Form-1 and PRE FEASIBILITY REPORTenvironmentclearance.nic.in/writereaddata/FormB/TOR/PFR/...M/s Ratantray Pharmaceuticals Pvt Ltd Proposed manufacturing plant for Vitamins, Steroids

M/s Ratantray Pharmaceuticals Pvt Ltd Proposed manufacturing plant for Vitamins, Steroids & Hormones at H1-174 RIICO, Shree Khatushyam Ji Industrial Area, Reengus, District-Sikar, Rajasthan

Form-1 and PRE FEASIBILITY

REPORT

For Greenfield Facility of Manufacturing of Vitamins,

Steroids & Hormones At

H1-174 RIICO Shree Khatu Shyam Ji Industrial Area, Reengus, District Sikar, State- Rajasthan

For

M/s Ratantray Pharmaceuticals Pvt. Ltd.

Environment Consultant Vardan Environet

(QCI and NABET/EIA/1619/RA 0037) D-142, Sushant Lok-III, Sector 57

Gurgaon (Haryana) Contact no.- 9810355569

Mail ID: [email protected] Contact No. 0124-4291036, 09899651342

mailto:[email protected]


PRE-FEASIBILITY REPORT 1. INTRODUCTION Earlier, the assessment of the projects was done on Technical feasibility reports and Cost-Benefit-Ratio which mainly considered financial & technical resources. But no consideration was given to the environment protection in this evaluation and these flaws became apparent with continuous deterioration of environment. Thus in order to have more realistic evaluation, and keeping in view the deteriorating conditions, another dimension was added which is now called as “Environmental Impact Assessment” (E.I.A.). This forms an integral part of the project and is taken into account while appraising the project at different stages. Thus in the new comprehensive approach all considerations like, Technical, Financial & Environmental are given due weightage. M/s Ratantray Pharmaceuticals Pvt. Ltd. is proposing a project for manufacturing of Vitamins, Steroids & Hormones at H1-174 RIICO, Shree Khatushyam Ji Industrial Area, Reengus, District-Sikar, Rajasthan. The location of proposed unit is ideal for the point of view of market of the Finished Goods & raw materials for manufacturing of such types of Bulk Drugs & intermediates. There are lots of organized and un-organized manufacturer situated in these area. The availability of raw materials and marketing of finished goods will be no problem for proposed industry.

Table-1 List of Raw Material S. No. Raw Material Unit Quantity Standard

(5.0kg batch size) Per Month

(110kg/month) Per Year

(Kg) 1 Cyanocobalamin Kg 5.00 100 1200 2 Methyl Iodide Kg 4.50 90 1080 3 Sodium

Borohydride Kg 5.50 110 1320

4 Chloroform Kg 98.00 1960 23520 5 Acetone Kg 60.00 1200 14400 6 Phenol Kg 25.00 500 6000 7 Methanol Kg 13.00 260 3120

Table-2 List of Products

S. No. Vitamins 1 Methylcobalamin ( Vitamin B12) 2 Hydroxocobalamin Acetate 3 Alfacalcidol (Vitamin D) 4 Ascorbic Acid (Vitamin C) 5 Calcitriol (Vitamin D3) 6 Ergocalciferol (Vitamin D2)


7 Paricalcitol (Vitamin D2) 8 Pyridoxal 5 Phosphate (Vitamin B6)

Steroids 1 Beclomethasone dipropionat 2 Betamethansone dipropionate 3 Betamethansone sodium phosphate 4 Betamethansone Valerate 5 Dexamethasone sodium phosphate 6 Clobetasole Propionate 7 Methyl prednisolone Acetate 8 Prednisolone Acetate 9 Methyl prednisolone

10 Prednisolone Sodium Phosphate 11 Prednisolone 12 Mometasone furoate diropotionate 13 Deflazacort 14 Budesonide

Hormones 1 Testosterone 2 Testosterone Cypionate 3 Testosterone Enanthate 4 Testosterone Propionate 5 Testosterone Decanoate 6 Testosterone Acetate 7 Testosterone Phenylpropionate 8 Nandrolone 9 Nandrolone Decanoate

10 Trenbolone Enanthate 11 Norethisterone 12 Norethisterone Acetate 13 Norethisterone Enanthate

As per EIA Notification dated 14th Sept., 2006 and amended from time to time, the proposed project falls under Category “B”, Project or Activity 5(f) Synthetic organic chemical Industry. They have to submit Form-I along with Pre-Feasibility Report and other relevant documents for getting Environmental Clearance. This pre-feasibility report has, therefore, been prepared by the consultant to assess the likely impact of the proposed project on various factors which may be affected with the implementation of the program and to suggest remedial/precautionary measures, if any. 2. Need for installation of project


India ranks third with respect to the production capacity of pharmaceuticals in the world, whereas in terms of value, India is in 14th place. The total turnover of pharmaceutical industry in 2010 was US $ 20 billion, which is 20 times when compared with the turnover in 1990 (Indian Pharmaceutical Industry, 2010). All major therapeutic groups of drugs are manufactured in India. In terms of generics production India ranks 4th, but in terms of export value India ranks 17th. The need is increasing every year due to continual growth of pharmaceutical industry. This project is expected to contribute in partially fulfil the demand of pharmaceutical industries. 3.0 BASELINE ENVIRONMENTAL SETTING 3.1 The State Rajasthan is India's largest state by area (342,239 square kilometres (132,139 sq meter) or 10.4% of India's total area). It is located on the western side of the country, where it comprises most of the wide and inhospitable Thar Desert (also known as the "Rajasthan Desert" and "Great Indian Desert") and shares a border with the Pakistani provinces of Punjab to the northwest and Sindh to the west, along the Sutlej-Indus river valley. Elsewhere it is bordered by five other Indian states: Punjab to the north; Haryana and Uttar Pradesh to the northeast; Madhya Pradesh to the southeast; and Gujarat to the southwest. Major features include the ruins of the Indus Valley Civilization at Kalibanga; the Dilwara Temples, a Jain pilgrimage site at Rajasthan's only hill station, Mount Abu, in the ancient Aravalli mountain range; and, in eastern Rajasthan, the Keoladeo National Park near Bharatpur, a World Heritage Site known for its bird life. Rajasthan is also home to three national tiger reserves, the Ranthambore National Park in Sawai Madhopur, Sariska Tiger Reserve in Alwar and Mukundra Hill Tiger Reserve in Kota.The state was formed on 30 March 1949 when Rajputana – the name adopted by the British Raj for its dependencies in the region was merged into the Dominion of India. Its capital and largest city is Jaipur, also known as Pink City, located on the state's eastern side. Other important cities are Jodhpur, Udaipur, Bikaner, Kota and Ajmer. 3.2 District Sikar The district is located in the north-eastern part of the state of Rajasthan. It is bounded on the north by Jhunjhunu district, in the north-west by Churu district, in the south-west by Nagaur district and in the south-east by Jaipur district. It also touches Mahendragarh district of Haryana on its north-east corner. The district has an area of 7742.44 km² and a population of 26,77,737 (2011 census). Sikar, Churu district and Jhunjhunu district's comprise the Shekhawati region of Rajasthan. The old name of Sikar was "Veer Bhan Ka Bas"

3.3 Project Site The Plant site is located at H1-174 RIICO, Shree Khatushyam Ji Industrial Area, Reengus, District-Sikar, Rajasthan It lies near Lat: 27°19'59.376” and Long: 75°35'21.037”E and is at an Altitude of about 472m above mean sea level. The nearest railway station is Reengus Railway

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

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

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

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

https://en.wikipedia.org/wiki/Punjab,_Pakistan

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

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

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

https://en.wikipedia.org/wiki/Punjab,_India

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

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



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

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

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

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

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



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

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

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

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

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



https://en.wikipedia.org/wiki/Bharatpur,_India

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

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

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

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

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



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

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

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

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

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

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

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

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

https://en.wikipedia.org/wiki/Kota,_Rajasthan

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

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

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

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

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

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

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



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

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

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

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



Station which is at a distance of about 4 km from the project site. It is about 2.30 km from NH-11.


Figure 1 : Google Image 10 Km Buffer Map


Fig 2: Key Plan of Project Site


Fig 3: Layout Plan Ground Floor


Fig 4: Layout Plan First Floor 4.0 PROJECT DESCRIPTIONS 4.1 General The Plant site is located at H1-174 RIICO, Shree Khatushyam Ji Industrial Area, Reengus, District-Sikar, Rajasthan. It lies near Lat: 27°19'59.376” and Long: 75°35'21.037”E and is at an Altitude of about 472 m above mean sea level. The nearest railway station is Reengus Railway Station which is at a distance of about 4 km from the project site. It is about 2.30 km from NH-11. M/s Ratantray Pharmaceuticals Pvt Ltd has taken an existing industry land which is permanently closed. The total land area is 500 Square meter out of which approx 33% of the total area will be covered as Green Belt. The existing plant will be dismantled and after that a new plant will set up. The total cost of the project will be 140 Lakhs.


Table-3 Plant and Machinery S.No. Particulars Number Capacity 1 Cooling Tower 2 200 TR 2 Chilling plant 3 26 TR 3 Hot Water System 2 2 KL 4 D.G. Set 1 60 KVA 5 Electric Heater 1 200 Kg 6 Vacuum Pump 1 20 HP 7 Air handling handing 1 3000 C.F.M

Table-4 Plant Site and Location

S. No Particulars Details 1 Location a Village/ Town/Plot No. H1-174 RIICO, Shree Khatushyam Ji Industrial Area, Reengus b Tehsil Srimadhopur c District Sikar d State Rajasthan e Latitude 27°19'59.376"N d Longitude 75°35'21.037"E 2 Elevation 472m 3 Land use at the project

site Industrial

4 Climatic Conditions Temperature

Rainfall Min: 5oC, Max:45oC 459.8 mm (Normal)

5 Nearest highway NH-11 is 2.30 km (approx) in East. SH-37C is 11 km (approx) in East.

6 Nearest railway station Reengus Railway Station is 4 km (approx) in North. 7 Nearest airport Jaipur International Airport is 60 km (approx) in South

East. 8 Nearest major city Reengus is 3 km (approx) in North. 9 Nearest major

settlement Reengus is 3 km (approx) in North.

10 Features with 10 km : i) Defense installations Nil ii) Archaeological

important places Nil

iii) Wild life sanctuaries Nil Iv) Reserved/Protected

forest Nil

v) Rivers Mendha River is at 1.6km (approx) in North West. vi) Hill ranges Nil


vii) State Boundary No

4.2 MANUFACTURING PROCESS: 1 VITAMIN 1.1. ALFACALCIDOL (Vitamin D) CHEMICAL REACTION SEQUENCE OF ALFACALCIDOL

Process: 1 6-Hexamethylene-bis-cyanoguanidine reacts with 2-Ethylhexylamine hydrochloride and heated at 150-155ºC. The mixture is cooled and the the product is dissolved in hot water. The solution is treated with activated charcoal convert the alfacalcidol crude Alfacalcidol crude purified with Methanol filter with hyflow bed to get pure alfacalcidol, which is further dried and packed. 1.2. ASCORBIC ACID (Vitamin C) CHEMICAL REACTION SEQUENCE OF VITAMIN C (Ascorbic Acid)

Process: 2-keto-1-gulonic acid reacts with substantially anhydrous Acetic acid catalyst in presence of acetone to convert the ascorbic acid crude. Ascorbic acid crude purified with methanol and Purified water filter with hyflow bed to get pure ascorbic acid, which is further dried and packed.


1.3. CALCITRIOL (Vitamin D3) CHEMICAL REACTION SEQUENCE OF CALCITRIOL

Process: A solution of 1 α.25-diacetoxyprecholecalciferol, potassium hydroxide and methanol Stirred at room temperature under argon for 30 hours. The reaction mixture concentrated under reduced pressure. Water added to the residue and the mixture is extracted With methylene chloride. The combined organic extracts washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, Filtered and evaporated under reduced pressure to give l α, 25dihydroxyprecholecalciferol as a thick oil. A solution of l α.25-dihydroxyprecholecalciferol in dioxane and heated under reflux for 30 minutes under an atmosphere of argon gas. The reaction mixture is concentrated under reduced pressure and filters the residue. Purified the Material through column chromatography with mixture of ethyl acetate and n-hexane as the eluent. Re-crystallize the material with methyl formate of l α,.25dihydroxcholecalciferol as colorless crystals, which is further dried and packed. 1.4. PARICALCITOL (Vitamin D2) CHEMICAL REACTION SEQUENCE OF PARICALCITOL (Vitamin D2)

Process: Paricalcitol Crude dissolve in acetone in a sonicator at 28º for 15 minutes than filter through glass wool than the solution is concentrated by evaporation. The solution is cooled to -18 º C for 20 hrs. The crystal is filtered and washed with cooled acetone Paricalcitol which is further dried and packed.


1.5. PYRIDOXAL-5 PHOSPHATE (Vitamin B6) CHEMICAL REACTION SEQUENCE OF PYRIDOXAL-5 PHOSPHATE (Vitamin B6)

Process: p-toluidine dissolved in 85% Orthophosphoric Acid and phosphorus pentoxide stirring the solution for 6 hrs at 45ºC and hydrolyzed for 50 minutes at 60ºC then add 0.1 N hydrochloric acid to adjust the pH 3 then add 50% NaoH with Stirring Under cooling 6-chloro-3-indolyl phosphate p-toluidine is obtained. 6-chloro-3-indolyl phosphate p-toluidine dissolve in 2N Sodium hydroxide then extract with Chloroform. Add 2N HCL then stand the Rxn Mass for one day in cool condition. Filter the material and washed with ethyl alcohol and which is further dried and packed. 1.6. METHYLCOBALAMIN (Vitamin B12) CHEMICAL REACTION SEQUENCE OF METHYLCOBALAMIN (Vitamin B12) Process:


Step-I: Check the Glass flask is cleaned and dry. Charge Process water, heating and addition of cynocobalamin. Cooling and addition of sodium borohydride, stirring and addition of methyl iodide. Addition of chloroform and phenol mixure, stirring, settling for layer separation. Step-II: Check the Glass flask clean and dry. Charge process water, organic layer, chloroform and acetone. Stirring settling, layer separation, distillation of process water. Addition of acetone, cooling, filtration, drying, sieving

Flow Diagram of Manufacturing process of METHYLCOBALAMIN


2. Steroids 2.1. Beclomethasone Di Propionate Reactions Stage: 1st

Stage: 2nd


Stage: 3rd

Stage: 4th

Manufacturing Process: -

1. Clean & check the entire machine used for production in all respect before use. 2. Charging of HCL


3. Cool up to -100C 4. Addition of DB-XI 5. Stirring for 30 minutes. 6. Rx / mass quenching in D.M. Water 7. Stirring 8. Addn. of KOH solution 9. Stirring 30 minutes 10. Filtration & wash with D. M. Water 11. Washing with Chloroform 12. Washing with Ethyl Acetate 13. Drying , In process testing (Beclo. Base). 14. Charging of Methylene Chloride 15. Charging of Beclomethasone Base 16. Heat to Reflux 17. Addn. of T.E.O.P. 18. Distill out Methylene Chloride 19. Addn. of PTSA 20. Addn. of Ethyl Acetate 21. Reflux the Rx. Mixture at 55 ºC 22. Cool the Rx. Mixture at 25 ºC 23. Then add Orthophosphoric Acid 24. And the Rx. Mixture at 25 ºC 25. Filtration & Washing with 26. Charging of Acetone 27. Filtration & Washing with Acetone 28. Charging of Acetone 29. Rx / Mass Quinch in D.M. Water 30. Filtration and Washing with D.M. Water 31. Drying, In process testing (B.M.P.) 32. Charging of Pyridine 33. Charging of B.M.P. (Dry) & cooling 34. Addn. of Propionic Anhydride. 35. Add. D.M. Water 36. Stirring 37. Filtration and washing with DM water. 38. Drying, in process testing (Beclo. Crude) 39. Charging of Acetone 40. Charging of Beclo. Crude


41. Add Activated Carbon and filter it over hyflowbed 42. Cooling 43. Rx / Mass Quench in D.M. Water 44. Filtration & washing with D.M. Water 45. Drying , In Process Testing (Beclomethasone Dipropionate ) 46. Final Quality Control sampling to be done for complete analysis. 47. Release the material after obtaining the results from Quality Control. 48. Packed in specified containers with proper label.

2.2. CHEMICAL REACTION SEQUENCE OF BETAMETHANSONE VALERATE

HO

OF

+O

OO

CH3

CH3

H3CH3C

Methylene chloride

Betamethasone Trimethyl Ortho Valerate

C

CH3

CH2OH

OHO

HO

OF

C

CH3

CH2OCO(CH2)3CH3

OCO(CH2)3CH3O

Intermediate

Isopropyl Ether

HO

OF

C

CH3

CH2OH

OCO(CH2)3CH3O

Betamethasone Valerate Manufacturing Process: -

1. Clean & check the entire machine used for production in all respect before use. 2. Charge Methylene Chloride at RT 3. Charge Betamethasone Base at RT 4. Heat up to reflux.


5. Addition of Tri Ethyl Ortho Propionate 6. Addn. of PTSA 7. Addn. of Ethyl Acetate 8. Reflux the Rx. Mixture at 55 ºC 9. Cool the Rx. Mixture at 25 ºC 10. Then add Orthophosphoric Acid 11. And the Rx. Mixture at 25 ºC 12. Filtration & Washing with 13. Charging of Acetone 14. Filtration & Washing with Acetone 15. Charging of Acetone 16. Wet cake quenching in DM water & strring. 17. Drying, In process testing (B.M.P.) 18. Charging of pyridine. 19. Charging of B.M.P. (Dry) & cooling 20. Addn. of Methane Sulphonyl Chloride. 21. Rx/Mass quinch in Ice+ D.M. Water 22. Filtration and washing with DM water, in process testing (Mesylate) 23. Charging of Methylene Chloride 24. Add Mesylate 25. Concentration organic layer 26. Add. Di-Methyl Formamide & heating 27. Add. Lithium Chloride & stirring 28. Check T.L.C. 29. Rx/Mass Quinch in Ice + D.M. Water 30. Filtration & washing with D.M. Water, in process testing (Clobetasol Crude) 31. Charging of chloroform 32. Add. Clobetasol Crude 33. Add. Methanol 34. Stirring (Check Clarity) 35. Add Activated Carbon and filter it over hyflowbed 36. Collect organic layer and heat up to 600 C 37. Conc. Up to thick mass 38. Filtration and washing with Methanol 39. Drying under vacuum, in process testing (Clobetasol Propionate ) 40. Final Quality Control sampling to be done for complete analysis. 41. Release the material after obtaining test results from Quality Control. 42. Packed in specified containers with proper label.


2.3 CHEMICAL REACTION SEQUENCE OF BETAMETHASONE SODIUM PHOSPHATE Stage: 1st

Stage: 2nd


1. Clean & check the entire machine used for production in all respect before use. 2. Charging of T.H.F 3. Charging of Dexamethasone (Base) 4. Cool it up to -50 C 5. Add. Of Pyro Phosphoryl Chloride 6. Stirring 7. Rx / mass quenched in ice + water 8. Stirring


9. Charge Rx / mass in glass flask 10. Heating 11. Recover T.H.F. / concentration U /Vacuum 12. Stirring 13. Filtration 14. Washing with D.M. Water 15. Drying 16. Cleaning and checking in Glass flask 17. Charging of Thinner / Methanol 18. Add. D.H.P. 19. Heating and Stirring 20. Add. Activated Carbon and then stirring 21. Filtration over hyflowbed 22. Collect filtrate in glass flask 23. Add. of NaOH 24. Stirring 25. Addition of Isopropyl Alcohol 26. Add. of Acetone 27. Stirring 28. Filtration and wash with acetone 29. Drying 30. Final Quality Control sampling to be done for complete analysis. 31. Packed in specified containers with proper label

2.4. CHEMICAL REACTION SEQUENCE OF CLOBETASOL PROPIONATE Stage: 1st


Stage: 2nd

Stage: 3rd


Stage: 4th

MANUFACTURING PROCESS OF CLOBETASOL PROPIONATE: Stage 1st: Betamethasone to Betamethasone -17-propionate. Betamethasone is reacted with Tri-ethylorthopropionate in presence of Dichloromethane. A reaction mass of Betamethasone-17-propionate (1st Intermediate) under reflux is obtained. Wet cake is separated by removal of solvent and addition of water. The wet cake is dried for next step at 500C to 550C. Stage 2nd: Betamethasone -17-propionate to propionate -21-Mesylate ester. Betamethasone -17-propionate is reacted with methane sulfonyl Chloride in presence of pyridine as solvent to get Betamethasone -17 –propionate -21- mesylate ester (2nd intermediate). The wet cake is separated by addition of water. The wet cake is dried for next step at 500C to 550C. Stage 3rd: Betamethasone -17-propionate-21-Mesylate ester to Clobetasol Propionate. Betamethasone -17-propionate -21-mesylate este. (2nd Intermediate) is reacted with Magnesium Chloride in presence of Di methyl formamide to get Clobetasol crude which is recrystallised in Chloroform and methanol mixture pure wet cake of Clobetasol -17 – propionate is obtained after carbon treatment. The wet cake is dried at 500C to 550C. Finally powder of Clobetasol -17 –propionate is milled and sieved. STAGE 4TH : PURIFICATION RAW MATERIAL USED:

a) Methanol & Dichloromethane b) Clobetasol Propionate (Crude) c) Activated Charcoal


Process: Clean the equipment & get it dry. Charge required quantity of Methanol & Dichloromethane in to the flask then charge crude Clobetasol Propionate with continuous stirring and get it complete dissolve into the solvent at room temperature now charge activated charcoal and stir for 15 min. Transfer the filtrate into another distillation flask & distilled out solvent under vacuum. Quinch consented mass into D.M. Water with continuous slow stirring with in one hour at room temperature then filter and wash D.M. Water. The wet material is to be dried for half an hour under vacuum and unload wet material for further drying. Drying : Charge filter mass into SS Trays containing butter paper. Dry it first in air at 600 C for 2 hrs. and again dry at 800 C for 2 hrs. than finally dry at 1000 C for 2 hrs. Send the sample for moisture content, Identification & TLC test confirming it in should be with in limit then cool the mass up to RT & unload it double polythene bags. Milling / Micronising : Pass total material through pulveriser containing required size of the mesh as per party’s requirement. Final analysis : Inform to QC Deptt. For complete analysis of sample of Clobetasol Propionate as per BP. PACKING : After approving the materials get it pack into required size of container. Container should be water proof, heat resistant and light resistant. Label, approved slip from QC Dept. & material handing precaution slip should pasted on the container before dispatching. 2.5. CHEMICAL REACTION SEQUENCE OF DEXAMETHASONE SODIUM PHOSPHATE REACTION Stage: 1st


Stage: 2nd

Manufacturing Process:

1. Clean & check the entire machine used for production in all respect before use. 2. Charging of T.H.F 3. Charging of Dexamethasone (Base) 4. Cool it up to -50 C 5. Add. Of Pyro Phosphoryl Chloride 6. Stirring 7. Rx / mass quenched in ice + water 8. Stirring 9. Charge Rx / mass in glass flask 10. Heating 11. Recover T.H.F. / concentration U /Vacuum 12. Stirring 13. Filtration 14. Washing with D.M. Water 15. Drying 16. Cleaning and checking in Glass flask 17. Charging of Thinner / Methanol 18. Add. D.H.P. 19. Heating and Stirring 20. Add. Activated Carbon and then stirring 21. Filtration over hyflowbed 22. Collect filtrate in glass flask 23. Add. of NaOH 24. Stirring


25. Addition of Isopropyl Alcohol 26. Add. of Acetone 27. Stirring 28. Filtration and wash with acetone 29. Drying 30. Final Quality Control sampling to be done for complete analysis. 31. Packed in specified containers with proper label

2.6. CHEMICAL REACTION SEQUENCE OF DEFLAZACORT Stage: 1st

Stage: 2nd


1. Charging of Methanol in glass flask at RT 2. Heat up to clear solution 3. Cleaning of glass flask


4. Connecting of nitrogen gas cylinder 5. Charging of 21 beta methyl ,17 nitro, 3,20- dione, 1,4 pregnadiene

6. Addition of above solution at 50C to 100C

7. Stirring for 2 hours at 50C to 100C 8. Check TLC if ok 9. Addition of Acidic Water solution

10. Stirring for 2 hours 50C to 100C 11. Filtration and slurry washing with DM Water 12. Drying of Deflazacort crude in oven 13. Charging of Acetone in glass flask at RT 14. Charging of Methanol in glass flask at RT 15. Charging of Potassium Acetate in glass flask at RT 16. Charging of Glacial acetic acid in glass flask at RT 17. Charging of Deflazacort crude 18. Heat up to reflux 19. Reflux for 3 hours at 65 to 700C: 20. Check TLC if ok 21. Addition of Activated carbon 22. Stirring for 1 hour 23. Filtration over hyflow bed prepaid in Methanol 24. Concentration of filtrate up to thick mass 25. Cooling up to 10 0C 26. Filtration and washing with Methanol 27. Drying in oven 28. QC Sampling for complete analysis.

2.7. CHEMICAL REACTION SEQUENCE OF BUDESONIDE Stage: 1st


Stage: 2nd

Process:

2.8 CHEMICAL REACTION SEQUENCE OF PREDNISOLONE SODIUM PHOSPHATE Stage: 1st


Stage: 2nd

Process:

2.9. CHEMICAL REACTION SEQUENCE OF PREDNISOLONE ACETATE Stage: 1st


Stage: 2nd

Process:

2.10. CHEMICAL REACTION SEQUENCE OF MOMETASONE FOURATE Stage: 1st

Stage: 2nd


Stage: 3rd

Stage: 4th

Process:

2.11. CHEMICAL REACTION SEQUENCE OF METHYLPREDNISOLONE ACETATE Stage: 1st


Stage: 2nd

Stage: 3rd

Process:


3. HORMONES 3.1. CHEMICAL REACTION SEQUENCE OF TESTOSTERONE Stage: 1st

Stage: 2nd

Stage: 3rd Crude (Testosterone) purifies in absolute alcohol and water.


Process: 1 mole 4-Androstene-3,17-dione reacts with 1 mole Triethyl orthoformate in the solvent media which gives 1 mole of this Step-I (3-Ethoxyandrosta-3,5-dien-17-one) with the by-product 1 mole Ethyl formate and 1 mole Ethanol. 1 mole Step-I reacts with 1 mole Sodium borohydride and 1 mole Methanol and then reacts with 1 mole Hydrochloric acid with 1 mole Water in the solvent media which gives 1 mole of this Step-Crude (Testosterone) with the by-product 1 mole Sodium ethoxide, 1 mole Boron trihydride (gas), 1 mole Methanol and 1 mole Hydrochloric acid.

2. CHEMICAL REACTION SEQUENCE OF NANDROLONE

19NOR=1 KgTriethylorthoformate= 0.2 KgMethanol=3 KgPyridine Hydrochloride=0.10 KgPyridine =1.1 Kg

Filtration

ML TO ETP

Drying

Dry Stage Ist =1.1 Kg

Reaction

PROCESS FLOW DIAGRAM OF NANDROLONE DECANOATE

N-Filter

Dryer


DMWater

Isopropylalcohol=6 KgSodiumborohydride=0.20 KgAcetic Acid=0.15 KgMethylene Chloride=4 KgCaustic Soda=0.25 Kg

ML TO ETP

Dry Stage 2ND=1.0 Kg

Reaction

N-Filter

Dryer


Acetic Acid

Hexane=5 KgDecanyl Chloride=1.1 Kg

Methanol=4 KgSdium Carbonate=1 KgCaustic Soda=0.2 Kg

ML FOR RECOVERY

Dry NANDROLONE DECANOATE0.80 Kg

Reaction

N-Filter

Dryer

Dry Nandrolone Decanoate

Hexane=8 KgAlumina=6 KgHyflow=0.25 KgCarbon=.15 Kg

Dry NANDROLONE DECANOATE PURE0.60 Kg

Purification

N-Filter

Dryer


3. CHEMICAL REACTION SEQUENCE OF NORETHISTERONE

19 Nor =5 Kg1,4-dioxane= 80 Kg

Potassium tertiary butoxide=5 Kg

Reaction Mass Quenching

DMWater200 L

Filtration

DMWater Washing

DMWater Washing ML to ETP

Drying

Dry NORETHISTERONE (Crude)=5.1 Kg

Reaction

Reaction Mass in DMWater

PROCESS FLOW DIAGRAM OF NORETHISTERONE

Dryer

N-Filter


3.1 Solvent Management System

• All the products will be purified in their respective solvent to remove impurities. •Solvents will be collected and sold off to authorized re-processor for distillation of mixed solvent or will be distilled in the proposed solvent distillation system. •The reactors will be connected to an efficient condenser system with cooling/chilling water/brine circulation. •Reactor and solvent handling pumps will have mechanical seals to prevent leakages. Also provide with breather valve to prevent losses. •Solvent will be taken from storage tank to reactors through closed pipe line. Storage tank will be vented through trap receiver and condenser operated on cooling water. • The condensers will be provided with sufficient HTA and residence time so as to any loss of solvent. • Proper earthing will be provided wherever solvent handling is done.

• Entire plant is flame proof. • Solvents will be stored as per statutory requirement.

• Solvents will be kept at a separate specified area with all the safety measures.

Norethisterone (Crude) 5.1 KgAluminium Oxide=40 KgCarbon=.250 Kg

Filtration

Acetone Washing ML for Distillation Acetone=40 KgToluene=20 Kg

Drying

4.8 KgDRY (PURE) NORETHISTERONE

Purification

N-Filter

Dryer


Fig:5 Solvent Recovery System 5.3 Power Requirement The power requirement will be 40 HP. The power will be supplied from Rajasthan Rajya Vidyut Vitran Nigam Limited. 5.4 Water Supply Water Requirement will be 1200 litres/day. The water will be supplied by RIICO water connection. 5.5 Man Power Requirment During operational phase total manpower will be 25. Local people will be the same will be sourced from the nearby areas.

Table-5 Manpower Distribution S.No. Categories Number

1 Manager/Accountant 1 2 Supervisor 1 3 Skilled labour 3 4 Semi Skilled Labour 5 5 Unskilled Helper 15

Total 25 5.6 Land break-up

Table-6 Land break-up S.No Land Area (m2)

1 Green area 165 2 Roof top area 235


3 Paved area 100 Total 500

6.0 SITE ANALYSIS

(i) Connectivity The project unit is located at H1-174 RIICO, Shree Khatushyam Ji Industrial Area, Reengus, District-Sikar, Rajasthan. The said area is notified by RIICO and it is adjoining with Reengus and Sargoth. Location wise, the site is well connected with Gurgaon through NH-11 and SH-28 and SH-37C. There are lots of organized and un-organized manufacturer situated in these area. The availability of raw materials and marketing of finished goods will be no problem for proposed industry. (ii) Climate and Rainfall The mean annual rainfall (1971-2011) of the district is 463.0 mm whereas normal rainfall (1901- 70) is lower than average rainfall and placed at 459.8. Almost 95% of the total annual rainfall is received during the southwest monsoon, which enters the district in the last week of June and lasts upto the middle of September. The climatology data of Sikar district is presented in Figure 6.

Fig: 6 Climate and Rainfall

The mean annual rainfall is highest (536.6 mm) in Neem Ka Thana, which is located in the south eastern part of the district. It is lowest in Fatehpur (407.8 mm), which lies near north western boundary of the district. The climate of the district is generally dry except during the monsoon period. The humidity is highest in month of August with mean daily relative humidity of 80%. (iii) Geomorphology and Drainage

Geomorphologically, the district comprises the following geomorphological units (Figure7):


Hilly area in the east, undulating area in the centre with hillocks, western desertic plain (major part of the villages and plains are sandy with development of dunes to the north of Sikar).

Fig: 7 Geomorphology and Drainage The hilly tract is part of the Aravalli range. A chain of hills passing through Sakarai Mata Ji lying east of Sikar divides the district almost into two east & west halves. The western part represents typical desertic topography. The altitude of the highest peak is about 1052 m amsl and that of other hills generally ranges between 350 and 700 m amsl. The plain area generally lies at altitude between 380 and 530 m amsl. The terrain in the north-west slopes towards west. The hill peaks which have attained considerable height in the hill system of the district are at Raghunathgarh, Harsh, Deogarh and Shyamgarh, all falling in Sikar tehsil. The central portion of the district can be called as watershed with the rivers and streams in the north flowing towards north, those in the south towards south and those in the east towards east. There is no perennial river in the district. The most important rivers in the district are Mendha, Kantli, Dohan, Krishnawati and Sabi. Mendha river flowing in Danta Ramgarh and Sri Madhopur tehsils merges with the Sambhar lake. Kantli originates near Khandela in Sri Madhopur tehsil and flows out of the district in the northeasterly direction to district Jhunjhunu. Dohan River flows in the uppermost northeastern region of the district and covers a small portion of it. Krishnawati river originates from the hills in the southeast of Neem Ka Thana and flows out of the district in the northeastern direction. Sabi River flows only in Neem Ka Thana tehsil. In the western desertic plain, there is practically no surface drainage system. Apart from these, there


are several minor streams or nallahs originating from the hills which flow for short distances and disappear in the sandy tract. There is natural lake near Pritampuri in the eastern part of the district. It is a small depression where rainwater accumulates and lasts for a few months. Similarly, there are no big tanks in the district. However, small tanks or pits are numerous in the area.

(iv) Hydrogeology The availability, occurrence and movement of ground water is mainly controlled by the topographic features, physical characteristics and structural features present in the geological formations. Ground water occurs under unconfined to semi-confined condition. The principal aquifer in the area is Quaternary sediments covering major part of the district (resting in western and central parts of the district) whereas quartzite, schist, phyllite, limestone and dolomitic limestone of Delhi Super Group also constitute important aquifers (resting in the eastern and north central parts of the district mainly in Neem ka Thana, Khandela, Danta Ramgarh and part of Piprali blocks). Ground water occurs in the pore spaces and interstitial openings of Quaternary alluvium while in hard rock formations, occurrence and movement of ground water is controlled by secondary porosity i.e. through the bedding planes, fissures, joints, fractures, solution cavities and other structurally weaker planes. Hydrogeological map of the area is depicted in figure 3. Exploratory drilling done in the district by GSI and CGWB under UNDP Project has revealed the extension of aquifer both in lateral and vertical directions.

Fig: 8 Hydrogeology of Sikar


7.0 Social Infrastructure available (1) Education:- Sikar has become a major education hub of Rajasthan these days. Along with numerous government colleges providing arts, sciences, and commerce education, a number of private educational institutes have also opened up. Shri Kalyan Government College is the largest college . sikar University has been opened in 2013 by Rajasthan Govt. In the last few years many coaching institutes have become established in the city for the preparation of JEE, PMT, AIIMS and other competitive exams. The coaching class movement started in the early 'nineties but grew modestly because of a lack of quality providers. However, in recent years, the city has become a force to reckon with due to multiple high quality institutions like Matrix JEE Academy for IIT JEE and GCI and CLC for PMT preparation. Those students who follow coaching institutes no longer migrate to other major cities, like Kota and Jaipur. (2) Road and Rail:- Sikar Junction railway station comes within the territory of the North Western Railway. Sikar city is connected through a 1,000 mm (3 ft 3 3⁄8 in) meter gauge railway line section to Jaipur, and a broadgauge line to Jhunjhunu, Rewari, and Delhi and Sikar - Churu rail line began converting to 5 ft 6 in (1,676 mm) broad gauge. Railway Minister Suresh Prabhu on 1 September 2015 (Tuesday) flagged off two trains to mark the completion of Rs. 260 crore gauge conversion of the 122 km Loharu-Sikar railway line in Rajasthan. Both trains were flagged off by Prabhu through remote control by organising video conferencing between Rail Bhawan in New Delhi and Sikar. Prabhu pointed out that sufficient funds have been provided in 2015-16 to complete this project, i.e., Jaipur-Ringas-Churu by March, 2017. Rail service between Sikar and Delhi as train no.14811/14812 Sikar - Delhi Sarai Rohilla Express (bi-weekly) began 2 September 2015. This train was inaugurated by Suresh Prabhu as well as more trains from Sikar to Delhi and for rest of India has been demanded by public. Sikar is well connected by roads from all the major cities of Rajasthan and nearby states. A four-lane national highway NH-11 passes through the center of the city. NH-11 connects Sikar with Jaipur and Bikaner. The western freight corridor will also pass through Sikar, as a main project of the central government. Kotputali Kuchaman Mega Highway also passes through Sikar. The nearest airport to Sikar city is Jaipur International Airport, which operates daily flights to Delhi, Mumbai, Hyderabad, Bangalore, Pune, Indore, Ahmedabad, Chennai, Guwahati, Kolkata, Udaipur, Dubai, Sharjah, Muscat. A new airport is proposed at Shahpura (a town in Jaipur district) that is very near to Sikar. A small air strip at Tarpura village is also available for the landing of small private planes (against payment). (3) Proposed infrastructure Industrial Area (processing area) It is an industrial land and the location is ideal for the marketing point of view of finished goods and raw materials for manufacturing of such types of Synthetic organic chemicals.

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

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

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

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

https://en.wikipedia.org/wiki/Kota,_Rajasthan


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

https://en.wikipedia.org/wiki/North_Western_Railway_Zone_(India)



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


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

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

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

https://en.wikipedia.org/w/index.php?title=Sikar_-_Churu_rail_line&action=edit&redlink=1

https://en.wikipedia.org/w/index.php?title=Sikar_-_Churu_rail_line&action=edit&redlink=1

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

https://en.wikipedia.org/wiki/5_ft_6_in_gauge_railway

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

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

https://en.wikipedia.org/w/index.php?title=Rs._260_crore_gauge_conversion&action=edit&redlink=1

https://en.wikipedia.org/w/index.php?title=Loharu-Sikar_railway_line&action=edit&redlink=1

https://en.wikipedia.org/w/index.php?title=Loharu-Sikar_railway_line&action=edit&redlink=1


https://en.wikipedia.org/w/index.php?title=Rail_Bhawan&action=edit&redlink=1

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


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

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

https://en.wikipedia.org/wiki/Sikar_-_Delhi_Sarai_Rohilla_Express

https://en.wikipedia.org/wiki/Sikar_-_Delhi_Sarai_Rohilla_Express

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



https://en.wikipedia.org/wiki/National_Highway_11_(India)


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

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


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

https://en.wikipedia.org/wiki/Hyderabad,_Andhra_Pradesh

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

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

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

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

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

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

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

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

https://en.wikipedia.org/wiki/Sharjah_(city)

https://en.wikipedia.org/wiki/Muscat,_Oman

https://en.wikipedia.org/wiki/Shahpura,_Jaipur_District




https://en.wikipedia.org/w/index.php?title=Tarpura&action=edit&redlink=1


Residential Area (Non processing area) Residential colony is not proposed for proposed project. The local labor will be preferred to provide employment opportunities. Green Belt Greenbelt will be developed in 33% of the total area of the proposed project. Social Infrastructure Proposed project will result in growth of the surrounding areas by increased direct and indirect employment opportunities in the region including ancillary development and supporting infrastructure. Connectivity The project is well connected with Rail and Road and Airport. Industrial Waste management The proposed plant would be based on “ZERO EFFLUENT DISCHARGE”. 8.0 REHABILITATION AND RESETTLEMENT (R & R) PLAN No Rehabilitation and Resettlement plan is applicable because there are no Rehabilitation & Resettlement of the people. 9.0 Project Schedule and Cost Estimates The project will start only after obtaining Environmental Clearance and all other required clearance and will complete after two years of commencement. The Capital Cost of the project is Rs is 140Lakh 10.0 WASTE MANAGEMENT 10.1 Liquid Effluent According to the nature and quantity of generated effluent, an Effluent Treatment Plant of 7 KLD capacity will be enough to treat the overall generated wastewater quantum due to the proposed manufacturing unit. 10.2 Solid Waste Solid waste estimated to be generated in the proposed industry is in the form of ETP sludge, and municipal solid waste. The waste generated will be temporarily stored in the form of covered room inside factory premises at cooled and dry place. Boiler Ash will be used for land filling purposes of Low Lying Area whereas ETP sludge will be disposed through authorized TSDF facility CETP Seetapur, Jaipur.

Table-8 Types and Quantity of Solid Waste Particulars Proposed Management ETP sludge 25Kg/month ETP sludge will be transfer to

CETP, Seetapur, Jaipur. Municipal Solid waste 10-12kg/month Authorised recycler


10.3 Air Pollution Industry will have only one D.G. set with stack of height 32 meter. So there will be no air emissions in the due to the proposed project.

10.4 Noise Pollution Control:

There is no danger of noise pollution from plant. The green belt will (plantation of dense trees across the boundary) help in reducing noise levels in proposed plant as a result of attenuation of noise generated due to plant operations, and transportation. Earmuffs would be used while running the equipments of the plant. D.G sets are provided with acoustic to control the noise level within the prescribed

limit. A high standard of maintenance will be practiced for plant machinery and equipments,

which helps to avert potential noise problems.

11.0 GREEN BELT DEVELOPMENT/ PLANTATION Green belt development in and around the project site helps in to attenuate the pollution level. About 165 square meter (33%) land area of project will be developed as green belt and it will be maintained in future also. Green belt will be developed as per Central Pollution Control Board (CPCB) Norms. The Avenue plantation will give priority to native species, and the periphery will be devoted to generation of green belt area. 12.0 CSR Activities Proposed project will result in growth of the surrounding areas by increased direct and indirect employment opportunities in the region including ancillary development and supporting infrastructure. Special emphasis on Financial and Social benefits will be given to the local people including tribal population, if any, in the area. Development of social amenities will be in the form of medical facilities, education to underprivileged and creation of self help groups. No adverse effect on environment is envisaged as proper mitigation measures will be taken up for the same.

Documents

Form-1 and PRE FEASIBILITY REPORTenvironmentclearance.nic.in/writereaddata/FormB/TOR/PFR/...M/s Ratantray Pharmaceuticals Pvt Ltd Proposed manufacturing plant for Vitamins, Steroids