ANNEXURE - environmentclearance.nic.in · M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala,...
Transcript of ANNEXURE - environmentclearance.nic.in · M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala,...
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
ANNEXURE – A
DETAILS OF PRODUCTS
Sr. No. Name of Product Production[ MT/Month]
1 Chlomiphene Citrate 1
2 Oxyclozanide 15
3 Bupropione hydrochloride 5
4 Benfotiamine 1
5 n-butyl bromide And / OR
Iso propyl bromide And / OR
n-propyl bromide
306
7
8 Chlorzoxazone 10
9 Piroxicam 5
10 Nitrazepam And / OR
Diazepam10
11
12 Buclazine dihydrochloride And / OR
Meclazine dihydrochloride10
13
14 Tramadol hydrochloride 5
15 Duloxetine hydrochloride 5
16 Dapoxetine hydrochloride 5
17 Lidocaine hydrochloride 5
18 Sodium Bromide solution 5
TOTAL 112
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
ANNEXURE – B
DETAILS OF RAW MATERIALS CONSUMPTION
Sr.no.
Name of Raw Materials Consumption(MT/Month)
Chlomiphene Citrate 11 P-Hydroxy Benzo Phenone (PHBP) 0.53
2 DEC HCl 0.55
3 BTAC 0.04
4 MDC 1.85
5 Water 1.06
6 NaOH 0.26
7 Benzyl chloride 0.79
8 Mg Turning 0.16
9 2-Me THF 4.23
10 DIl. HCl 0.26
11 IPA 2.65
12 Con. H2SO4 0.21
13 Chloroform 3.97
14 Cl2 gas 0.13
15 Sodium Carbonate 0.95
16 Citric acid 0.35
17 Methyl Ethyl Ketone 2.91
Oxyclozanide 15
1 2,4-DCP 6.24
2 Dil.HNO3 (60%) 4.80
3 Na2S 7.38
4 Water 7.92
5 H2SO4 2.79
6 MCB 55.20
7 TCSA 9.18
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8 Thionyl chloride 4.54
9 Acetone/Methanol 45.96
10 Activated carbon 0.615
Bupropione HCl 5
1 3-chloropropiophenone 3.33
2 NBS 3.93
3 PTSA 0.04
4 MDC 9.00
5 Water 3.33
6 Tert. butylamine 4.33
7 IPA 10.00
8 IPA. HCl 3.66
Benfotiamine 1
1 Thiamine Hydrochloride 0.74
2 Phosphoric Acid 0.52
3 TBA 0.96
4 Chloroform 1.67
5 Water 1.64
6 Caustic flakes 0.21
7 Benzoyl chloride 0.11
8 Con. HCl 0.16
9 Mysol 0.83
N-Butyl Bromide 30
1 N-Butanol 18.2
2 HBr/Liq.Bromine 20.0
3 H2SO4 0.45
ISO-Propyl Bromide 30
1 N-propanol 17.2
2 HBr/Liq.Bromine 19.5
3 H2SO4 0.85
N-Propyl Bromide 30
1 N-propanol 17.15
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
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2 HBr/Liq.Bromine 19.50
3 H2SO4 0.85
Chlorzoxazone 10
1 4- Chloro-2-aminophenol 10.00
2 Urea 8.32
3 HCl 5.62
4 Methanol (80%) 12.50
5 MDC 5.00
6 Carbon 0.25
Piroxicam 5
1 Methyl Benzothiazine iso propyl ester 4.52 2 Amino pyridine 1.42
3 O-xylene 31.82
4 IPA 22.73
5 Carbon 0.37
Nitrazepam 10
1 Chloroacetyl chloride 4.67
2 2-amino 5-nitro benzophenone 10.08
3 Toluene 41.67
4 Ammonia 2.08
5 Methanol 52.08
6 Carbon 0.42
Diazepam 10
1 Chloroacetyl chloride 4.61
2 (5-chloro-2-methylamino)phenyl)(phenyl)methanone
10.08
3 Toluene 41.15
4 Ammonia 2.10
5 Methanol 51.44
6 Carbon 0.41
Buclazine dihydrochloride 10
1 P-chloro benzhydrylpiperizine 6.36
2 P-tert butylbenzyl chloride 4.04
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
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3 NaOH 0.89
4 Toluene 22.22
5 Acetone 17.78
6 Carbon 0.22
7 HCl 1.56
Meclazine dihydrochloride 10
1 P-chloro benzhydrylpiperizine 6.98
2 meta methylbenzylchloride 3.41
3 NaOH 0.98
4 Toluene 24.39
5 Acetone 19.51
6 Carbon 0.24
7 HCl 1.71
Tramadol hydrochloride 5
1 Cyclohexanone 1.81
2 Formaldehyde 0.56
3 Dimethylamine 0.83
4 m-chloroanisol 2.63
5 Mg Turning 0.445
6 Toluene/THF 20.37
7 Acetone 18.52
8 Carbon 0.28
9 HCl gas 0.67
Duloxetine hydrochloride 5
1 2-acetyl thiophene 2.10
2 Formaldehyde 0.50
3 Dimethylamine 0.75
4 Toluene 8.33
5 Methanol 13.33
6 Ni cat. 0.03
7 DMSO 10.00
8 Fluro naphthalene 2.42
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
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9 KOH 1.87
10 Acetone 16.67
11 HCl gas 0.6
Dapoxetine hydrochloride 5
1 3-chloro-1-phenylpropan-1-one 2.51
2 Methanol 11.94
3 Ni cat. 0.07
4 Alpha naphthol 2.15
5 KOH 0.84
6 Toluene 11.94
7 Methane sufonicacid 1.43
8 Diethylamine 0.67
9 Acetone 17.91
10 Carbon 0.15
11 HCl gas 0.54
Lidocaine Hydrochloride 5
1 2,6-Xylidine 2.28
2 Chloro acetyl chloride 2.11
3 Diethyl amine 1.38
4 NaOH 0.75
5 Toluene 20.75
6 Acetone 15.09
7 Carbon 0.19
8 HCl 1.32
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
ANNEXURE – C
DETAILS OF MANUFACTURING PROCESS
1. Clomiphene Citrate
Process:
STAGE‐I: KETO OIL FORMATION: Methylene chloride, BTAC, PHBP, Diethyl Amino Ethyl Chloride HCl, Sodium
Hydroxide and D.M. water are reacted in reaction vessel at specific temp. andtime and at different interval of time of reaction steps.
Product in oil form is obtained after layer separation and reaction is carriedout.
After layer separation collected organic MDC is distilled out.STAGE‐II: CARBINOL FORMATION (GR) 2‐Methyl THF and Magnesium Turning are charged and stirred. Benzyl chloride is added and steam is applied. After reflux cool the mass. Keto‐Oil and 2‐ Methyl THF are added. Cooling is applied and mass is stirred. Mass is allowed to settle. Reaction mass is heated and 2‐Methyl THF is distilled out. Cooling is applied and IPA is added. Mass is filtered and centrifuged. Mother liquor is separated out.
STAGE‐III: HYDROLYSIS Carbinol and C.H2SO4 and Chloroform are added. Mixture is stirred. Mixture is used with chloroform for next step.
STAGE‐IV: CHLORINATION Mixture is cooled and liq. Chlorine is added. Mass is stirred. Sodium carbonate is added to the mass and it is stirred. Mass is allowed to settled. Layers are separated out. In lower organic layer water is added. Steam is applied and chloroform is distilled out.
STAGE‐V: CITRATE FORMATION Clomiphene base, MEK and Citric acid are added under stirring. Rection mass is cooled, stirred and filtered by centrifugation. Mother liquor is separated and product is dried.
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
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Chemical Reaction:
(4-hydroxyphenyl)(phenyl)methanoneMolecular Weight: 198.22
O
OH
(4-(2-(diethylamino)ethoxy)phenyl)(phenyl)methanoneMolecular Weight: 297.39
O
ON
ClN . HCl
Molecular Weight: 172.10
2-chloro-N,N-diethylethanamine
(Keto Oil)
Molecular Weight: 297.39
O
ON
1-(4-(2-(diethylamino)ethoxy)phenyl)-1,2-diphenylethanolMolecular Weight: 389.53
ON
OHCl
Molecular Weight: 126.58
Mg-turning
Keto Oil(Carbinol)
ON
OH
(Carbinol)
Acid catalyst ON
(E)-2-(4-(1,2-diphenylvinyl)phenoxy)-N,N-diethylethanamine
Molecular Weight: 371.51
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
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ON
(Z)-2-(4-(2-chloro-1,2-diphenylvinyl)phenoxy)-N,N-diethylethanamineMolecular Weight: 405.96
ON
(E)-2-(4-(1,2-diphenylvinyl)phenoxy)-N,N-diethylethanamine
Molecular Weight: 371.51
Cl
chloriation
ON
Cl
(Z)-2-(4-(2-chloro-1,2-diphenylvinyl)phenoxy)-N,N-
diethylethanamine
citric acid
ON
Cl .
HO
OOH
O OH
O
HO
(Z)-2-(4-(2-chloro-1,2-diphenylvinyl)phenoxy)-N,N-diethylethanamine 2-hydroxypropane-1,2,3-tricarboxylate
Molecular Weight: 598.08
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
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Mass Balance:
Keto oil
Hydro Product
Input : 884.05 Kg Output : 884.05 Kg
Carbinol
Clomiphene base
PHBP : 20 KgDEC HCl : 21 KgBTAC : 1.6 KgMDC : 70 LWater : 40 LNaOH : 10 Kg
Reaction vessel
Waste water : 67.6 KgMDC : 68.5 LSolvent loss : 1.5 Kg
Seperation &solvent
distillation
Benzyl chloride : 30 KgMg Turning : 6 Kg2-Me THF : 160 LWater : 60 KgDil. HCl : 10 kgIPA : 100 L
IPA reco : 95 LWaste water : 106.2 KgSolvent loss : 10 L2-Me THF : 155 L
Seperation &Solvent
Distillation &Centrifuge
Hydrolysis
Chloroform : 145 LWaste water : 74.6 Kg
Chlorination,Distilation and
Centrifuge
Pulvarising andPacking
Con. H2SO4 : 8 KgChloroform : 150 L
Cl2 gas : 4.95 KgSod. Carbonate : 36 KgWater : 33 L
Citric acid : 13.5 KgMEK : 110 L
Chlorination,Distilation and
Centrifuge
MEK : 106 LEvaporation loss : 6.7 Kg
Clomiphene citrate (37.8 kg)
Drying Loss : 10.15
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
2. Oxyclozanide
Process:
STEP ‐I: Nitration Reaction: Dilute nitric acid is charged and Stirred. 2,4-dichlorophenol is added under
cooling. After stirring it is filtered. The wet cake will be used in the next step without drying.
STEP‐II: Reduction Reaction: Water and sodium sulphide are stirred, heated and 2,4-dichloro-6-nitrophenol
is added. After stirring and heating at specific temp. and time MCB and sulphuric acid
are added. MCB layer containing 2,4-dichloro-6-aminophenol will be used in the next
step.Step-III [Crude Oxyclozanide] Mono Chloro Benzene, 3, 5, 6-Trichloro Salicylic Acid and Thionyl chloride are
charged, Scrubber pump is started and products are heated. Thionyl chloride is distilled out. Material is transferred into 2, 4, Di chloro – 6-
Amino phenol and Mono Chloro Benzene. HCl is scrubbed through Scrubber. After reflux, mass is cooled and filtered. Product is dried.
Step-IV [Oxyclozanide] Acetone, Crude Oxyclozanide and Activated Carbon are added Mass is refluxed, heated and stirred. The reaction mass is stirred and filtered in hyflow bed to remove charcoal. Mass is chilled, stirred and filtered. Mass is washed in chilled acetone and dried.
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
Chemical Reaction:
O2N
Cl
OHCl
2,4-dichloro-6-nitrophenol
Molecular Weight: 208.00
H2N
Cl
OHCl
2,4-dichloro-6-aminophenol
Molecular Weight: 178.02
Na2SMolecular Weight: 78.04
OH
OHO
Cl
Cl Cl
3,5,6-trichlorosalicylic acid
SOCl2OH
OCl
Cl
Cl Cl
H2N
Cl
OHCl
+OH
OCl
Cl
Cl Cl
HOO
Cl Cl
Cl
NH
Cl
OHCl
2,3,5-trichloro-N-(3,5-dichloro-2-hydroxyphenyl)-6-hydroxybenzamide
O2N
Cl
OHCl
Cl
OHCl HNO3
+ H2O
2,4-dichlorophenol 2,4-dichloro-6-nitrophenol
water
Molecular Weight: 163.00 Molecular Weight: 208.00
H2O +++ Na2S2O3
H2SO4
Na2SO4 H2O
MW-158 MW-142
++ HCl SO2
2,3,5-trichloro-6-hydroxybenzoyl chlorideMolecular Weight: 259.90
2-amino-4,6-dichlorophenol
Molecular Weight: 259.90
Molecular Weight:178.02
Molecular Weight: 401.46
(Oxyclozanide)
MCB
130 0C
Molecular Weight: 241.46
Molecular Weight: 118.97
63
18
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
Mass Balance:
Oxyclozanide : 250 KgInput : 2410.7 Kg Output : 2410.7 Kg
2,4 - DCNP
2,4 - DCAP
Acid chloride
Oxyclozanide crude
Rec. Acetone/Methanol :730 LSolvent loss : 20 LResidue : 16 Kg
2,4-DCP : 104 KgDil.HNO3(60%) : 80 KgMCB : 100 L
Reaction vessel
Waste water : 70 KgMCB reco : 95 LLoss : 5 L
Nitration &Filtration
Na2S : 123 KgWater : 132 LH2SO4 : 43.5 KgMCB : 410 L
Waste water : 160 LReduction
SO2 gas : 40.75 KgHCl : 46.5 Kg
Chlorination
MCB reco : 780 LDistilled residue : 15 KgEvaporation loss : 25 LWaste water : 100.5 L
Condensation,Centrifuge and
Distillation
Chilling and Centrifuge
TCSA :153.5 KgThionyl chloride : 75.75 KgMCB :410 L
Acetone/Methanol :766 LActivated carbon :10 Kg
Filter Spent carbon : 10 Kg
Drying Loss : 47
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
3. Bupropione Hydrochloride
Process:
Step‐I: Preparation of 2-bromo-1-(3-chlorophenyl)propan-1-one: 3‐Chloropropiophenone ,PTSA are charged and stirred. NBS is charged and
mass is heated. After cooling MDC and DM water are charged. Mass is stirred and organic layers are separated out.
Step‐II: Preparation of 2-(tert-butylamino)-1-(3-chlorophenyl)propan-1-one In organic layer tert. Butyl amine is charged and product is heated to reflux. DM water is charged. Layers are separated and aqueous layer is extracted with MDC. Both Organic layers are distilled out under vacuum. Product is obtained as
Oil.Step‐III: Preparation of Bupropion hydrochloride: IPA is added in Base oil. Mass is cooled and IPA,HCl is added in it. Mass is hold, filtered and washed with chilled IPA. Mass is dried under vaccum.
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
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Chemical Reaction:
Cl
CH3
O
1-(3-chlorophenyl)propan-1-one
Molecular Weight: 168.62
Cl
CH3
O
Br
2-bromo-1-(3-chlorophenyl)propan-1-one
Molecular Weight: 416.14
NBS
Cl
CH3
O
Br
2-bromo-1-(3-chlorophenyl)propan-1-one
Molecular Weight: 247.52
Cl
CH3
O
HN
2-(ter t-butylamino)-1-(3-chlorophenyl)propan-1-one
Molecular Weight: 239.74
Tert.butylamine
Cl
CH3
O
HN
2-(tert -butylamino)-1-(3-chlorophenyl)propan-1-one
Molecular Weight: 239.74
IPA.HCl
Cl
CH3
O
HNHCl
2-(tert -butylamino)-1-(3-chlorophenyl)propan-1-onehydrochloride
Molecular Weight: 276.20
Bupropion Hydrochloride
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
Mass Balance:
Bupropione HCl : 150 Kg
m-chloro-bromo-propiophenone in MDC
Bupropion base
Input : 1129.2 Kg Input : 1129.2 Kg
3-chloropropiophenone:100KgNBS : 118 KgPTSA : 1.2 KgMDC : 200 LWater : 50 L
Reaction vessel
Waste water : 103.2 LBromination &
SolventDistilation
Tert. Butyl Amine : 130 KgMDC : 70 LWater : 50 Kg
MDC : 260 LEvaporation loss : 10 LWaste water : 178 L
Amination &Solvent
Distillation
IPA : 390 LEvaporation loss : 15 LResidue : 5 Kg
CentrifugeIPA : 300 LIPA. HCl : 110 L
Pulvarising andPacking
Drying Loss : 18 L
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
4. Benfotiamine
Process:
Step‐I: Preparation of thiamine monophosphate(TMP): Poly Phosphoric Acid is added at room temperature and it is cooled. Thiamine Hydrochloride is added and it is stirred. Mass is heated, condensed
and water is added at same temp. for hydrolysis of product. Mass is cooled. Tributylamine is added and stirred. Chloroform is added and it is stirred. After stirring reaction mass is allow to settle and aq. and organic layer is
separated out.The aq. Layer distilled out the under vacuum. After centrifugation and drying product is obtained.
Step‐II: Preparation Of Benfotiamine‐Condensation Reaction Thiamine Monophosphate Chloride and water are stirred. After cooling NaOH solution is added. Mass is stirred. Benzoyl Chloride is added and mass is stirred. After completion of reaction
Conc. HCl is added and mass is stirred. After centrifugation Mysol is added in mass and it is heated to reflux. Product is chiiled, stirred and centrifuged. Mysol is taken for distillation and product is dried.
Chemical reaction:
OHNH2
N+
S
N
N
Cl-
H Cl
thiamine hydrochloride
Molecular Weight: 337.27
+ PO
HOOH
OH
phosphoric acid
Molecular Weight: 98.00
NH2
N+
S
N
N
Cl-
PO
O
OH
OH
thiamine monophosphate chloride
Molecular Weight: 380.79
(TMP)
NH2
N+
S
N
N
Cl-
PO
O
OH
OH
thiamine monophosphate chloride
Molecular Weight: 380.79
(TMP)
+O
Clbenzoyl chloride
Aq.NaOH OS
OP
O
OH
HON
O
N
N
NH2
S-[2-{[(4-Amino-2-methylpyrimidin-5-yl)methyl](formyl)amino}-5-(phosphonooxy)pent-2-en-3-yl] benzenecarbothioate
Molecular Weight: 466.45
(Benfotiamine)
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
Mass Balance:
DryingLoss : 32
Benfotiamine : 168 Kg
Thiamine monophosphate chloride
Input : 1148.7 Kg Input : 1148.7 Kg
Pulvarising &Packing
Thiamine Hydrochloride:125KgPoly Phosphoric Acid: 87.5 KgTBA : 161 KgChloroform : 280 KgWater : 125 Kg
Reaction vessel
Couplingreaction
Mysol : 137 KgWaste water : 216.78 LLoss : 3 kgResidue : 5 Kg
Condensation &hydrolysis
Water : 150 KgCaustic flakes : 34.78 KgBenzoyl chloride : 18 KgCon. HCl : 27.5 KgMysol : 140 kg
Waste water : 300 KgChloroform : 270 KgLoss : 10 KgResidue : 7 Kg
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
5. N-Butyl Bromide
Process:
N-Butanol, HBr/Liq.Bromine and H2SO4 are processed and N-butyl bromide isobtained.
Chemical reaction:
CH3-(CH2)3-OH + HBr + H2SO4 CH3-(CH2)3-Br + H2O
Mass Balance:
Reaction &Distillation
N-Butanol : 1.0HBr/Liq.Bromine : 1.100H2SO4 : 0.025
Waste water : 0.225Losses : 0.250
Input : 2.125 Kg Output : 2.125 KgN-Butyl Bromide : 1.65 Kg
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
6. Iso-propyl Bromide
Process:
N-propanol, HBr/Liq.Bromine and H2SO4 are processed and Iso-propylbromide is obtained.
Chemical reaction:
Mass Balance:
CH3-CH-CH3 + HBr / Br2 + H2SO4
OH
CH3-CH-CH3 + H2O
Br
Reaction &Distillation
N-propanol : 1.0HBr/Liq.Bromine : 1.14H2SO4 : 0.050
Waste water : 0.19Losses : 0.25
Input : 2.19 Kg Output : 2.19 KgIso-propyl Bromide : 1.75Kg
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
7. N-Propyl Bromide
Process:
N-propanol, HBr/Liq.Bromine and H2SO4 are processed and N-propyl bromideis obtained.
Chemical reaction:
Mass Balance:
CH3-(CH2)2-OH + HBr / Br2 + H2SO4 CH3-(CH2)2-Br + H2O
N-Propyl Bromide : 1.75Kg
Reaction &distillation
N-propanol 1.0HBr/Liq.Bromine 1.14H2SO4 0.050
Waste water 0.410Losses 0.250
Input : 2.19 Kg Output : 2.19 KgKg
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
8. Chloroxazone
Process:
4 –CAP and HCl are charged and stirred. Urea is added and heated forreflux.
After cooling the product it is centrifuged and filtered. Methanol is charged in wet cake and it is stirred. After heating carbon is added. Mass is filtered, centrifuged and dried.
Chemical reaction:
OH
NH2Cl
4-Chloro 2-amino Phenol
143
+H2N
ONH2
urea
60
30% HCl
Cl NH
OO
Chlorzoxazone
169
MeOH
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
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Mass Balance:
Input : 1668 Kg Input : 1668 Kg
Chloroxazone crude
4-CAP : 400 KgUrea : 333 KgHCl : 225 KgMDC : 200 Kg
Reaction vessel
Water effluent : 650 KgCentrifuge
Methanol : 500 KgCarbon : 10 Kg
Solid waste : 10 KgS. S. ReactorReflux and filter
Rec. Methanol : 480 LLoss : 15 LResidue : 5 Kg
Centrifuge /Chilling
Chloroxazone : 400 Kg
Pulvarising andpacking
Drying Loss : 108
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
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9. Piroxicam
Process:
O-xylene , 2 Amino pyridine, Methyl Benzothiazine and ISO propyl ester arecharged and heated.
O-xylene is distilled out by vaccum. IPA is added in wet cake with stirring. It is heated for reflux and after it carbon is added and refluxed. After cooling mass is filtered, centrifuged and dried.
Chemical reaction:
SN
O
O
OH
OO
4-Hydroxy2-methyl-2H-1,2,benzo
thiazine-3-isopropylcarboxylate,1-1-dioxide (ester)
+ NNH2
2-Amino Pyridine
Xylene
SN
OOH
OO
NNH
Piroxicam
+ OH
propan-2-ol
60
331297
94
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
Mass Balance:
O-xylene : 1000 Kg
IPA : 100 Kg
IPA : 100 Kg
Piroxicam Crude
Piroxicam : 330 KgInput : 4016 Kg put : 4016 Kg
Methyl BenzothiazineIsopropylester : 297 Kg
2 Amino pyridine : 94 Kgo-xylene : 1100 Kg
Reaction vessel
o-xylene Rec. : 1998 LSolvent loss : 102 L
Centrifuge
IPA : 1300 KgCarbon : 25 Kg
Solid waste : 25 KgS. S. Reactor
Reflux and Filter
Centrifuge /Chilling
Rec. IPA : 1430 KgLoss : 55Residue : 15 Kg
Pulvarising andpacking
Drying Loss : 61
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
10. Nitrazepam
Process:
5-Nitro 2-Amino Benzophenone ( Nitro amino Ketone) is reacted with chloroacetyl chloride in toluene by refluxing and Nitro chloro intermediate isobtained. HCl generated is scrubbed in the scrubbing system.
After the reaction the mass is cooled and centrifuged. Wet cake is taken fornext step.
Toluene layer is distilled to recover solvent. Wet cake is dissolved in Methanol and Nitro chloro intermediate is obtained. The Nitro chloro intermediate is reacted with ammonia in solvent methanol by
refluxing and cooled and filtered. The resultant filtrate is concentrated 50% torecover solvent (which is recycled).
The concentrated mass is cooled and Nitrazepam crystals are obtained.These crystals are centifuged and pure Nitrazepam is dried.
The mother liquor from the centrifuge is sent for recovery of solvent to recovermethanol. The last portion of solvent distilling is methanolic water which issent as effluent.
The residual mass remaining as undistilled is taken as Haz waste.
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
Chemical reaction:
O
NH2
N+O
O-
5-nitro 2-aminobenzophenone
Cl
OCl+
N
HN
O2N
Oammonia51
TolueneMethanol
Nitrazepam
242112
H2O
18
+
O
NH
N+O
O-
OCl
Nitro chloro intermediate318.5
281
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
Mass Balance:
HCl gas 36 Kg scrubber
Nitrazepam : 240 Kg
Nitrochloro intermediate
Input : 2664 Kg Output : 2664 Kg
Chloroacetylchloride : 112 Kg2-amino 5-Nitrobenzophenone242 KgToluene : 1000 L
Reaction vessel
Rec. Toluene : 955 LSolvent loss : 40 LResidue ; 5 Kg
Centrifuge
Ammonia : 50 KgMethanol : 1250 L
S. S. Reactor
Waste water : 128 LMethanol recovery : 1190 LMethanol loss : 55 LResi. : 5 Kg
Filter-Nutch
Spent carbon : 10 KgS. S. ReactorStir & Filter
Carbon : 10 Kg
Chilling and Centrifuge
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
11. Diazepam
Process:
2-MethylAmino 5-Chloro Benzophenone (Chloro Methylamino Ketone) isreacted with chloro acetyl chloride in toluene to get Di chloro intermediate.
HCl generated is scrubbed in the scrubbing system. After the reaction themass is cooled, centrifuged and product is dried. Mother liquor is sent forrecovery of solvent toluene.
The Di Chloro intermediate is reacted with ammonia in solvent methanol atspecific temp.and cooled to isolate by product Ammonium chloride which isremoved by filtration. The resultant filtrate is concentrated to recover solvent(which is recycled).
The concentrated mass is cooled and centrifuged and the pure Diazepam isdried.
The mother liquor from the centrifuge is sent to recover methanol. The lastportion of solvent is methanolic water which is sent as effluent.
The residual mass as undistilled is taken as Haz waste.
Chemical reaction
O
NH
ClCl
OCl+
N
N
Cl
Oammonia51
TolueneMethanol
Diazepam
245112
H2O18
+
O
N
Cl
OCl
Nitro chloro intermediate322.5
284
(5-chloro-2-(methylamino)phenyl)(phenyl)methanone
2-chloroacetyl chloride
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
Mass Balance:
\
HCl gas 36 Kg Scrubber
Dichloro intermediate
Diazepam : 243kgInput : 2668 Kg Output : 2668 Kg
Chloroacetylchloride : 112 Kg(5-chloro-2-(methylamino)phenyl)(phenyl)methanone :245 KgToluene : 1000 L
Reaction vessel
Rec. Toluene : 960 LSolvent loss : 40 L
Centrifuge
Ammonia : 51 KgMethanol : 1250 L
S. S. Reactor
Waste water : 95 KgMethanol recovery : 1195 LMethanol loss : 55 L
Filter-Nutch
Spent carbon : 10 KgS. S. ReactorStir & FilterCarbon : 10 Kg
Chilling and Centrifuge
Drying Loss : 34
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
12. Buclazine dihydrochloride
Process:
This involves 2 steps:1st step Para chloro benzhydryl piperazine is dissolved in solvent Toluene and reacted
with p-Tertiary buthyl benzyl chloride in presence of base Sodium hydroxide. After the reaction is complete, the mass is cooled and filtered. The clear filtrate concentrated to get Buclazine base as thick liquid. The recovered toluene solvent is purified and reused.
2nd step The Buclazine base is dissolved in Acetone, charcoalised and filtered. The filtrate is treated with HCl gas and the resultant reaction mass is cooled
and dihydrochloride salt of Buclazine base separates out by centrifuging anddried.
The mother liquor is sent for recovery of solvent Acetone which is re used. The residual mass remaining as undistilled is taken as Haz waste.
Chemical reaction:
NNH
Cl
4-Chloro benzhydryl piperazine
+
Cl
4-tbutylbenzyl chloride
NaOH
Toluene
40
286 182
NN
Cl
Buclizine Base
NaCl H2O
++58 1
8
Step-1
Step-2
NN
Cl
Buclizine Base
NN
Cl .2HCl
Buclizine dihydrochloride
432
432505
Acetone
2HCl
73
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
Mass Balance:
Buclazine dihydrochloride450.0kgs
Input : 2388 Kg Output : 2388 Kg
Drying Loss : 63
Buclazine base
P-chloro benzhydryl piperazine: 286 KgP-tert butyl benzyl chloride :182 KgNaOH : 40 KgToluene :1000 L
Reaction vessel
Waste water : 65 KgFilter
Carbon : 10 KgAcetone : 800 L
Distillation
S. S. Reactor
Spent Carbon : 10 KgS. S. Reactor
Stir & Filter
Chilling and CentrifugeRec. Acetone : 765 LSolvent loss : 30 LResidue : 5 Kg
Toluene : 950 LSolvent loss : 50 L
HCl : 70 Kg
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
13. Meclazine dihydrochloride
Process:
This involves 2 steps:1st step Para chloro benzhydryl piperazine is dissolved in solvent Toluene and reacted
with m-Methyl benyl chloride in presence of base Sodium hydroxide. After the reaction is complete, the mass is cooled and filtered. The filtrate is concentrated to get Meclazine base as thick liquid. The recovered toluene solvent is purified and reused.
2nd step The Meclazine base is dissolved in Acetone, add carbon and filtered. The
clear filtrate is treated with HCl, refluxed and diydrochloride salt of Meclazinebase separates out. This Meclazine dihydrochloride is isolated by centrifugingand dried.
The mother liquor is sent for recovery of solvent which is re used.
Chemical reaction:
NNH
Cl
4-Chloro benzhydryl piperazine
+
Cl
meta methylbenzylchloride
NaOH
Toluene
40
286 140
NN
Cl
Meclizine Base
NaCl H2O++58 18
Step-1
Step-2
NN
Cl
Meclizine Base
NN
Cl .2HCl
Meclizine dihydrochloride
390
390463
Acetone
2HCl
73
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
Mass Balance:
P-chloro benzhydrylpiperizine: 286 Kgmeta methylbenzylchloride: 140 KgNaOH: 40 KgToluene: 1000 L
Reaction vessel
Waste water: 85 LReflux, Coolingand Filter
Carbon : 10 KgAcetone : 800 L
Distillation
S. S. Reactor
Spent carbon :10 KgS. S. ReactorStir & Filter
Chilling and CentrifugeAcetone : 770 LSolvent loss : 30 L
Toluene : 950 LSolvent loss : 50 L
HCl : 70 Kg
Meclazine Base
Meclazine dihydrochloride410.0 Kgs
Input : 2346 Kg Input : 2346 Kg
Drying Loss : 41
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
14. Tramadol HCl
Process:
This involves 3 steps.1st step Cyclohexanone is reacted with Formaldehyde and Dimethylamine in Solvent
Toluene. After the reaction is complete the mass is quenched with water andcooled and Dimethyl amino methyl cyclohexanone crystals obtained. It isisolated by centrifuging and dried.
The Mother liquor is separated and distilled to get pure Toluene which isrecycled.
2nd step 2-Dimethylaminomethyl cyclohexanone is dissolved in Toluene and stirred
with Magnessium filings and treated with solution of Meta bromo anisole inTHF solvent. After it the mass is quenched with water.
Layers were separated and top organic layer is distilled to recover Toluene . The concentrated mass is intermediate Tramadol Base which is immediately
dissolved in Acetone and taken for next step. Both recovered solvents are purified and reused.
3rd step The Tramadol Base in acetone is charcoaled. After filtration and cooling HCl gas is passed and after reaction it is stirred. After centrifuging and drying Tramadol hydrochloride separates out . The mother liquor is sent for recovery of solvent Acetone which is reused.
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
Chemical reaction:
O
cyclohexanone
98
CH2O
formaldehyde
HN
dimethyl amine
Toluene
30 45
O
N
2-((dimethylamino)methyl)cyclohexanone
H2O
water
Step-1
Step-2
O
2-((dimethylamino)methyl)cyclohexanone
+ + +
+
O
Cl
Toluene/THF
Mg
142155
O
OH N
m-chloroanisol Tramadol Base
MgCl+
60
263
Step-3
Acetone
O
OH N
Tramadol Hydrchloride299.5
O
OH N
Tramadol Base263
HCl
36.5.HCl
15518
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
Mass Balance:
Drying Loss : 28
Cyclohexanone : 98 KgFormaldehyde : 30 KgDimethylamine : 45 KgWater : 100 L
Reaction vessel
2-dimethylaminomethylCyclo hexanone
Waste water : 125 KgReflux, Centifuge
& Drying
m-chloroanisol : 142Mg Turning : 24 KgToluene/THF : 1100/30 LWater : 60 Kg
Rec. Toluene : 1075 LLoss : 25 LWaste water : 112 Kg
Seperation &Solvent
Distillation
Spent carbon : 15 KgStirr and Filter
Rec Acetone : 955 LSolvent loss : 45 LCentrifuge
Acetone : 1000 LCarbon : 15 Kg
HCl gas : 36 Kg
Tramadol hydrochloride:270 Kg
Input : 2650 Kg Output : 2650 Kg
Tramadol base
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
15. Duloxetine HCl
Process:
This involves 4 steps:
1st step 2- Acetyl thiophene is mixed with Formaldehyde and Dimethylamine in
Solvent Toluene. The reaction is carried out. After the reaction is complete the mass is quenched with water and Keto
intermediate is formed. This is isolated by centrifuging and solid is dried andtaken for next step.
The Mother liquor containing toluene is sent for recovery of solvent which isreused.
2nd step The keto intermediate is dissolved in Methanol and reduced by hydrogen
using Ni catalyst. The mass is filtered. The filtrate is concentrated and hydroxy intermediate is
obtained which is dissolved in DMSO and taken for 3rd step. The solvent issent for recovery and reuse. The catalyst is used in next step.
3rd step The hydroxy intermediate solution in DMSO is heated and condensed with
Fluoro naphthalene using base KOH so Ether intermediate is obtained afterwork up with water and extraction with Toluene.
4th step The Ether intermediate from above in toluene is reacted with KOH. The mass is worked up with water and organic layer is concentrated by
distillation under vacuum and Duloxetine base is obtained. The recovered toluene is purified and reused. Benzoic acid is recovered. The Duloxetine base is dissolved in Acetone, charcoaled and filtered. The
filtrate is treated with HCl and Duloxetine Hydrochloride is obtained aftercentrifugation and drying.
The mother liquor is sent for recovery of solvent Acetone which is recycled.
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
Chemical reaction:
126
CH2O
formaldehyde
HN
dimethyl amine
Toluene
30 45Keto intermediate
H2O
water
+ + +
+
DMSO
KOH
2
HydrogenHydroxy intermediate
185
183 18
SO
2-Acetyl thiophene
SO
N
3-(dimethylamino)-1-(thiophen-2-yl)propan-1-one
Keto intermediate
+
183
SO
NH2
SOH
N
step-1
step-3Hydroxy intermediate
185
SOH
N
F
1-fluoronaphthalene146
Methanol
Catstep-2
56S
O
N
Ether intermediate311
+ KF + H2O
water
1858
SO
N
Ether intermediate311
Toluene
KOHstep-4
56
SO
HN
Ether intermediate297
Acetone
HCl 36KOCH3+
70
SO
HN
.HCl
DuloxetineHydrochloride
333
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
Mass Balance:
Mass Balance:
Methanol : 765 LSolvent loss : 35 LNi cat. : 2 Kg (recycle)
DMSO : 575 LLoss : 25 L
2-acetyl thiophene : 126 KgFormaldehyde : 30 KgDimethylamine : 45 KgToluene : 500 LWater : 150 L
Reaction vessel
Waste water : 168 KgRec Toluene : 450 LToluene loss : 50 L
Centrifuge
Methanol : 800 LNi cat. : 2 Kg
Filter &Distillation
Heating, Reflux,Condensation
&Distillation
Waste water : 213 LLayer separation
Chilling & Centrifuge
DMSO : 600 LFluro naphthalene: 145 KgKOH : 56 Kg
Toluene : 1000 LWater : 150 L
KOH : 56 Kgwater : 150 L
Reaction, LayerSeparation
& Distillation
Waste water : 210 KgToluene : 960 LLoss : 40 L
Recover acetone : 955 LSolvent loss : 45 L
Acetone : 1000 LHCl gas : 36 Kg
Duloxetine HCl300kg
Keto intermediate
Hydroxy intermediate
Duloxetine base
Input : 4846 Kg Output : 4846 KgKg
Ether intermediate
Drying Loss : 53
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
16. Dapoxetine Hydrochloride
Process:
This involves 3 steps:
1st step 3-Chloro propio phenone is reduced with Hydrogen in presence of Catalyst Ni
in Methanol solvent to get hydroxy intermediate (3-chloro 1- phenyl propanol). After completion of reaction the mass is filtered to remove catalyst (which is
reused), and the clear filtrate is concentrated to recover solvent. Therecovered Methanol is purified and reused.
The mass is quenched with water and solid Hydroxy compound is isolated bycooling and centrifuging. The wet product is taken for next step.
2nd step The Hydroxy intermediate is dissolved in Toluene and Alfa naphthol solid is
added. After heating and cooling, obtained Hydroxy Naphthyl Ether intermediate
mass is cooled and quenched with water. Layers were separated and top organic layer containing the Ether
intermediate which is taken for the next step.3rd step After drying it is treated with Methane sulfonic acid then stirred with Dimethyl
amine. After heating Dapoxetine base is formed. The mass is quenched with water
and top toluene Organic layer is separated. This layer is concentrated bydistillation under vacuum, to get viscous liquid Dapoxetine base.
Recovered solvent toluene is reused. This base is dissolved in acetone and treated with HCl gas, to get Dapoxetine
Hydrochloride. After Stirring, centrifuging and drying product is obtained. The mother liquor is sent for recovering Solvent acetone which is reused.
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
Chemical reaction:
O
Cl
3-chloro-1-phenylpropan-1-one
OH
ClH2
Methanolstep-1
3-chloro-1-phenylpropan-1-ol
168 170
OH
Cl
3-chloro-1-phenylpropan-1-ol170
+
OH
144alpa naphthol
Toluene
KOHstep-2
56 OH
O
Hydroxy NaphthylEther
278
KCl H2O
1874
OH
O
Hydroxy NaphthylEther
278
SO OOH
Methanesulfonic acid
+ Toluenestep-3
HN
dimethylamine
45
N
O
Dapoxetine base
30596
H2SO4 CH498 16
AcetoneHCl 36
N
O
.HCl
Dapoxetine hydrochloride
341
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
Mass Balance:
3-chloro-1-phenylpropan-1-one :168 KgMethanol : 800 LNi cat. : 5 Kg
Reaction, Filterand Distillaton
Waste water : 300 LCentrifuge
Toluene : 800 Lalpha naphthol : 144 KgKOH : 56 KgWater : 300 L
Waste water : 377 LHeating, Cooling
& Layerseparation
Aq. waste : 393 KgToluene : 765 LLoss : 35 L
Reaction & Layerseparation and
Distillation
Methane sufonic Acid : 96 KgDimethylamine : 45 KgWater : 300 L
Spent carbon : 10 KgFilter
Methanol : 760 LLoss : 40 LNi cat. : 5 Kg(recycle)
Carbon : 10 KgAcetone : 1200 L
Dapoxetine HCl : 335 Kg
Chilling & Centrifuge
HydroxyIntermediate
Water : 300 L
Ether Intermediate intoluene
Acetone : 1150 LLoss : 50 LHCl gas : 36 Kg
Dapoxetine base
Input : 4260 Kg Output : 4260 Kg
Drying Loss : 40
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
17. Lidocaine hydrochloride
Process:
This involves 2 steps.1st step 2,6-Xylidine is added. After cooling Chloro acetyl chloride is added and
stirred. After Centrifugation the cake is washed with chilled Toluene and dried it. The recovered solvent is purified and reused.
2nd step In reactor dry Stage-I material, Toluene, and Diethylamine is added. It is
stirred and heated. After completion of reaction Sodium hydroxide solution isadded.
After Centrifugation the product is washed with cold Water. The wet cakewhich is lidocaine base is dried and pulverized.
Lidocaine base is taken in acetone and filtered after addition of carbon. Thendry HCl gas is purged to the reaction mass and it is chilled and filtered.
The mother liquor is sent for recovery of solvent which is re used.
Chemical reaction:
AcetoneHCl 36
.HCl
Lidocaine hydrochloride
270
NH2
Cl
OCl+
O
Cl
HN
2,6-xylidine Chloro acetylchloride
121112
step-1
Toluene
197
+ HCl
36
O
Cl
HN
197
+ NH
diethylamine73
2-chloro-N-(2,6-dimethylphenyl)acetamide
2-chloro-N-(2,6-dimethylphenyl)acetamide step-2
Toluene
O
NHN + NaCl
58
Lidocaine base
234
O
NHN
NaOH
40
+ H2O
18
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat.
Mass Balance:
HCl gas : 36 Kg2,6-xylidine :121 KgChloro acetyl chloride :112 KgToluene :500 L
Reaction vessel
Toluene Recover : 475 LLoss : 25 L
Centrifuge andDrying
Carbon : 10 KgAcetone : 800 L
Centrifuge andDrying
S. S. Reactor
Spent carbon : 10 KgS. S. ReactorStir & Filter
Centrifuge and Chilling
Lidocaine hydrochloride265.0 Kg
Toluene Recover : 575 LSolvent loss : 25 LWaste water : 269 L
Dry HCl gas : 70 Kg
Toluene : 600 Ldiethylamine : 73 KgNaOH : 40 KgWater : 200 L
Acetone recover : 760 LSolvent loss : 40 L
Lidocaine Base
Amide derivatives
Input : 2526 Kg Output : 2526 Kg
Drying Loss : 46
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates ofM/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat
ANNEXURE – D
DETAILS OF WATER CONSUMPTION AND WASTE WATER GENERATION
DETAILS OF WATER CONSUMPTION :
Sr. no. PURPOSE Consumption, KL/day
1. Domestic 1.5
2. Industrial
a. Process 1.7
b. Boiler make up 10.0
c. Cooling make up 3.0
d. Washing water 0.5
e. Any other –ScrubbingGardening
0.20.5
TOTAL [2] 15.9
TOTAL [1+2] 17.4
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates ofM/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat
DETAILS OF WASTE WATER GENERATION :
Sr. no. PURPOSE Generation, KL/day
1. Domestic 1.2
2. Industrial
a. Process 3.4
b. Boiler blow down 0.5
c. Cooling bleed off 0.02
d. Washing water 0.5
e. Any other –ScrubbingGardening
0.20.0
TOTAL [2] 4.62
TOTAL [1+2] 5.82
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates ofM/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat
DETAILS OF EFFLUENT TREATMENT PLANT
For the proposed project, the sources of waste water will be from process,
washing water, scrubbing and Utilities.
The generated waste water will be collected in the collection cum equalization
tank. Then it will be neutralized if required in the neutralizer tank.
Then the neutralized effluent will be filtered and stored in the holding tank.
The neutralized effluent will be sent to Common MEE system after meeting
with the inlet norms.
CollectioncumEqualizationtank
Wastewater
Neutralizertank Filtration Final
holding tank
ETPsludge
CMEE
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates ofM/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat
ANNEXURE – E
DETAILS OF HAZARDOUS WASTE GENERATION AND ITS DISPOSAL
Sr.No.
Name ofHazardous
Waste
Category asper HWM
Rules,2016
Quantity/ year
Mode of Disposal
1. Discarded
containers /
barrels / liners
33.1 5 MT Collection, Storage,
transportation and sold out
to Registered Recyclers.
2. Used Oil 5.1 0.3 MT Collection, Storage,
transportation and sold out
to Registered Recyclers.
3. Spent Solvent 20.2 Max.
300 MT
Recycled and Reused back
in next batch.
4. Distillation
Residue
20.3 Max.
8 MT
Collection, Storage,
transportation and sent to
CHWIF.
5. Inorganic Acid
HCl
B-15 12-15 MT Collection, storage,
transportation and sold out
to the authorized person.
6. ETP sludge 35.3 12 MT Collection, Storage,
transportation and sent to
secured land fill site.
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates of
M/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat
ANNEXURE – F
DETAILS OF AIR POLLUTION CONTROL MEASURES
DETAILS OF FLUE GAS EMISSION
Sr.No.
StackAttached
to
Capacity Name of fuel& its
consumption
StackHeight
Air pollutionControlSystem
Parameters
1. Steamboiler[ 2 nos.]
1 T/hr.[each]
Coal / Agrowaste
@ 0.8 T/hr11 m
Multicyclone, bagfilter followed
by waterscrubber
PM < 150mg/Nm3SO2 < 100 ppmNOx< 50 ppm
2. D. G. set 10 KVA Diesel@ 7.5 L/hr.
6 m --- PM < 150mg/Nm3SO2 < 100 ppmNOx< 50 ppm
DETAILS OF PROCESS GAS EMISSION :
Sr.No.
Stack Attachedto
StackHeight
Air pollution ControlSystem
Parameters
1. Reactors 11 m Water scrubber
followed by Caustic
Scrubber
HCl<20 mg/Nm3
Cl2< 09 mg/Nm3
SO2< 40 mg/Nm3
NOx< 25 mg/Nm3
Annexures to Form – 1 & Pre Feasibility ReportProposed Project for manufacturing of bulk drugs and its intermediates ofM/s Novazeal Lifesciences, Plot no.806,G.I.D.C., Kerala, District: Ahmedabad, Gujarat
ANNEXURE – G
PLANT LAY OUT
GIDC ROAD
Proposed Storage area
Utilityarea
Office
Parking
Proposed
plant area
GreenSpace
ProposedETP area
Proposedhazardous
wastestorage area
OPEN AREA