Overall 8-31 9-38 28-66 15-28

The Concentration of Ozone (O3), Lead (Pb), Carbon Monoxide (CO), Ammonia (NH3),

Arsenic (As), Nickel (Ni) Benzene (C6H6) and Benzo(a)Pyrene were Below Deductable

Level (BDL) in all locations.


63

10.2 Noise Environment

Noise level measurements, with 5 minutes interval, in four corner of plant site were carried

out.

The observed ambient instantaneous noise levels at the plant site varied in the range of

63.5dB(A) – 72.2 dB(A) with most of the observed values less than 65 dB(A).

10.3 Water Environment

The ground/surface water quality in the study area, normally meets the desirable/essential

limits. The locations of water sampling stations marked in Fig 3.0 and the results are given

in the following Table.

Locations of Water Sampling Stations


proposed project

site

Distance from

proposed project

site (km)

1 SW1 Existing Plant - -

2 SW2 Santaarpura Agraharam

(Borewell)

N 2.0

3 SW3 TVS Nagar (Borewell) SSW 3.5

4 SW4 Hosur (Lake) S 0.5


64

Fig 3.0 Location of Water Sampling Stations

SW1

SW2

SW3

SW4


65

Water Quality Data

S.No Parameters SW1 SW2 SW3 SW4

1 Colour (Hazen units) <1 <1 <1 <1

2 Odour Agreeable Agreeable Agreeable Agreeable

3 Total Suspended Solids, mg/l 16 15 17 18

4 Dissolved Solids mg/l 520 630 432 1205

5 PH Value 7.0 7.2 7.6 7.5

6 Temperature in oC 32 32 32 32

7 Oil & Grease, mg/l BDL BDL BDL BDL

8 Total Residual Chlorine, mg/l BDL BDL BDL BDL

9 Nitrate as No3, mg/l 14.14 16.12 0.06 22.10

10 B.O.D (3 days 27oC), mg/l 16 18 3 11

11 Arsenic (as As), mg/l BDL BDL BDL BDL

12 Mercury (as Hg), mg/l BDL BDL BDL BDL

13 Lead (as Pb), mg/l BDL BDL BDL BDL

14 Cadmium (as Cd), mg/l BDL BDL BDL BDL

15 Hexavalent Chromium (as

Cr+6), mg/l

BDL BDL BDL BDL

16 Total Chromium (as Cr), mg/l BDL BDL BDL BDL

17 Copper (as Cu), mg/l BDL BDL BDL BDL

18 Zinc (as Zn), mg/l 0.02 0.02 <0.01 0.05

19 Selenium (as Se), mg/l BDL BDL BDL BDL

20 Nickel (as Ni), mg/l BDL BDL BDL BDL

21 Boron (as B), mg/l BDL BDL BDL BDL

22 Percent Sodium 26 33 21 30

23 Cyanide (as CN), mg/l BDL BDL BDL BDL

24 Chloride (as Cl), mg/l 290 286 104 464

25 Fluoride (as F), mg/l 0.3 1.0 Nil 1.2

26 Sulphate (as SO4), mg/l 136 155.06 4 160.8

27 Pesticides Nil Nil Nil Nil

28 Total Coliform Organisms,

(MPN/100ml)

6 8 5 18

29 Phenolic Compounds (as C6

H5 OH), mg/l

Nil Nil Nil Nil


66

10.4 Soil Environment

A total of 4-samples was collected in and around the plant site. Samples were collected

using augers at depths upto 30, 60 and 100 cms. The Soil Samples were analysed for pH,

electrical conductivity, nitrogen, phosphorus, potassium, available magnesium,

natural moisture content, grain size distribution (gravel, sand, clay/silt) textural

class, bulk density, plastic limit, liquid limit etc. The undisturbed sample at 60 cm

depth was analysed for field capacity, wilting coefficient, and available water storage

capacity. The results are given in the following Table.

Locations of Soil Sampling Stations


proposed project

site

Distance from

proposed project

site (km)

1 SS1 Existing Plant - -

2 SS2 Santanapura Agraharam N 2.0

3 SS3 TVS Nagar SSW 3.5

4 SS4 Sanamavu SE 4.0

Location of the sampling stations are marked in Fig 4.0.


67

Fig 4.0 Location of Soil Sampling Station

SS1

SS2

SS3

SS4


68

Soil Quality Data

No Location SS1 SS2 SS3 SS4

1. Depth, cm 0-30 30-60 60-100 0-30 30-60 60-100 0-30 30-60 60-100 0-30 30-60 60-100

2. PH 6.5 6.05 6.4 6.7 6.65 6.7 6.8 6.65 6.7 6.8 6.75 6.6

3. Electrical Conductivity ( mho/cm)

10.5 11.1 11.0 12.6 12.9 12.5 13.5 13.0 13.4 11.1 13.3 12.5

4. Moisture Content (%) 5.0 4.5 6.0 4.5 5.1 6.05 3.0 7.5 8.0 10.0 11.5 10.0

5. Organic matter (%) 1.85 1.98 1.5 1.1 1.4 1.25 1.13 1.24 1.2 1.98 2.46 2.38

6. Alkalinity 0.005 0.005 0.005 0.0051 0.0052 0.0051 0.0052 0.0055 0.0051 0.0052 0.0052 0.0053

7. Acidity Nil Nil Nil Nil Nil Nil Nil Nil Nil Nil Nil Nil

8. Sodium Absorption Ratio 0.11 0.1 0.1 0.1 0.09 0.1 0.13 0.11 0.11 0.08 0.090 0.08

9. Nitrogen (as N, %) 0.004 0.004 0.005 0.001 0.001 0.001 0.003 0.004 0.004 0.005 0.003 0.003

10. Phosphorus (as P, %) 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001

11. Potassium (as K, %) 0.01 0.008 0.01 0.007 0.006 0.006 0.009 0.01 0.001 0.009 0.01 0.008

12. Iron (as Fe, %) 0.8 0.84 0.75 0.55 0.6 0.55 0.51 0.55 0.5 1.07 1.0 1.05

13. Copper (as Cu, %) 0.003 0.003 0.002 0.001 0.001 0.001 0.002 0.002 0.002 0.003 0.003 0.003

14. Zinc (as Zn, %) 0.01 0.01 0.01 0.004 0.003 0.001 0.005 0.005 0.005 0.010 0.005 0.005

15. Manganese (as Mn, %) 0.02 0.02 0.02 0.009 0.009 0.01 0.02 0.02 0.02 0.020 0.02 0.02

16. Boron (as B, ppm) 0.2 0.2 0.22 0.2 0.24 0.21 0.25 0.2 0.21 0.22 0.24 0.21

17. Sodium chloride (as Nacl, %) 0.013 0.016 0.013 0.009 0.008 0.008 0.01 0.01 0.01 0.060 0.04 0.05

18. Sodium Carbonate (as

Na2CO3,%)

0.006 0.004 0.004 0.01 0.01 0.009 0.009 0.01 0.01 0.01 0.01 0.01

19. Texture Sandy Sandy Sandy Sandy Sandy Sandy Sandy Sand Sandy Sandy Sandy Sandy

20. Sand, % 89.45 89.05 89.2 90.4 90.15 90.05 84.4 84.95 84.25 88.55 88.1 87.9

21. Silt & Clay, % 10.5 10.85 10.75 9.55 9.8 9.95 15.6 15.05 15.7 11.45 11.8 12.05

22. Specific gravity, g/cc 2.37 2.38 2.39 2.55 2.5 2.48 2.45 2.5 2.52 2.5 2.53 2.48

23. Bulk Density, g/cc 1.09 1.0 1.03 1.16 1.14 1.1 1.09 1.15 1.14 1.09 1.09 1.13

24. Infiltration Capacity (in cm/hr) 5.0 3.1 2.5 5.5 1.9 1.2 5.8 2.05 1.7 5.4 1.8 1.05

25. Arsenic as As (mg/kg) BDL BDL BDL BDL BDL BDL BDL BDL BDL BDL BDL BDL

26. Cadmium as Cd (mg/kg) BDL BDL BDL BDL BDL BDL BDL BDL BDL BDL BDL BDL

27. Chromium as Cr (mg/kg) BDL BDL BDL BDL BDL BDL BDL BDL BDL BDL BDL BDL

28. Lead as Pb (mg/kg) BDL BDL BDL BDL BDL BDL BDL BDL BDL BDL BDL BDL

29. Mercury as Hg (mg/kg) BDL BDL BDL BDL BDL BDL BDL BDL BDL BDL BDL BDL


69

11.0 WASTE & WASTE MANAGEMENT

11.1 Air Pollution

The major sources of air emissions are from fuel burning in the Boiler in the existing

operation, and Volatile Organic Compounds (VOC) from the proposed operation.

Emissions from combustion of fuels

The emissions are from Diesel Generator & Wood fired boiler.

The Diesel Generator is used only when there is an electrical supply breakdown.

The Wood fired boiler capacity is of 3 T. The stack is to a height of 30 m as per the norms.

It will be ensured that the fuel used will have low sulphur, optimum air fuel ratio to limit

NOx emission. Moreover, the fuel used is wooden briquette, which is most environment

friendly.

Emissions from production process

The emissions from proposed production process are mainly from the reactor and solvent

storage area. The reactors and solvent storage area are proposed to be provided with

adequate measures as fallows.

Each reactor is connected to 2-consecutive condensers for recovery of solvent residue.

The Reactors after condenser are connected to a Scrubber of 4000 m³/hr capacity. Solvent

will be absorbed in water and water + Solvent mixture are taken to stripper to separate the

solvent and water.

All Underground tanks vent are connected through 25NB pipeline to 1m² condenser with

chilled water coolant 15°C, condensed solvent are collected in a receiver. Mixed solvent are

taken for process based on suitability.

Stored solvents are non-volatile which are having high Boiling point (>65°C) and vapour

pressure is also very less.


70

11.2 Wastewater Generation

Description Quantity (m³/day)

Existing Proposed

Additional

Upon

Expansion

Process / Floor Wash / Equipment Cleaning 34.0 24.5 58.5

Cooling Water / Boiler Blowdown 4.5 6.5 11.0

Domestic Sewage 4.0 4.8 8.8

TOTAL 42.5 35.8 78.3

11.2.1 Wastewater Management

At GCPL (Unit III), trade effluent is generated from the floor washings and

equipment cleaning. The total quantity of this trade effluent generated upon

expansion will be 69.5 KLD. Existing trade effluent of 38.5 KLD is treated in the

existing ETP/RO/MEE and reused in the process. Proposed additional quantity of

generation of trade effluent of 31 KLD will be treated in proposed ETP/RO/MEE and

reused in process.

The trade effluent generated from floor washings/equipment cleanings is collected in

a collection tank.

At the inlet of the tank, hydrated lime slurry is added to effect neutralisation.

The neutralised waste is then pumped to flow control tank, from where the waste is

allowed to discharge into a settling tank.

The overflow from the settling tank is allowed to pass through a three stage

anaerobic contact filter.

After anaerobic treatment, the waste is aerobically treated in an aerated lagoon.

The treated wastewater from the lagoon is allowed to settle in a settling tank and is

pumped to aerated lagoon II, wherein polyelectrolyte is added for better floc

formation to enable easy settling of suspended particles.

The aerated water is then taken to settling tank II, from where the clear supernatant

is pumped into the collection tank.

The treated water is then passed through the RO plant. Treated water from RO is

reused and the RO rejects are subject to Mechanical evaporation. Condensed water

from Mechanical evaporator is also reused.

Upon expansion the Domestic sewage of 8.8 KLD will be treated in STP and reused

for greenbelt development within the plant premises.


71

11.3 Solid Wastes

Sl.

No.

Type of Solid Waste Quantity

TPA

Disposal/Treatment

Existing

1. Spent catalyst / spent carbon 2.0 Stored in HDPE Bags used for



water treatment



3. Used/spent oil 0.2 Recover and Reuse-CPCB

Authorized recyclers

Proposed Expansion

1. Ash from Boiler 200 Sold to brick manufactures


water treatment plant


Common Landfill

3. Concentration or evaporation

residues

105 Stored in HDPE Bags used for

Common Landfill

4. Process Residue and wastes 145 Stored in HDPE Bags used for

Common Landfill

5. Spent Solvent 30 Authorized recyclers

Hazardous wastes from the production process are collected and stored in closed containers.

The containers containing the Hazardous waste is stored in a closed shed. The Hazardous

waste is disposed to common waste collection yard of Tamil Nadu Waste Management

Limited at Gummidipoondi, Tiruvallur District.

Sewage Sludge / Sludge from Effluent Treatment

The sewage is connected to SIPCOT sewage system and hence no sewage sludge is

collected within the premises.

The sludge from the effluent treatment is dried in Filter Press. The dried sludge is packed in

polythene woven / polythene bags and the sludge bags are stored in a closed shed. The

hazardous sludge will be disposed to common waste collection yard of Tamil Nadu Waste

Management Limited at Gummidipoondi, Tiruvallur District.

12.0 CONCLUSION

The proposed expansion is planned within the existing premises of GCPL-Unit III located

at # 19, 19B SIPCOT Industrial Complex, Hosur – 635 126, Tamil Nadu, which is a notified

industrial estate in Tamil Nadu. More-over the plant with modern process and techniques

including efficient environment management plan viz., air pollution control system to limit

air emissions, treatment of effluent in a full-fledged ETP / 3 stage RO and disposal of solid

waste in common landfill as authorized will all result in insignificant impact on the ambient

environment.

global calcium private limited unit...

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