ANNEXURES 1 PLANT LAYOUT 2 LIST OF PRODUCTS WITH PRODUCTION CAPACITY AND RAW MATERIALS 2A BRIEF MANUFACTRING PROCESS, CHEMICAL REACTION AND MASS BALANCE WITH FLOW DIAGRAM 3 WATER CONSUMPTION AND EFFLUENT GENERATION WITH SEGREGATION OF EFFLUENT STREAMS 4 DETAILS OF PROPOSED EFFLUENT TREATMENT PLANT 5 DETAILS OF HAZARDOUS SOLID WASTE MANAGEMENT AND DISPOSAL 6 DETAILS OF AIR POLLUTION CONTROL MEASURES 7 DETAILS HAZARDOUS CHEMICAL STORAGE FACILITY 8 SOCIO ‐ ECONOMIC IMPACTS 9 PROPOSED TERMS OF REFERENCES
Transcript
ANNEXURES
1 PLANT LAYOUT
2 LIST OF PRODUCTS WITH PRODUCTION CAPACITY AND RAW MATERIALS
2A BRIEF MANUFACTRING PROCESS, CHEMICAL REACTION AND MASS BALANCE WITH FLOW DIAGRAM
3 WATER CONSUMPTION AND EFFLUENT GENERATION WITH SEGREGATION OF EFFLUENT STREAMS
4 DETAILS OF PROPOSED EFFLUENT TREATMENT PLANT
5 DETAILS OF HAZARDOUS SOLID WASTE MANAGEMENT AND DISPOSAL
6 DETAILS OF AIR POLLUTION CONTROL MEASURES
7 DETAILS HAZARDOUS CHEMICAL STORAGE FACILITY
8 SOCIO ‐ ECONOMIC IMPACTS
9 PROPOSED TERMS OF REFERENCES
ANNEXURE: 1 PLANT LAYOUT
N
ANNEXURE: 2 LIST OF PRODUCTS WITH PRODUCTION CAPACITY
S. No. Products Quantity MT/Month
Bulk Drugs 1. Metoclopramide Hydrochloride
50
2. Cetrizine Hydrochloride 3. Ondensetrone Hydrochloride 4. Trifluoperazine Hydrochloride 5. Mebendazole 6. Tolperisone Hydrochloride 7. Loratadine 8. Fenofibrate and its intermediate 9. Telmisartan and its intermediate 10. Nebivolol and its intermediate 11. Atorvastatin 12. Phenyleffrine 13. Ambroxol 14. Diclofenac Sodium 15. Ofloxacin Sub ‐ Total 50 Bulk Drug Intermediates 16. 3‐4 Diamino Benzophenone
35
17. Acetyl Para amino Salicylic Acid 18. 4‐ Acetamido, 2‐ Methoxy, Benzoic Acid Methyl Ester 19. 5‐ Chloro, 4‐ Acetamido 2, Methoxy Benzoic Acid Methyl Ester 20. 4‐ Chloro Benzhydryl Chloride 21. 4‐Chloro Benzhydryl Piperazine 22. Cetrizine Base Sub ‐ Total 35 Grand ‐ Total 85
BRIEF MANUFACTRING PROCESS, CHEMICAL REACTION AND MASS BALANCE WITH FLOW DIAGRAM BULK DRUGS 1. METOCLOPRAMIDE HYDROCHLORIDE Manufacturing Process:
Stage 1: Feed water, KOH & MAP in Stainless Steel Reactor, stir and heat up to 800C under 4 kg pressure with CO2 gas, maintain for 5 hrs. Than cool it at room temperature. Adjust pH 7.0 with HCl and than add acetic anhydride. Heat up to 40 °C & maintain it for 1 hr. Cool to 300C and centrifuge it. Wash with water. Spin, dry and unload wet cake.
Stage 2: Feed wet cake, Acetone, K2CO3, DMS in SS Reactor and reflux for 12 hrs. Than distill out total acetone under vacuum. Charge DM water in reactor and stir for ½ hr. Centrifuge it and wash with water. Spin, dry and unload wet cake.
Stage 3: Charge wet cake & acetic acid in Glass Lined Reactor. Stir it for ½ hr than cool it to 20°C. Purge with Cl2 gas & add water. Centrifuge it & wash with water. Unload wet cake.
Stage 4: Feed wet cake, toluene, N, N‐Di Ethylene Di Amine with stirring heat up to reflux, maintain it for 5 hrs. Cool it to Room Temperature. Add HCl and water than reflux for 1 hr. Cool to room temperature and separate aqueous layer in SSR. Adjust pH 7.0 with Soda Ash and then pH 9.5 with NaOH. Centrifuge it and wash with water. Unload Metoclopramide, dry it.
Stage 5: In GLR charge Metoclopramide base and charge IPA and Water chilled to 20 degree Centigrade then purge HCl gas up to PH 4.0 to 5.0 then centrifuge it and unload material and Dry it.
Chemical Reaction
Material Balance
2. CETRIZINE HYDROCHLORIDE Manufacturing Process: Stage 1: Charge methanol & PCBP in SS reactor. Cool to 200 C than start addition of sodium Borohydride solution. Check clarity after three hrs. If ok than maintain for 10 hrs. Than distill out total methanol. Charge benzene, allow stirring for ½ hr. Transfer RM to GLR. Stage 2: Add Thionyl Chloride slowly at 600 C Temp. Reflux for three hrs. Cool to Room Temperature and add water. Provide stirring and allow it to settle. Separate aqueous layer and collect organic layer in SSR. Stage 3: Charge Piperazine anhydrous and Caustic Soda flakes in organic layer, maintaining temperature up to 400 C for 5 hrs. Check TLC. If it is ok, distilled out benzene (Total). Add toluene & provide stirring for 15 min. Charge 2 –Chloro Ethanol (2‐CE) & Tri Ethyl Amine (TEA) maintaining temperature 80 0C for 10 hrs. Check TLC if OK add water. First separate out Tri Ethyl Amine solution (for TEA Recovery) than distilled out toluene for R.M. (Total). Cool up to 200 C than charge MDC. Mass of 4 ‐ Chloro Benzhydryl Piperazine is obtained as product. Stage 4: Add Di Methyl Formamide (Catalyst), charge Caustic Potash flakes and Sodium Mono Chloro Acetate partly under Temp. 150 C. Maintain for 5 hrs. Add water and provide stirring, allow it to settle and separate aqueous layer (to ETP). Distill out total methylene Di Chloride under vacuum. Add acetone with Stirring for 10 mins. Filter through Sparkler Filter. Cetrizine Base is obtained as product from this stage. Stage 5: At room temperature spurge dry HCl gas up to pH 1.3. Centrifuge the material, and wash with acetone, collect Mother Liquor for recovery. Dry Cetrizine HCl in dryer. Stage 6 (Acetone Recovery): Divert mother liquor from centrifuge to SSR. Adjust pH 5.5 with caustic soda flakes. Distilled out total acetone. Add water for cooling up to 200 C Charge Methylene Di chloride with stirring, allow to settle and separate aqueous layer (to ETP). Take MDC layer for 4th stage in next batch.
Chemical Reaction
Stage - III
Cl
Cl
HC
Para Chloro Benzhydryl Chloride
M.W.: 237.12
+NH
NH
+ NaOH
Cl
HC NHN
p- Chloro Benzhydryl Piperazine
M.W.: 286.79
Piperazine Anhydrous
M.W.: 86.13
Sodium Hydrxide
M.W.: 40.00
Stage - IV
Cl
HC NHN + Cl.CH2.CH2.OH
2 - Chloro Ethanol
M.W.: 80.51
TEA
Cl
HC NN CH2.CH2.OH
M.W.: 330.85
+ NaCl + H2O
M.W: 58.44 M.W: 18.00
+ HCl
M.W.: 36.5
p- Chloro Benzhydryl Piperazine
M.W.: 286.79
Material
Balance
3. ONDA ManufacStage 1: 10% andthrough S Stage 2: 5 hrs. Cerecovery Stage 3 (distilled material sent to E Chemica
ANSENTRON
cturing ProceIn a GLR, ch
d HydrochlorSparkler Filt
In a GLR Colentrifuge th
y.
(IPA Recoveout IPA coand dry it. TP.
l Reaction
E HYDROCH
ess: harge Iso Proric Acid 35%er.
llect filtrate e material.
ery): In a SSmpletely. CRecovered O
HLORIDE
opyl Alcohol %. Check cl
and check itUnload and
R, take ML Charge wateOndansetron
and Ondensarity and ch
ts moisture ad Dry Onden
of centrifuger and cool n Base is us
setron Baseheck for pH
and pH, if oknsentron Hy
ge and add cto room t
ed in Stage
. Heat up to 2, if Ok, fi
k chill up to ydrochloride
caustic to obemperature– I for next
o 800C, add wlter the ma
50 C maintae. Collect M
btain pH 9.0e. Centrifuge
batch and M
water terial
in for ML for
0 and e the ML is
Material
Balance
4. TRIFLUOPERAZINE HYDROCHLORIDE Manufacturing Process: Stage 1: Feed Toluene, 1‐ Bromo 3‐ Chloro Propane and N Methyl Piperazine in SS reactor. Add caustic lye at 500C maintain for 5 hrs. Allow to settle and collect organic layer and aqueous layer (to ETP) separately. Stage 2: Charge Toluene, 2‐ Trifluro Methyl Phenothiazine and Caustic Potash in organic layer obtained from Stage I at 1000C & maintain for 10 hrs. Check TLC or HPLC, if ok add water, stir for 15 min. Allow to settle and separate organic layer. Drain aqueous layer to ETP. Stage 3: Filter Organic layer and divert to GLR and Spurge HCl gas up to pH 1.5. If pH is ok, distill out toluene (total) under vacuum up to 1200C & cool to 500C. Add methyl Iso butyl Ketone. Cool up to room temperature and centrifuge the Material. Unload and dry Trifluoperazine Hydrochloride. Divert ML to SSR for MIBK recovery. Stage 4 (MIBK Recovery): In a SSR, charge ML and distilled out MIBK completely and add Caustic lye solution up to pH 9.00. Charge Toluene & provide stirring for ½ hr. Allow to settle and separate the layers. Aqueous layer is drained to ETP and organic layer is reused in stage – II.
Chemica
l Reaction:
Material
Balance
5. MEBENDAZOLE Manufacturing Process
Stage I (3‐Nitro 4‐Chloro Benzophenone): Feed NCBA, benzene, Thionyl chloride and catalyst Di Methyl Formamide in GLR & heat up to reflux, maintain reflux for 5 hrs, cool down to 20 0C. Start addition of Anhydrous Aluminum Chloride & provide heat up to 35 0C and maintain temperature for 2 hrs. Add water slowly and heat up to 50 0C, allow settling for ½ hr and separate aqueous layer. Due to another wash to organic layer, Benzene (total) is distilled out. Charge water & provide stirring for 15 minute and centrifuge. From centrifuge NCBP is obtained, wash it properly with water. Stage II (3‐Nitro 4‐Amino Benzophenone): In MS Autoclave, charge wet NCBP and NH3 (liq.). Heat up to 130 to 1400C & maintain for 12 hrs. Cool to 350C. Centrifuge it & wash properly. Stage III (3‐4 Diamino Benzophenone): Feed Polysulphide, Stage II product (NABP) and Methanol in SSR. Reflux for 7 hrs & cool to 350C. Add chilled water up to 150C . Centrifuge it & wash it properly with water. The obtained product is DABP. Stage IV (Adduct): Charge water and Thio urea with addition of Di Methyl Sulphite in SSR at 350C & heat up to reflux and maintain reflux for 4 hrs. Cool down to 300C. Add MCF and chilled water to bring down temperature up to 200C. Centrifuge it & wash properly with water. Stage V (Mebendazole): In SSR, charge water, DABP, adduct and acetic acid. Heat up to 600C & maintain temperature for 3 hrs. Add water and heat up to 900C, maintain conditions for 2 hrs. Cool down to temperature 350C. Centrifuge it & wash properly with hot water. Dry the wet mass of Mebendazole.
Chemica
l Reaction
Material Balance
6. TOLPERISONE HYDROCHLORIDE
Manufacturing Process Stage 1: In 20 lit flasks, charge IPA + HCl chilled to 0˚C. Slowly add Piperidine. After addition check pH, it should be acidic. Transfer flask in water bath, add 4‐Me‐propiophenone. Add Paraformaldehyde. Heat to 60‐65˚C slowly. Exothermic reaction takes place. After initial reaction subsides, reflux it for 4 hrs. Distil solvent (IPA) under vacuum. Cool to 50˚C, add acetone. Cool to Room temperature, filter it and wash with acetone. Stage 2: Add solvent to material from stage 1 and heat, clear solution with charcoal. Filter it and wash with solvent. Stage 3: Distil solvent under vacuum. Add fresh acetone, cool to room temperature. Filter it and wash with filtered acetone. Dry wet mass at 60‐70˚C under vacuum. Distil acetone completely and add acetone for washing of wet mass. Wash it and filter it. Dry wet mass. Chemical Reaction
Material Balance
7. LORATADINE AND ITS INTERMEDIATE
Manufacturing Process: M‐5 is reacted with Sulphuric acid and quenched to give M‐6. M‐6 is then chlorinated using Thionyl chloride and AlCl3 catalyst to give M‐7. M‐7 is then reacted with Grignard reagent and then acidified to give M‐8. M‐8 is then acidified and quenched to give Loratidine Crude. The crude is then purified first using Acetonitrile. The product is further purified using Ethyl acetate. Pure Loratidine is obtained by one more purification in Acetonitrile. Chemical Reaction:
Mass Balance:
Sr. No.
Particular Input Qty (kg)
Sr. No.
Particular Output Qty (kg)
1 M‐5 5.8 1 MDC Recovered 154.62 Sulphuric Acid 1.8 2 MDC Loss 6.443 NaOH 6.5 3 THF Recovered 34.844 MDC 161.04 4 THF Loss 1.165 Water 25 5 Chloroform Recovered 59.56 SOCl2 6.63 6 Chloroform Loss 2.87 DMF 0.27 7 Toluene Recovered 57.58 AlCl3 1.45 8 Toluene Loss 1.229 Hyflow 1.26 9 Acetonitrile Recovered 7.5610 Ethylene Dibromide 0.47 10 Acetonitrile Loss 0.3211 THF 36 11 Loratidine 2.0012 Iodine 0.01 12 Effluent to ETP 35.513 HCl 3.1 13 Solid to Incinerator 0.5514 Chloroform 62.3 14 Residue to Incinerator 915 Hexane 4.5 15 Spent Sulphuric Acid 13.116 Toluene 58.72 17 NaHCO3 3.36 18 Acetonitrile 7.88 Total 386.09 Total 386.09
8. FENOFIBRATE AND ITS INTERMEDIATE
4‐Chloro‐4’hydroxy benzophenone is dissolved in acetone and then sodium hydroxide is added. The corresponding sodium phenoxide precipitates and reflux is affected followed by addition of mixture of acetone and chloroform. After reaction completion solvent is distilled from reaction mixture, water is added and acidified. The mother liquor removed from residue by filtration. The residue is dissolved in sodium bicarbonate solution and extracted from ethyl acetate. The aqueous phase is charcoalised and filtered. The filtrate is acidified, filtered and dried to get crude fenofibric acid. The crude fenofibric acid is recrystallized in Isopropanol and filtered followed by Isopropanol washing to get pure fenofibric acid. The fenofibric acid is esterified with Isopropanol using sulfuric acid as catalyst. After product formation reaction mixture is concentrated by Isopropanol distillation up 50 % volume. Reaction mixture filtered and washed with chilled Isopropanol. The wet cake material is taken in methylene dichloride, washed with aqueous sodium bicarbonate solution followed by water wash. The organic layer is charcoalised, filtered and methylene dichloride distilled to get residue. The residue recrystallized in Isopropanol, filters and dried to get Fenofibrate.
Chemical Reaction:
Mass Balance:
Sr. No. Chemical Name Qty. Output Material Kg
1 4‐CHBP 1 Acetone recovery 7.32 Acetone 7.66 Acetone loss 0.363 Caustic soda 1.28 Aqueous Layer 19.924 Chloroform 1.26 Ethyl Acetate layer 11.225 Process water 7.33 CO2 Evaporation Loss 0.196 H2SO4 1.52 Aqueous layer 11.147 Process water 15.62 CF ML 14.568 Activated charcoal 0.11 IPA Recovery 0.719 Sodium bicarbonate 1.2 IPA Loss 0.5410 Ethyl acetate 11.22 Charcoal+Hyflow 0.1311 IPA 17.15 MDC recovery 3.012 Sodium bicarbonate 0.63 MDC Loss 0.0713 Hyflow 0.02 Product 114 MDC 3.07
15 Process water 1.07
Total 70.14 70.14
9. TELMISARTAN AND ITS INTERMEDIATE Manufacturing Process:
4‐Amino‐3‐benzoic acid is esterifies to gives methyl‐4‐amino‐3‐bezoate, which reacted with butryl chloride to produce butyramide derivative, which nitrated with fuming nitric acid to produced nitro derivative, which reduced in presence of Palladium on charcoal and then hydrolyzed to gives Benzimidazole derivative. Benzimidazole is reacted with n‐methyl o‐pheniline Diamine to gives condensed product, which is reacted with bromo ester to gives telmi ester, which hydrolyzed with potassium hydroxide to gives Telmisartan. Chemical Reaction:
CH3
NH2
O
OH
CH3
CH3
O
O
NH2
O
TS-1M wt - 165
CH3OH/H2SO4
65°C
Yield 94 %
CH3
CH3
O
O
NH2
CH3 Cl
O CH3
CH3
O
O
NH CH3
O
CH3
CH3
O
O
NH CH3
OCH3
CH3
O
O
NH CH3
O
NO2
CH3
CH3
O
O
NH CH3
O
NO2
Pd/CharcoalAcetic Acid
CH3
CH3
CH3
O
O
NH
N
CH3
CH3
CH3
O
O
NH
N
CH3
CH3
H
O
O
NH
N
10% NaOH Sol.
Methanol
CH3
CH3
H
O
O
NH
N
CH3
CH3NH
N
N
N
CH3Polyphospheric Acid
NH2
NHCH3
TS-2M wt - 235
TS-3M wt - 280
TS-5M wt - 232
TS-6M wt - 218
TS-7M wt - 304
Fuming HNO3
-20 to -25°C
0 to 5°C
80°C
140 to 145°C
Yield 96 %
Yield 93 %
Yield 86 %
Yield 96 %
TEA/MDC
Mass Balance:
Qty (Kg) Raw material Material Qty(Kg)
3.53 Methanol ML to ETP 7.5741.484 4‐Amino 3‐Methylbenzoic acid
1.314 TEA Recovered MDC+Hexane 6.0841.287 Butryl chloride ML to ETP 7.7050.153 Sodium Bicarbonate 0.387 Sodium Sulphate
12.240 Water 5.094 Hexane
27.675 Total Output 0.90Loss 0.359
Qty (Kg) Raw material Material Qty(Kg)
0.90 TS‐2 ML to ETP 12.7484.050 Fuming Nitric acid 0.090 Sodium Bicarbonate 9.000 DM Water 14.040 Total Output 1.00
Loss 0.292
INPUT OUTPUT
TS‐01
INPUT OUTPUT
TS‐02
INPUT OUTPUT
TS‐03
10. NEBIVOLOL AND ITS INTERMEDIATE Manufacturing Process:
PFA is condensed with Maleic anhydride in presence of AlCl3 and Dichloro ethane solvent to give NB‐1. NB‐1 is then cyclized to give NB‐2. NB‐2 is reduced to NB‐3 using Palladium charcoal catalyst. NB‐3 is reduced using sodium Borohydride to give NB‐4. NB‐4 is reduced to give NB‐5. NB‐5 is epoxydised using dimethyl sulphoxide in presence of MDC to give NB‐6. NB‐6 is condensed with Benzyl Amine in presence of Methanol to give NB‐7. NB‐7 is debenzoylated with Ammonium formate and palladium charcoal to give NB‐8. NB‐8 is then condensed with HCl to give Nebivilol Hydrochloride. Chemical Reaction:
Mass Balance:
Sr. No.
Particular Input Qty (kg)
Sr. No.
Particular Output Qty (kg)
1 Maleic Anhydride 2.8 1 Product 2.002 AlCl3 7.73 2 Effluent to ETP 35.53 EDC 302.38 3 Spent Pd/c 0.74 Para Fluoro Anisole 2.91 4 EDC Recovered 296.35 HCl 6.63 5 EDC Loss 6.086 Hexane 115.84 6 Hexane Recovered 110.517 Acetic Acid 1.7 7 Hexane Loss 5.338 Sulphuric Acid 2.36 8 THF Recovered 109.09 Pd/c 0.82 9 THF Loss 3.5110 Hyflow 1.63 10 MDC Recovered 225.3611 Sodium Borohydride 2.31 11 MDC Loss 6.9812 THF 112.51 12 DMSO Recovered 41.913 MDC 232.34 13 DMSO Loss 1.0914 Sodium Carbonate 1.78 14 Residue 1015 DMSO 42.99 15 HCl 30% 57.0416 Oxahl Chloride 6.54 17 TEA 12.98 18 Sodium Hydride 1.96 19 Methanol 36.05 20 Benzyl Amine 0.66 21 Acetonitrile 16.31 22 Water 30.9 Total 942.13 Total 911.3
11. ATORVASTATIN
MANUFACTURING PROCESS Stage: 1 Preparation of (5R)‐1,1‐Dimethylethyl 6‐Cyano‐5hydroxy 3‐oxo‐hexanoate (ATVS1) (R)‐4Cyano‐3‐hydroxy butyric acid, ethyl ester is reacted with tert butyl acetate in the presence of LDA at low temp to get ATVS1. Stage: 2 Preparation of [R‐(R*, R*)]‐1, 1‐Dimethylethyl 6‐Cyano‐3, 5‐dihydroxy hexonate (ATVS2), ATVS1 is reacted with Sodium Borohydride in THF and MeOH in the presence of Diethyl Methoxy Borane. After completion of reaction, reaction mass is quenched with acetic acid. After work up affords ATVS2. Stage: 3 Preparation of (4R‐Cis)‐1, 1‐Dimethylethyl 6‐Cyanomethyl‐2, 2‐dimethyl‐1, 3‐dioxane‐4‐acetate (ATVS3), ATVS2 is reacted with Acetone in presence of Methane Sulphonic Acid using 2,2‐ Di Methoxy propane. And then it is neutralized with 5% NaHCO3 solution then extracted with Ethyl Acetate. After distillation of Ethyl Acetate MeOH & Water to get ATVS3. Stage: 4 Preparation of (4R‐Cis)‐1,1‐Dimethylethyl 6‐(2‐amino ethyl)‐2,2‐dimethyl‐1, 3‐dioxane‐4‐acetate (ATVS4), ATVS3 is reduced with Methanolic Ammonia in presence of Raney Nickel and Hydrogen gas, then catalyst is filtered off and the filtrate is concentrated to give oily mass ATVS4.
Stage: 5 Preparation of [R‐(R*, R*)]‐2(4‐Fluorophenyl)‐β, 8‐dioxane‐5‐(1‐methylethyl)‐3‐phenyl‐4‐[(phenyl amino)Carbonyl]‐1H‐Pyrrol‐1tert –butyl heptanoic ester (ATV8), ATVS4 is condensed with (+) 4‐fluoro‐α‐2‐methyl‐1‐oxopropyl]χ‐oxo‐N‐β‐ Diphenyl‐benzene butane amide in presence of Pivalic acid using Toluene, Heptane and THF at. After completion of reaction work up is done with 0.1N NaOH & 0.1N HCl. Organic layer is evaporated which is crystallized in IPA and Water to get ATV8.
Stage: 6 Preparation of Atorvastatin Calcium Acidic and basic hydrolysis of ATV8 with HCl and NaOH gives sodium salt of Atorvastatin, which is treated with Aqs Calcium Acetate to give Atorvastatin Calcium in Aqs Methanol.
12. PHENYLEFFRINE Brief process of PHENYLPHERINE HCL STAGE 1: Charge Meta Hydroxyl acetophenone at RT. Charge Ethyl acetate Lot‐1 at RT. Cool to 0 to 2 OC. Charge Aluminium chloride at 0 to 2OC. (note: after Aluminium chloride addition material is not dissolved & after addition of bromine 60 to 70% reaction mass clear solution.) Slowly add bromine solution (bromine is mixed with ethyl acetate LOT‐II) at 0 to 25 OC DURING 2 HRS. (NOTE: then mass solution clear and dark brown colour.) Maintain for 1hr at 0 to 2 OC. Add toluene LOT‐I at 10 to 15 OC. Add D M Water LOT –I at 10 to 15 OC. Stir for 30 min. separate toluene layer and kept aside. Take aq. Layer and charge toluene LOT‐II at RT. Stir for 30min separate toluene and mix with main layer. Take toluene in to reactor add 2%sodium bicarbonate solution. (Note: the toluene layer colour changes to dark brown to greenish colour.) Stir for 30 min. settle for 30 min. separate toluene layer and charge D M Water LOT‐II at RT. Stir for 30 min. settle for 30 min. separate toluene layer and charge D M Water LOT‐III at same temp. Stir for 30min at same temp. Settle for 30 min at same temp. Separate toluene layer and cool to 0 to 2 OC. slowly add 2 Methyl benzyl amine at 0 to 2 OC during 2 hrs. (Note: at the addition starting of n methyl benzyl amine rxn mass changes from greenish to light (yellowish). addition continues then reaction continues then mass colour changes slowly to dark brown.) Maintain for 2Hrs at 0 to 2 OC. Filter the rxn mass and wash with toluene LOT‐II. take clear toluene layer and add Iso Propyl Alcohol HCL solution up to PH comes to 1.0 to 1.5 at 30 to 35 OC. (NOTE: at the time of PH adjustment to IPA HCL material moves like a layer and after PH it forms gummy nature (material struck in walls) . then at the time of maintenance material separate freely.) Stir for 30min at 30 to 35 OC .slowly heat to 50 to 55 OC. Centrifuge and wash with chilled Toluene 100lts .spin dry the material. Unload and dry the material at 50to 55 OC. Finally dry the material at 100 to 105 OC during 30 to 4 hrs for removing of excess HCL gas for smooth reduction Out put: Wet wt: 400 to 410 kg Dry wet: 350 to 360 kg Description: off white to greenish Melting point: 185to 190 OC STAGE 2: charge methanol at RT. CHARGE STAGE –I at RT. Heat to 60 to 65 OC. Check clear solution. Charge carbon at 60 to 65 OC. Stir for 30 min at 60 to 65 OC. Filter the methanol layer through leaf filter and collect filtrate in to a clean and dry autoclave. Wash with methanol LOT‐II through leaf filter. (Take Pd/C and dehydrate with methanol and use in rxn.) Charge Pd/C under nitrogen atmosphere and close manhole. Pass nitrogen gas up to 2 kg pressure and stir for 30 min and degas nitrogen slowly up to 0 Kg pressure. Again pass nitrogen gas up to 2 Kg pressure and stir for 30 min and degas nitrogen slowly up to 0 Kg pressure. Pass hydrogen gas upto 1 kg pressure and stir for 30 min and degas hydrogen slowly up to 0Kg
pressure. Pass hydrogen gas 4.0 Kg pressure at RT. Heat to 50 to 55 OC. Maintain the pressure 4.0 to 6.0 Kg at 50 to 55 OC for 15 to 16hrs. (Note: first 2 hrs consumption is over and maintain the pressure for another rxn because hear two rxn takes place first debenzylation and then further maintenance Ketone reduction.) (Note: at the rxn forwarding the rxn mass is changes to dark brown to pale yellow and material formation in methanol that is the indication of middle stage then you must proceed under hydrogen pressure up to rxn mass color blackish green color. Whenever you stop the middle stages you work out the rxn mass you got the material dark brown and it looks like timber material) Check TLC, if rxn completed. (Note: in TLC first spot moves to upper to middle and then moves to lower. First you check absence of stage –I and further check absence of middle pot. Whenever absence of two spots we can terminate hydrogen gas.) Cool to RT. Degas the hydrogen pressure up to 0 Kg pressure slowly. Pass nitrogen gas up to 2Kg pressure and stir for 30 min and degas nitrogen slowly up to 0 Kg pressure. Again pass nitrogen gas up to 2 Kg pressure and stir for 30min and degas nitrogen slowly up to 0Kg pressure. Filter the Pd/C through leaf filter and collect filtrate in to clean and dry reactor. Wash with 100 Lts methanol to leaf filter. Collect filtrate and distilled of methanol completely under vacuum at below 60 OC up to thick and degas for 2 to 3Hrs. (note: if methanol is present in residue you must loss yield and separation of material is takes time) Residue wt: ‐ 155 to 160 kg. Cool to 40 OC. Charge DM Water‐I at 35 to 40 OC. Stir for 20 min at RT. Check clear solution. PH adjusted to 9.0 to 9.5 with liquor ammonia solution at RT. Stir for 1HR at RT. Cool to 10 to 15 OC. Centrifuge and wash with DM Water LOT_II. Spin dry the material. Unload the material and dry the material at 50 to 55 OC. Out put: Wet wt: 120 to 140 kg Dry wt: 80 to 85 kg Description: brown color solid Melting range: 140 to 145 OC. STAGE‐3: Charge Iso propyl alcohol at RT. charge stage –II at RT. Charge L (+) tartaric acid at RT. Charge DM Water LOT‐I at RT. Heat to 60 to 65 OC .check clear solutions. Stir for 30 min at 60 to 65 OC. Slowly cool to 30 to 35 OC 1 Hr. stir for 5 Hrs at 30 to 35 OC. (note: charge seeding of(+) salt, otherwise salt forms more time (it tales 2 or 3 days) Centrifuge and wash with 15% moisture isopropyl alcohol solution. Inload the salt. Wet wt: ‐ 75 kg (PED (+) salt) Description: ‐ off white powder. Take filtrate MI’s and PH adjusted to 9.0 to 9.5 with liquor ammonia solution. Stir for 30 min at RT. Cool to 10 to 15 OC. Centrifuge and wash with IPA LOT‐II and DM Water LOT‐II solution. Take DM Water LOT‐III at RT. Charge above wet cake at RT. heat to 65 to 71OC. Cool to 25 to 30 OC .stir for 1 Hr to 25 to 30 OC. Cool to 10 to 15 OC. Stir for 1 Hr at 10 to 15 OC. Centrifuge the
material and wash with D M Water LOT‐IV .spin dry the material .Unload the material and dry the material at 55 to 60OC. Output: Wet wt: 50 to 55 KG Dry wt: 35 to 38 Kg Description: off white crystalline powder Melting range: 169 to 172 OC. Optical rotation: ‐ ‐50O STAGE –3: RECOVERY RECOVERY FROM PED (+) SALT: Charge PED (+) salt at RT. Charge DM Water LOT‐I at RT. Heat to 60 to 65 OC .clear solution observed. PH adjusted to 9.0 to 9.5 liquor ammonia solution at RT. Stir for 1Hr at RT. Centrifuge and wash with DM Water LOT‐II. Unload the material and dry the material at 50 to 55 OC. Dry wt: ‐ 45 to 47 Kg, SOR (+) 49O, MR: 140 to 145 OC. Take acetic anhydride at RT. Charge above material at RT during 1 Hr slowly. Slowly add sulphuric acid at 25 to 35 OC during 2 Hrs. heat to 100 to 105 OC. Stir for 1 Hr at 100 to 105 OC. Cool to 80 to 85 OC. Slowly add DM Water LOT‐III at RT. Slowly heat to 85 OC . stir for 3 hrs at 80 to 85 OC. Cool to 40 to 45 OC. Slowly add liquor ammonia 7 Lts at 45 OC. Heat to 75 to 80 OC. distilled of water completely under vacuum at below 80 OC .cool to 40 to 45 OC. Slowly add DM Water LOT‐IV at RT. slowly heat to 85 OC .stir for 3 Hrs at 80 to 85 OC cool to 40 to 45 OC. Slowly add liquor ammonia 13 Lts at 45 OC .heat to 75 to 80 OC. distilled of water completely under vacuum at below 80 OC. cool to 50 to 50 OC. Slowly add D M Water LOT‐IV at RT. Slowly heat to 85 OC. Stir for 3 Hrs at 80 to 85 OC. Cool to 40 to 45OC.slowly add liquor ammonia LOT‐IV up to PH comes 9.0 to 9.5 Lts at 45 OC. Stir for 30 min at rt. Centrifuge the material and wash with DM Water LOT‐V at RT. Spin dry the material. Dry the material at 50 to 55 OC. Dry wt: 35 to 38 KG, SOR (‐) 45o, MR: 169 to 171oC. Take 10 % MC isopropyl alcohol LOT‐I at RT. Charge above dry material at RT. Heat to reflux. Cool to 25 to 30 oC. Centrifuge and wash with 10 % isopropyl alcohol LOT‐I at RT. charge above dry material at RT. Heat to reflux. Stir for 1 Hr at reflux. Cool to 25 to 30 OC. Centrifuge and wash with 10 %IPA LOT‐II. Spin dry the material .dry the material at 50 to 55 OC.
CHEMICA
HOC6H4C
Meta hydacetophe
AL REACTION
COCH3
BR2
droxyl enone
Bro
(C9DL‐EPH
HCL
PHEHC
N
2
omine
9H14ClNO2) ‐PHENYL HERINE
ENYLPHERINL
PD/C MET
METH
NE
CO
C
THANOL
CO
ANOL
OCH2BR
OH
+
OCH2N(CH3)2C6H
OH
2 mam
IPATOL
H5
methyl benzyine
A HCL+ LUENE
yl
MATERIAL BALANCE Sr. No.
MATERIAL BALANCE FOR THE PHENYLEPHERINE HCL
INPUT KG OUTPUT KG 1 3 Hydroxy Acetophenone 162 Ethyl Acetate Recovered 344 2 Ethyl Acetate 356 Ethyl Acetate Loss 12 3 Bromine 70 Toluene Recovered 11204 Toluene 1170 Toluene Loss 505 Sodium Bi Carbonate Solution 16 Methanol Recovered 12006 2‐Methyl Benzyl Amine 263 Methanol Loss 507 IPA HCl 130 IPA Recovered 4058 Methanol 1250 IPA Loss 129 Palladium Charcoal Catalyst 25 Acetone Recovered 23210 Carbon 4.3 Acetone Loss 511 Liq. Ammonia 438 Effluent 115012 IPA 417 Palladium Charcoal Catalyst 2513 L(+)Tartaric Acid 122 ML TO ETP 5236.314 Acetic Anhydride 162 PHENYLPHERINE CRUDE 9015 Sulphuric Acid 33 16 IPA HCl 20% 72 17 Carbon 4 18 Acetone 237 19 DM Water 5000 Total 9931.3 Total 9931.3
13. AMBROXOL Process Description:
1. In a clean dry GLR charge Methanol, Methyl Anthranilate, cool to 15 to 20 OC. Add Bromine maintaining temp at 15‐20 OC, maintain for 2 hrs at 15‐20 OC. Add H2O2 ‐50% maintaining temp 15 ‐20 OC and then for 3.0 Hrs at 15 ‐20 OC , charge water , make PH by Liq. Ammonia 25% to 7.0 to 7.50.
2. In a clean dry SSR Charge THF , Step I and acetic acid , add slowly sodium Borohydride at 15 ‐20 OC within 4‐5 hrs, raise temperature to RT ,
3. Maintain 4 hrs at RT, distill out THF under vacuum max at 70 OC , After distillation completed charge water , cool to RT , Start Centrifuge And give methanol wash for each lot, Spin dry unload & dry in tray dryer.
4. Charge reaction mass from step 3 & Manganese dioxide at RT. Charge EDC, Activated Carbon, Hyflow, Stir for 1.0 Hrs and raise temperature to 95 OC to 110 OC.
5. Start filtration & collect all ML to another SSR, big filtration require, after filtration complete give cake wash toluene , in another SSR , Collect all ML distillate , Toluene under vacuum at 80 OC. Cool to RT , Chill to 15 OC , Maintain 5.0 Hr at 15 OC , Centrifuge , Give methanol wash to material , spin dry , Unload cake and dry in FBD.
6. In clean dry SSR charge Toluene, step 5 under stirring. Charge Trans 4‐Amino Cyclohexanol, reflux at 110 OC. Remove water through distillation, After removing water distill out Toluene atmospherically .Cool to RT. Chill to 10 OC. Centrifuge the mass & wash with Toluene& Spin Dry , unload cake.
7. In Cool dry SS Reactor charge methanol. Charge Step 6 on dry basis .Chill to 10 OC and add Sodium Borohydride at 10 ‐15 OC within 4 Hrs. Raise Temperature to RT for 1.0Hr. Check TLC. If Complies, Raise Temperature Refux 70‐ 80 OC, Maintain for 2.0 Hr. Cool to RT, Chill to 10 OC. Start centrifuge, Spin dry unload cake.
8. In clean dry SS reactor charge Iso propyl Alcohol. Charge Ambroxol Base (Step 5) on dry basis .Heat and reflux. Check clear solution, if ok charge Act. Carbon. Filter Through Sparkler having Hyflow Bed & collect all Ml in GLR. In GLR collect all Ml cool to 5 OC. Add HCL ‐30 % make PH 3.0 to 4.0. After PH Heat to 70 OC & maintain for 1.0 Hr at 70 OC. Cool to RT Chill to 10 OC. Start centrifuge in SS centrifuge. Spin dry unload cake dry in FBD.
ChemicaSTEP‐1
MET
STEP‐2
TETRA HYDROFUN STEP‐3 STEP‐2
A
l Reaction:
THANOL
URASODIHYDR
H+N
ACETONE
METHYLANTHRA
UM BORO RIDE
HCL + NH3
C6H1
L ANILATE
ACETICACID
14O3 M
TRCY
Br2 + NH3 + H2O2
C METHL
MNO2
RANS‐4‐AMIYCLOHEXOL
⇒
STEP‐
STE‐1
HANO
INO
‐1 YEILD
EP
2‐AMINDIBROMDE
⇒
AMB
O‐3,5‐MOBENZALD
BROXOL
DEHY
Material Balance:
SR NO. MATERIAL INPUT
QTY (IN KG)
SR NO. MATERIAL OUTPUT
QTY (IN KG)
1 METHANOL 1900.00 1 RECOVERED METHNAOL 1805.002 METHYL ANTHRANILATE 300.00 2 ML TO ETP 778.003 BROMINE 350.00 3 LOSS METHANOL 95.004 LIQ. AMMONIA 85.00 4 STEP I OUTPUT 570.005 HYDROGEN PEROXIDE 113.00 6 WATER 500.00
TOTAL 3248.00 TOTAL 3248.00 Step 2
1 STEP I 570.00 1 RECOVERED THF 923.002 THF 992.00 2 LOSS THF 69.003 SODIUM BORO HYDRIDE 68.00 3 ML TO 366.004 ACETIC ACID 12.00 4 STEP II OUTPUT 484.005 WATER 200.00
TOTAL 1842.00 TOTAL 1842.00 STEP 3
1 STEP II 484.00 1 RECOVERED TOLUENE 2759.002 TOLUENE 2904.00 2 LOSS TOLUENE 145.003 CHARCOAL 20.00 3 ML TO ETP 200.004 MANGANESE DIOXIDE 1075.00 4 SPENT CARBON 26.005 WATER 200.00 5 STEP III OUTPUT 409.00
6 SOLID WASTE OF MNO2 1144.00 TOTAL 4683.00 TOTAL 4683.00 Step 4
4 TRANS 4‐AMINO CYCLOHEXANOL 160.00 4 STEP IV OUTPUT 591.00
TOTAL 2025.00 TOTAL 2025.00 Step 5
1 STEP IV 591.00 1 RECOVERED IPA 1710.002 IPA 1800.00 2 LOSS IPA 90.003 ACT CARBON 5.00 3 SPENT CARBON 6.004 HCL 135.00 4 OUTPUT STEP V 557.00
5 RESIDUE 168.00 TOTAL 2531.00 TOTAL 2531.00
14. DICLOFENAC SODIUM Process Description
1. Charge 2, 6 DCP, Toluene and Potassium carbonate, heat to 110‐115OC for 2 hrs and remove Toluene. Charge MCA and reflux 4 Hr at temperature 115OC .Charge Aniline and sodium Methoxide solution. Chill to 4‐7OC and centrifuge wash with water and spin dry and unload
2. Charge Reaction mass from Step 1 with Toluene, Sulphuric acid and heat to 75OC, distill out toluene, charge CAC , heat and reflux for 20 Hrs. Chill to 15OC and centrifuge mass.
3. Charge, stage 2 mass and Aluminium chloride and raise temperature to 140OC, stop heating temperature will reach upto 190OC ,then quench in water .Then centrifuge the wet cake in another reactor, charge water and HCL and charge wet cake ,centrifuge the mass and wash with water.
4. Charge stage 3 mass with caustic potash, water, sodium Hydrosulphite and reflux for 8 hrs. Check TLC and then charge another 10 kg extra caustic flake. cool to 25‐30OC
5. Charge Stage 4 mass, DM water, EDTA, Activated Carbon and IPA, heat to 80OC till dissolution, Check pH 10‐13.Charge IPA, Carbon and stir for 30 mins and then filter and centrifuge the mass with chilled wash of IPA.
2,6
(
D
ST
Chemica
STAGE‐12,6DCP(C6H4C
6 Dichloro phen
STAGE‐2
STEP I (DIAMINE)
2,6‐DICHLORPHENYLAMIN
STEP II (N‐CHLOROACE
2,6‐DICHLORPHENYLAMIN
STEP III 1‐(2,6 ‐
ICHLOROPHENINDOLINON
TEP IV (DICLOFSODIUM CRUDE)
l Reaction:
1 l2O)
+
nol
2
) RO NE
+
ETYL, RO NE)
+
NYL) 2‐E)
+
FENAC
+
ANILINE (C6HMETHOXIDE
CHLORO
ALLUMINIUM
SODIUM.H.SUL WATER
IPA CARBON EDTA
MMCA
H5NH2) (CH3NaO)
O ACETYL CHLO
CHLORIDE
LPHITE CAUSTIC
A
TO
(C
SODIUM
RIDE
TO SUAC
C FLAKES
OLUENE
C7H8)
OLUENE ULPHURIC CID
(2,6‐DICH
N‐CHLOROP
(1‐(2,6‐I
STEP IV (
DICLOF
SHLORO PHENY
STEP II
OACETYL, 2,6‐DPHENYLAMINE
STEP III ‐DICHLOROPHEINDOLINONE))
(DICLOFENAC SCRUDE)
FENAC SODIUM
STEP I LAMINE)
DICHLORO E
ENYL) 2‐)
SODIUM
M PURE
Material Balance:
Sr. No.
Particulars
Material Input (in kgs)
Sr. No.
Particulars
Material Output (in kgs)
Stage 1 1 2,6 Dichloro phenol 750 1 ML TO ETP 1770
2 Toluene 1050 2 STAGE I (DIAMINE IN ORGANIC LAYER) 1596
5 Aniline 420 6 Sodium Methoxide Solution 864 WATER 375 TOTAL 4419 4419 Stage II 1 STAGE I (DIAMINE) 1596 1 ML TO ETP 1005 2 Chloro Acetyl Chloride 564 2 STAGE II (ACETYL) 1155 TOTAL 2160 TOTAL 2160
S
O
S
O
15. OFLOProcess D
Stage –I In clean METHANout N‐BuLtrs & dis1/2 hrs adry & un Stage ‐II In clean S4.50, chesparkler methanounload Chemica
STAGE 1
OFLOXACIN Q
STAGE 2
OFLOXACIN CR
OXACIN Description
dry SSR chaNOL, heat to utanol compstil out methat 50 ‐58 oC load cake, M
SSR charge eck for dissofilter all ML
ol solution c
l Reaction fo
ACID + N
P
RUDE IP A
arge OQ ACIreflux 117 o
pletely at lashanol to rem, cool & chi
Ml for IInd cro
1000 Ltrs DMolution, if cL collect in chill to 10 o
or OFLAXAC
‐METHYL IPERAZINE +
CETIC ACID
ID METHANOoC to 125 oCst apply vacumove traces
ll to 0 oC ceop recovery.
M water chalear charge next SSR, In
oC, centrifug
CIN
DI MESULPH
LIQ. AACTVACARBO+D.M.
OL N‐METHC maintain fouum to remof n‐Butanontrifuge the
arge wet cruact carbon,
n a filtrate ge it, Cake w
THYL HOXIDE
MMONIA+ ATED ON+METHANOWATER
YL PIPERAZIor 12‐13 hrs
move all traceol, gain charge mass & cak
ude, Stir & m, heat to 60Ml make Pwash with c
METHAN SODIUMHYDROXFLAKES
OL
INE DI METH check TLC ies of , chargge methanolke give meth
make ph by a0 oC, Stir forH 6.60 to 6chill methan
NOL
M XIDE
OIP
O
HYL SULPHOif complies, ge methanol 500 Ltrs sthanol wash.
acetic acid 4r 1 hr then
6.60 by KOHnol spin dry
OFLOXACIN CRUP
OFLOXACIN
OXIDE Distil
ol 100 tir for . Spin
4.2 to filter
H and y and
UDE
MATERIAL BALANCE
Step 1 Mass Balance Sr No MATERIAL INPUT UNIT STD QTY
Sr No MATERIAL OUTPUT KG
1 OFLOXACIN Q ACID KG 600 1 RECOVERED METHANOL 5762 METHANOL LIT 600 2 OUTPUT STEP 1 7803 N‐METHYL PIPERAZINE KG 250 3 LOSS METHANOL 244 N‐BUTANOL 350 4 N BUTANOL RECOVERED 582 5 LOSS N BUTANOL 18 6 RESIDUAL 70
TOTAL 1800 1800Step 2 SR NO MATERIAL STD QTY OUTPUT KG
1 OFLOXACIN CRUDE IP 780 1 OUTPUT STEP 2 7202 D.M. WATER 3500 2 ML TO ETP 39603 ACTIVATED CARBON 20 3 SPENT CARBON 304 ACETIC ACID 210 5 LIQUOR AMMONIA 200 TOTAL 4710 4710
BULK DRUG INTERMEDIATE
16. 3‐4, DIAMINO BENZOPHENONE
Manufacturing Process: Stage I (3‐ Nitro 4‐Chloro Benzophenone): Feed NCBA, benzene, Thionyl chloride and catalyst Di Methyl Formamide in GLR & heat up to reflux, maintain reflux for 5 hrs, cool down to 20 0C. Start addition of Anhydrous Aluminum Chloride & provide heat up to 35 0C and maintain temperature for 2 hrs. Add water slowly and heat up to 50 0C, allow settling for ½ hr and separate aqueous layer. Due to another wash to organic layer, Benzene (total) is distilled out. Charge water & provide stirring for 15 minute and centrifuge. From centrifuge NCBP is obtained, wash it properly with water. Stage II (3‐Nitro 4‐Amino Benzophenone): In MS Autoclave, charge wet NCBP and NH3 (liq.). Heat up to 130 to 1400C & maintain for 12 hrs. Cool to 350C. Centrifuge it & wash properly. Stage III (3‐4 Diamino Benzophenone): Feed Polysulphide, Stage II product (NABP), Methanol in SSR. Heat up to reflux, maintain reflux for 7 hrs & cool to 350C. Add chilled water up to 150C temperature. Centrifuge it & wash it properly with water. The obtained product is DABP. Chemical Reaction
Material Balance
17. 3‐4, ACETYL PARA AMINO SALICYLIC ACID Manufacturing Process: Feed water, KOH & MAP in SS Reactor, stir and heat up to 800 C under 4 kg pressure with CO2 gas, maintain for 5 hrs. Than cool it at room temperature. Adjust pH 7.0 with HCl than add acetic anhydride. Heat up to 400 C & maintain it for 1 hr. Cool to 30 0C and centrifuge it. Wash with water. Spin, dry and unload wet cake of 3‐4, Acetyl Para Amino Salicylic Acid. Chemical Reaction Material Balance
18. 4‐ AC ManufacStage 1: with CO2
add acetWash wit
Stage 2: total acewash witMethyl E
Chemica
CETAMIDO, 2
cturing ProceFeed water
2 gas, maintatic anhydrideth water. Sp
Feed wet catone under th water. S
Ester.
l Reaction
2‐ METHOXY
ess r, KOH & MAain for 5 hrs.e. Heat up t
pin, dry and u
ake, Acetonevacuum. Chpin, dry an
Y, BENZOIC
AP in SS Rea. Than cool ito 400 C & munload wet c
e, K2CO3, DMarge DM wad unload w
ACID METH
actor, stir anit at room temaintain it fcake.
MS in SS Reaater in reactowet cake of
YL ESTER
nd heat up temperature.for 1 hr. Co
ctor and refor and stir fo4‐Acetamd
to 800 C und. Adjust pH 7ol to 300C a
flux for 12 hor ½ hr. and o, 2‐Methox
der 4 kg pres7.0 with HCland centrifu
rs. than distcentrifuge ixy, Benzoic
ssure than ge it.
il out t and Acid
Material
Balance
19. 5‐ CH ManufacStage 1: with CO2
add acetWash wit
Stage 2: total acewash wit
Stage 3: gas & adAcetamid
Chemica
HLORO, 4‐ AC
cturing ProceFeed water
2 gas, maintatic anhydrideth water. Sp
Feed wet caetone under th water. Spi
In GLR chardd water. Cdo 2, and Me
l Reaction
CETAMIDO 2
ess: r, KOH & MAain for 5 hrs.e. Heat up t
pin, dry and u
ake, Acetonevacuum. Ch
in, dry and u
rge wet cakeCentrifuge iethoxy Benz
2, METHOXY
AP in SS Rea. Than cool io 400 C & munload wet c
e, K2CO3, DMharge DM wunload wet c
e & acetic act & provide
zoic Acid Me
Y BENZOIC A
actor, stir anit at room te
maintain it focake.
MS in SS Reacwater in reaccake.
cid. Stir for ½e water wa
ethyl Ester.
ACID METHY
nd heat up temperature.or 1 hrs.. Co
ctor and refctor and sti
½ hr than coash. Unload
YL ESTER
to 800 C und. Adjust pH 7ool to 300C a
lux for 12 hrr for ½ hr. C
ool it to 200 wet cake
der 4 kg pres7.0 with HCland centrifu
rs. Than distCentrifuge it
C. Purge witof 5‐ Chlor
ssure than ge it.
il out t and
th Cl2 ro, 4‐
Material Balance
20. 4‐ CH Manufac Stage 1: BorohydrThan dist Stage 2: Provide Chloro Be Chemica
HLORO BENZ
cturing Proce
In SS reactoride solutiontill out total
Add Thionylstirring andenzhydryl Ch
l Reaction:
ZHYLDRYL C
ess:
or, charge mn. Check clarmethanol. C
l Chloride slo allow settlhloride.
CHLORIDE
methanol & rity after thrCharge benz
owly at 600 Cling. Separa
PCBP. Cool ree hrs. If okene, allow s
C and reflux te aqueous
to 200 C thk than mainttirring for ½
for three hrlayer and
han start adtain the con hr. Transfer
rs. Cool to Rcollect orga
dition of sodition for 10r RM to GLR
T and add wanic layer of
dium 0 hrs. .
water. f 4 –
Material
Balance
21. 4‐ CH ManufacStage 1: Borohydrout total Stage 2: Provide s Stage 3:temperatprovide s Chemica
HLORO BENZ
cturing ProceIn SS react
ride solutionmethanol. C
Add Thionylstirring and a
: Charge Piture up to 4stirring for 1
l Reaction:
ZHYDRYL PIP
ess: or, charge mn. Check claCharge benz
l Chloride sloallow settlin
perazine an400 C for 5 h5 min. centr
PERAZINE
methanol &rity after th
zene, allow s
owly at 600 Cng. Separate
nhydrous anrs. Check TLrifuge the m
PCBP. Coohree hrs. If ostirring for ½
C and reflux aqueous lay
nd Caustic SLC. If it is ok,ass. ML goe
l to 200 C aok than mai
½ hr. Transfe
for three hryer and colle
Soda flakes , distil out bs to ETP & c
nd start adntain for 10r RM to GLR
rs. Cool to Rect organic la
in organic enzene (Totake packed
dition of so0 hrs. Than dR.
T and add wayer in SSR.
layer; maital). Add waas Product.
dium distill
water.
ntain ter &
Material
Balance
22. CETR
ManufacStage 1: Borohydrout total Stage 2: Provide s Stage 3:temperat& providtemperatAmine sothan cha Stage 4: Chloro Aallow it tunder vaBase is o
Chemica
RIZINE BASE
cturing ProceIn SS reacto
ride solutionmethanol. C
Add Thionylstirring and a
: Charge Piture up to 4e stirring forture upto 8olution (for rge MDC. M
Add Di MetAcetate partlto settle an
acuum. Add btained as p
l Reaction
ess: or, charge mn. Check claCharge benz
l Chloride sloallow settlin
perazine an400 C for 5 hr 15 min. Ch
80 0C for 10 TEA Recove
Mass of 4 ‐ Ch
thyl Formamly under Temd separate acetone. Pro
product.
methanol & rity after th
zene, allow s
owly at 600 Cng. Separate
nhydrous anrs. Check TL
harge 2 –Chlohrs. Check
ry) than dishloro Benzhy
mide (Catalysmp. 150 C. maqueous layovide Stirrin
PCBP. Cool hree hrs. If ostirring for ½
C and reflux aqueous lay
nd Caustic SLC. If it is ok,oro Ethanol TLC, if Ok,
tilled out toydryl Piperaz
st), charge Cmaintain foryer (to ETP).g for 10 min
to 200 C thok than mai
½ hrs. Transfe
for three hryer and colle
Soda flakes , distill out b(2‐CE) & Tri add water.
oluene for Rzine is obtain
Caustic Potar 5 hrs. Add. Distill out n. Filter thro
han start adntain for 10er RM to GL
rs. Cool to Rect organic la
in organic benzene (Tot
Ethyl AmineFirst separ
.M. (Total). ned as prod
ash flakes and water and total Methy
ough Sparkle
dition of so0 hrs. Than dR.
T and add wayer in SSR.
layer; maital). Add tole (TEA). Maiate out Tri Cool up to 2uct.
nd Sodium Mprovide sti
ylene Di Chler Filter. Cetr
dium distill
water.
ntain uene ntain Ethyl 200 C
Mono rring, oride rizine
Material
Balance
ANNEXURE: 3 WATER CONSUMPTION AND EFFLUENT GENERATION Proposed
Sr.
No.
Category Proposed Scenario (m3/day)
Water
Consumption
Waste Water
Generation
1. Industrial
Process 56 50
Boiler 15 1
Cooling 10 1
Washing 12 12
Scrubber 5 5
2. Gardening 2 ‐
3. Domestic 5 4
Total (Industrial) 98 69
Total 105 73
WATER BALANCE DIAGRAM
Raw Water: 105 KL/Day from GIDC
Domestic: 5 KL/Day
Process:‐ 56 KL/Day
Boiler: 15 KL/Day
Cooling Tower:10 KL/Day
Gardening: 2KL/Day
Soak Pit/ Septic Tank: 4 KL/Day
50 KL/Day 1 KL/Day 1 KL/Day
ETP: 69 KL/Day
Washing: 12 KL/Day
Scrubber: 5 KL/Day
12 KL/Day 5 KL/Day
60 KL/Day treated effluent CETP for further treatment
High COD & High TDS: 9 KL/Day MEE
MEE Condensate (8 KL/Day) will be reused in Cooling Tower, Scrubber, Flushing, Boiler and Washing
MEE Salt TSDF
ANNEXURE: 4 ETP DETAILS
M/s. Audi Drugs shall propose an Effluent treatment plant consisting of primary, secondary & tertiary
treatments. The details of ETP are as follows.
1) Raw effluent (60 KL/Day) from plant shall be collected in two nos. Equalization cum
Neutralization Tanks (ENTs) where caustic is added as per requirement from Caustic Dosing Tank
(CDT) as per requirement. Mixers shall be in CETs to keep all suspended solids in suspension and
to provide proper mixing.
2) Then after, neutralize wastewater shall be pumped to Flash Mixer (FM). Alum shall be dosed
from Alum Dosing Tank (ADT) by gravity into FM to carry out coagulation by using a Flash Mixer.
Then poly shall be added from Poly Dosing Tank (PDT). Then effluent is allowed to settle in
Primary Settling Tank (PST).Sludge settle in PST shall be sent to Sludge Sump.
3) Clear supernatant from Primary Clarifier shall be passed in Aeration Tank (AT).Here,
Biodegradation of organic matter of the wastewater shall be carried out by bacteria (suspended
growth) in the AT. The aeration tank provides proper mixing and supplies oxygen to the
microorganisms in the dissolved form through the fine bubble diffusers. A constant feed rate
shall be maintained in the aeration tank. A sludge percentage of around 25 to 30 % by volume
shall be maintained in the aeration tank. Also MLSS and MLVSS ratio shall be maintained to
ensure active microorganism’s growth. Various nutrients like Urea and DAP shall be added from
Nutrient Dosing Tanks (NDTs) regularly so as to ensure proper growth of the microorganisms.
Oxygen shall be supplied by 2 nos. of air blowers (B‐01) through diffusers. Air blowers also keep
MLSS in suspension.
4) Then the overflow of the aeration tank shall be diverted into the Secondary Settling Tank (SST)
for biomass separation. An appropriate retention time is given to the effluent to ensure proper
settling. The sludge settles down into the bottom of the SCL and required amount of settled
sludge shall be recycled back into the aeration tank to maintain desired concentration of
biomass. Excess biomass shall be pumped to sludge sump (SS).Then after, overflow (clear
supernatant) of SCL shall be collected in Treated Water Sump (TWS) before sent to CETP. We
will meet all the norms laid by Gujarat Pollution Control Board.
5) The primary and secondary sludge from the sludge sump shall be pumped to the filter press (FP)
for sludge dewatering. Sludge sump shall be provided with mixers to keep solids in suspension.
The sludge cake from FP shall be collected and packed into the plastic bags and stored in the
HWSA for ultimate disposal to TSDF. The Leachate from the filter press shall be diverted to the
Equalization cum Neutralization Tanks (ENTs) for further treatment.
High COD & High TDS Stream:
1) Raw effluent (9 KL/Day) from plant shall be collected in two nos. Equalization cum
Neutralization Tanks (ENTs) where caustic is added as per requirement from Caustic Dosing Tank
(CDT) as per requirement. Mixers shall be in CETs to keep all suspended solids in suspension and
to provide proper mixing.
2) Then after, neutralize wastewater shall be pumped to Flash Mixer (FM). Alum shall be dosed
from Alum Dosing Tank (ADT) by gravity into FM to carry out coagulation by using a Flash Mixer.
Then poly shall be added from Poly Dosing Tank (PDT). Then effluent is allowed to settle in
Primary Settling Tank (PST).Clear supernatant from Primary Clarifier shall be shall be collected in
ME Feed Tank (MEFT).Sludge settled in PST shall be pumped to Filter Press for dewatering.
Filtrate from FP shall be sent back to ENTs for treatment.
3) Then effluent from MEFT shall be pumped to three stages Multiple Effect Evaporator (MEE).
Condensate from MEE shall be collected in Condensate Storage Tank (CST) before reuse in plant.
Solid from Dryer and Filter Press shall be collected and stored in HWSA for ultimate disposal to
TSDF.
Detail of Units for Effluent Treatment Plant Stream I
Sr. No. Name of Unit Phase I MOC
1 Equalization cum Neutralization Tanks (ENTs) 2 RCC M25 with A/A k. Lining 2 Flash Mixer (FM) 1 RCC M25 3 Primary Settling Tank (PST) 1 RCC M25 4 Aeration Tank (AT) 1 RCC M25 5 Secondary Settling Tank (SST) 1 RCC M25 6 Treated Water Sump (TWS) 1 RCC M25 7 Caustic Dosing Tank (CDT) 1 HDPE 8 Alum Dosing Tank (ADT) 1 HDPE 9 Poly Dosing Tank (PDT) 1 HDPE
Decontamination, Storage & sent to actual recycler.
Distillation Residue
20.3 Process 25 MT/ Month Collection, Storage, Transportation & Disposal to Incinerator site or sent to cement industries for co‐processing
MEE Salt ‐‐ MEE 100 MT/Month Collection, Storage, Transportation & Disposal to TSDF site
Spent Catalyst ‐‐ Process 1.5 MT/Month Collection, Storage, Transportation & Disposal to Incinerator site or return to supplier
Spent Carbon ‐‐ Process 1.0 MT/Month Collection, Storage, Transportation & Disposal to TSDF site or sent to cement industries for co‐processing
MnO2 Sludge ‐‐ Process 25 MT/Month Collection, Storage, Transportation & reuse in next batch
Sodium Sulphate
‐‐ Process 20 MT/Month Collection, Storage, Transportation & Disposal to TSDF site
HCl (32%) D2 Process 200 MT/Month Collection, Storage, Transportation & Sold to end user
Sulphuric Acid (35%)
D2 Process 70 MT/Month Collection, Storage, Transportation & Sold to end user
ANNEXURE: 6 DETAILS OF FLUE & PROCESS GAS EMISSION Flue Gas Emission
1. Details of Flue Gas Stack; Stack Attached To Thermopack Boiler
SOURCES OF GASESOUS EMISSIONS STACK Capacity 5 Lack KCal /Hr Fuel Used Agro waste: 2.5 MT/Day or LDO: 200 Lit/Hr Type of Emissions SO2 NOx SPM Permissible Limits 262 mg/Nm3 94 mg/Nm3 150 mg/Nm3 Stack Height 30 meters Stack Diameter at the Top 600 mm APCM Bag filter + Scrubber
2. Details of Flue Gas Stack; Stack Attached To Steam Boiler
SOURCES OF GASESOUS EMISSIONS STACK Capacity 4 TPH Fuel Used Agro waste: 2.5 MT/Day or LDO: 200 Lit/Hr Type of Emissions SO2 NOx SPM Permissible Limits 262 mg/Nm3 94 mg/Nm3 150 mg/Nm3 Stack Height 30 meters Stack Diameter at the Top 600 mm APCM Bag filter + Scrubber
3. Details of Flue Gas Stack; Stack Attached To D. G. Set
SOURCES OF GASESOUS EMISSIONS STACK
Capacity D.G.Set: 250 KVA Fuel Used HSD: 20 Lit/Hr Type of Emissions SO2 NOx SPM Permissible Limits 262 mg/Nm3 94 mg/Nm3 150 mg/Nm3 Stack Height 11 meters
4. Details of Process Vent ; Vent Attached To Process Sr. No.
The manpower requirement for the proposed project is expected to generate some
permanent jobs and secondary jobs for the operation and maintenance of plant. This
will increase direct / indirect employment opportunities and ancillary business
development to some extent for the local population. This phase is expected to
create a beneficial impact on the local socio‐economic environment.
2) INDUSTRIES
Required raw materials and skilled and unskilled laborers will be utilized maximum
from the local area. The increasing industrial activity will boost the commercial and
economical status of the locality, to some extent.
3) PUBLIC HEALTH
The company regularly examines, inspects and tests its emission from sources to
make sure that the emission is below the permissible limit. Hence, there will not be
any significant change in the status of sanitation and the community health of the
area, as sufficient measures have been taken and proposed under the EMP.
4) TRANSPORTATION AND COMMUNICATION
Since the existing factory is having proper linkage for the transport and
communication, the development of this project will not cause any additional impact.
In brief, as a result of the proposed project there will be no adverse impact on
sanitation, communication and community health, as sufficient measures have been
proposed to be taken under the EMP. The proposed project is not expected to make
any significant change in the existing status of the socio ‐ economic environment of
this region.
ANNEXURE – 9
PROPOSED TERMS OF REFERENCE
1. Project Description • Justification of project. • Promoters and their back ground • Project site location along with site map of 5 km area and site details providing
various industries, surface water bodies, forests etc. • Project cost • Project location and Plant layout. • Water source and utilization including proposed water balance. • Product spectrum (proposed products along with production capacity) and process • List of hazardous chemicals. • Mass balance of each product • Storage and Transportation of raw materials and products.
2. Description of the Environment and Baseline Data Collection • Micrometeorological data for wind speed, direction, temperature, humidity and
rainfall in 5 km area. • Existing environmental status Vis a Vis air, water, noise, soil in 5 km area from the
project site. For SPM, RSPM, SO2, NOx. • Ground water quality at 5 locations within 5 km. • Complete water balance
3. Socio Economic Data • Existing socio‐economic status, land use pattern and infrastructure facilities available
in the study area were surveyed.
4. Impacts Identification And Mitigatory Measures • Identification of impacting activities from the proposed project during construction
and operational phase. • Impact on air and mitigation measures including green belt • Impact on water environment and mitigation measures • Soil pollution source and mitigation measures • Noise generation and control. • Solid waste quantification and disposal.
5. Environmental Management Plan • Details of pollution control measures • Environment management team • Proposed schedule for environmental monitoring including post project
6. Risk Assessment • Objectives and methodology of risk assessment • Details on storage facilities • Process safety, transportation, fire fighting systems, safety features and emergency
capabilities to be adopted. • Identification of hazards • Consequence analysis through occurrence & evaluation of incidents • Disaster Management Plan. 7. Information for Control of Fugitive Emissions
8. Post Project Monitoring Plan for Air, Water, Soil and Noise.
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