Professional Documents
Culture Documents
1. COMPANY PROFILE - 03
2. FACILITIES DESCRIPTION - 06
3. ACTIVE INGREDIENTS - 07
3.1.1. SPECIFICATIONS - 07
3.2.1. NOMENCLATURE - 15
3.3. MANUFACTURE - 17
3.4.2 INTERMEDIATES - 40
Page No. 1
OMEPRAZOLE PELLETS
A) ELEMENTAL ANALYSIS - 47
B) ULTRAVIOLET SPECTRUM - 48
C) INFRARED SPECTRUM - 49
D) NMR SPECTRUM - 50
E) MASS SPECTRUM - 51
4.1 SPECIFICATIONS - 59
5. BATCH ANALYSIS - 61
6. STABILITY STUDIES - 64
8. VENDORS LIST - 76
Page No. 2
OMEPRAZOLE PELLETS
1. COMPANY PROFILE
The Company
The People
Quality
Page No. 3
OMEPRAZOLE PELLETS
Page No. 4
OMEPRAZOLE PELLETS
Administrative Office:
www.metroapi.com
api@metroapi.com
Contact Person
Page No. 5
OMEPRAZOLE PELLETS
2. FACILITIES DESCRIPTION
The production facilities are well designed for handling of materials & machines and
meeting required qualification.
Quality Control
The Q.C. department comprises of in process lab and instrumentation with well
instruments like HPLC, GC etc. It is maintained highly qualified and trained people is a core area
of our plant ensuring that the highest quality products are consistently manufactured.
Production floor
The Production floor consists of S.S. Reactors and Glass Lined Reactors. The area is
provided with proper concealed drainage facility and all process utilities are performed under
protective environment.
Utilities
The utilities include Boiler (Capacity 1000 Kg), Chilling plant (Capacity 2000 ltrs) and DM
Water plant (Capacity 1000 ltrs/hr) and the DM water is generating water, which meets all
required specifications.
Preventive Maintenance is being followed as per schedule for plant & utilities.
Ware house
The plant is having sufficient storage facility for rawmaterials. All solid Rawmaterials are
stored and identified properly. Liquid rawmaterials are stored in storage tanks appropriately.
A regular house keeping schedule with adequate preventive maintenance ensures that
the plant is consistently maintained as per GMP standards.
Page No. 6
OMEPRAZOLE PELLETS
3. ACTIVE INGREDIENTS
3.1.1. SPECIFICATIONS
03 Identification a) The 0.002% soln. In 0.1M NaOH shows two absorption maxima
at 276 nm and 305 nm and ratio is 1.6 to 1.8
b) The IR spectrum concordant with the spectrum of omeprazole
CRS.
c) The spot obtained by TLC the is similar in position and size to
the omeprazole CRS.
Page No. 7
OMEPRAZOLE PELLETS
05 Color of Solution Determine the absorbance of the solution prepared for the
Completeness of solution test at 440 nm, in 1-cm cells, using
methylene chloride as the blank. The absorbance is not greater than
0.10.
Page No. 8
OMEPRAZOLE PELLETS
Page No. 9
OMEPRAZOLE PELLETS
S.No Test Method of Analysis
03. Identification
a) BY U.V The 0.002% of solution in 0.1M NaOH shows two absorption maxima
at 276 nm and 305 nm and ratio is 1.6 to 1.8.
05. Absorbance The absorbance of 2% soln in MDC at 440nm is not more than 0.1
Page No. 10
OMEPRAZOLE PELLETS
S.No Test Method of Analysis
7.1.5 Load 20 µl
07.2. Mobile Phase A mixture of 27 volumes of acetonitrile and 73 volumes of 1.4 g/l.
solution of Disodium hydrogen phosphate previously adjusted pH to
7.6 with phosphoric acid.
07.3. Sample Preparation Weigh accurately about 0.01 gms of sample and dissolve it in 10 ml
of mobile phase.
Page No. 11
OMEPRAZOLE PELLETS
S.No Test Method of Analysis
09. Loss on drying Determined on 1.000 g by drying under high vacuum at 600C for 4 hr.
10. Sulphated Ash Heat a silica or platinum crucible to redness for 10 minutes in muffle
furnace, allow to cool in desiccator and weigh. Put 1 to 2 g. of the
substance, accurately weighed, into the crucible, ignite, gently at first,
until the substance is thoroughly charred. Cool, moisten the residue
with 1 ml. of Sulphuric acid, heat gently until white fumes are no
longer evolved and ignite at 8000 +/- 250 until all black particles have
disappeared. Conduct the ignition in a plate protected form air
currents. Allow the crucible to cool, add a few drops of Sulphuric acid
and heat. Ignite as before, allow to cool and weigh. Repeat the
operation until two successive weighings do not differ by more than
0.5 mg.
Page No. 12
OMEPRAZOLE PELLETS
03 Identification
a) By TLC Determine TLC using Chromatographic Purity Method 1 as per
USP 26 Page 1350.
b) By Infrared Determine Infrared absorption using Method 197K as per USP 26
Absorption Page 2054.
04 Completeness of solution Determine Completeness of solution using Method 641 as per USP
26 Page 2139.
05 Color of Solution Determine the absorbance of the solution prepared for the
Completeness of solution test at 440 nm, in 1-cm cells, using
methylene chloride as the blank.
06 Loss on drying at 600C Determine Loss on drying using Method 731 as per USP 26 Page
for 4 hrs. under vacuum. 2172.
07 Residue on Ignition Determine Residue on Ignition using Method 281 as per USP 26
Page 2061.
08 Heavy Metals
Determine Heavy metals using Method II 231 as per USP 26 page
2057.
09 Organic volatile Determine Organic volatile impurities using Method IV 467 as per
impurities USP 26 Page 2077.
b) Method 2 by HPLC The liquid chromatograph is equipped with a 280 nm detector and
i) Chromatographic a 4.6 mm x 15 cm column that contains 5 m packing L7. The
system flow rate is about 0.8 ml per minute. Chromatograph the System
suitability solution, and record the peak responses as directed
under procedure: the capacity factor, k| , is not less than 6.0, the
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OMEPRAZOLE PELLETS
iii) Phosphate buffer Dissolve 0.725 gm. of Monobasic sodium phosphate and 4.472 gm
of anhydrous dibasic sodium phosphate in 300 ml of water, dilute
with water to 1000 ml, and mix. Dilute 250 ml. of this solution
with water to 1000 ml.
iv) Mobile Phase Prepare a filtered and degassed mixture of Phosphate buffer and
acetonitrile (3:1).
vi) Test solution Inject equal volumes of the Test solution and diluent into the
chromatograph, and allow the Test solution to elute for not less
than two times the retention time of omeprazole. Record the
chromatograms, and measure the peak responses.
Where
ri = The peak response for each impurity
rs = The sum of the responses of all of the peaks.
Page No. 14
OMEPRAZOLE PELLETS
ii) Diluent Prepare a mixture of 0.01 M sodium borate and acetonitrile (3:1)
iii) Phosphate buffer Dissolve 0.725 gm. of Monobasic sodium phosphate and 4.472 gm
of anhydrous dibasic sodium phosphate in 300 ml of water, dilute
with water to 1000 ml, and mix. Dilute 250 ml. of this solution
with water to 1000 ml.
iv) Mobile Phase Prepare a filtered and degassed mixture of Phosphate buffer and
acetonitrile (3:1).
vii) System suitability Dilute a volume of Standard preparation with Diluent to obtain an
solution solution containing about 0.1 mg of USP Omeprazole RS per ml.
viii) Procedure Separately inject equal volumes of the Standard preparation and
the Assay preparation into the chromatograph, record the
chromatograms, and measure the responses for the major peaks.
Where
Page No. 15
OMEPRAZOLE PELLETS
3.2.1 NOMENCLATURE
Compendial Name
Omeprazole.
Chemical Name
5-Methoxy-2-[[(4-methoxy-3,5-dimethylpyridine-2-yl)methyl]Sulfinyl]-1H-
benzimidazole
Page No. 16
OMEPRAZOLE PELLETS
Structural Formula :
OCH3
CH3 CH3 OCH3
N
O
N CH2 S N
H
3.3. MANUFACTURE
Page No. 17
OMEPRAZOLE PELLETS
Stage – II: 4-methoxy 3,5 dimethyl pyridine N-oxide protonised with DMS to give salt of 4-
methoxy 3,5 dimethyl pyridine N-methoxy methosulphate.
Stage – III: Protanated Sulphide salt of 4-methoxy 3,5 dimethyl pyridine N-oxide is rearranged
with Ammonium per Sulphate to give 2-Hydroxy methyl-3,5-Dimethyl-4-methoxy pyridine hydro
sulphate.
Stage – VIII (Purification): Omeprazole technical purified with IPA, MDC, Acetone and
Methanol to give Omeprazole.
After purification, the material dried, tested, pulverised, sifted and packed as per customer
requirements.
Page No. 18
OMEPRAZOLE PELLETS
3,5-Dimethyl-4-
nitropyridine-N-oxide
SMO Stage - I
Stage – II
DMS
2-Hydroxy methyl-3,5-Dimethyl-4-
methoxy pyridine hydro sulphate
2-Hydroxy methyl-3,5-Dimethyl
-4-methoxy pyridine
2-chloromethyl 3,5-dimethyl-4-methoxy-
pyridine hydrochloride
Stage – VI
Page No. 19
OMEPRAZOLE PELLETS
Methanol
Hydrogen peroxide Stage – VII
5-Methoxy-2-[[(4-methoxy-3,5-dimethylpyridine-2-yl)
methyl]Sulfinyl]-1H-benzimidazole Technical
Omeprazole Purified
Packing
Page No. 20
OMEPRAZOLE PELLETS
S.
NAME OF THE EQUIPMENT / MOC CAPACITY LOCATION
NO
01 S.S.Reactor 1600 Ltrs. Production Block
02 S.S Reactor 1600 Ltrs. Production Block
03 Glass lined Reactor 1600 Ltrs. Production Block
04 S.S. Reactor 1200 Ltrs. Production Block
05 Glass lined Reactor 1600 Ltrs. Production Block
06 S.S. Reactor 1000 Ltrs. Production Block
07 S.S. Reactor 800 Ltrs. Production Block
08 S.S. Reactor 1000 Ltrs. Production Block
09 S.S. Reactor 2000 Ltrs. Production Block
10 S.S. Reactor 1000 Ltrs. Production Block
11 S.S. Reactor 2500 Ltrs. Production Block
12 S.S. Reactor (Open Jacket) 300 Ltrs. Production Block
13 S.S. Reactor (Open Jacket) 100 Ltrs. Production Block
14 S.S. Reactor (Open Jacket) 500 Ltrs. Production Block
15 S.S. Reactor (Open Jacket) 500 Ltrs. Production Block
16 Centrifuge 36” Production Block
17 Centrifuge 36” Production Block
18 Ice Brine Pump 2 HP Production Block
19 Centrifuge 36” Production Block
20 Leaf Filter 30 Ltrs. Production Block
21 Leaf Filter 50 Ltrs. Production Block
22 Leaf Filter 100 Ltrs. Production Block
23 Leaf Filter 50 Ltrs. Production Block
24 Leaf Filter 30 Ltrs. Production Block
25 Leaf Filter 50 Ltrs. Production Block
26 Leaf Filter 50 Ltrs. Production Block
27 Water-Demineralization plant 1000 Ltrs/hr Plant
28 Vacuum Pump 5 HP Maintenance
29 Vacuum Pump 5 HP Maintenance
30 Vacuum Pump 5 HP Maintenance
31 Vacuum Pump 5 HP Maintenance
32 Vacuum Pump 5 HP Maintenance
Page No. 21
OMEPRAZOLE PELLETS
Starting materials used in the manufacture are well controlled. Records indicate the
origin date of receipt, date of analysis and date of release by the Quality Assurance Department. All
materials received are checked, sampled, Quarantined tested and release as per the written
specification and standard test procedure.
No material is transferred from the quarantined area or taken into use to any
production process until and unless it is released by quality Assurance. Appropriate status labeling
system is being followed to ensure that only approved material is allowed to production area.
Page No. 22
OMEPRAZOLE PELLETS
03 Identification
06 Related substances
by HPLC
Page No. 23
OMEPRAZOLE PELLETS
02 Solubility Miscible with water, benzene, ether and most of the organic
solvents.
03 Identification
a) Boiling Range Between 64 – 65.5 0C
Page No. 24
OMEPRAZOLE PELLETS
01 Description White sticks, pellets, fused mass or scales strongly alkaline and
corrosive and Hygroscopic material.
03 Identification
a) Test for Sodium A solution (1g in 20 ml) gives the reaction of sodium.
04 Assay by Chemical
a) Total Alkali Not less than 95.0%.
Page No. 25
OMEPRAZOLE PELLETS
03 Identification
Page No. 26
OMEPRAZOLE PELLETS
03 Identification
a) Boiling Range between 59 – 620 C.
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OMEPRAZOLE PELLETS
03 Identification
a) Boiling Range Between 109 – 112 0C
Page No. 28
OMEPRAZOLE PELLETS
Identification by
04 Assay by Chemical Not less than 98.0%.
Page No. 29
OMEPRAZOLE PELLETS
03 Identification by
MB value 304 - 336
Page No. 30
OMEPRAZOLE PELLETS
03 Identification
a) Boiling Range Between 74 – 76 0C
Page No. 31
OMEPRAZOLE PELLETS
03 Identification
a) Melting Range between 2520 C– 2600C
Page No. 32
OMEPRAZOLE PELLETS
03 Identification
a) Boiling Range between 760 – 790C
Page No. 33
OMEPRAZOLE PELLETS
Identification by
03 Assay by Chemical Not less than 80.0%.
Page No. 34
OMEPRAZOLE PELLETS
Identification by
03 pH between 4.0 – 6.0
Page No. 35
OMEPRAZOLE PELLETS
Identification by
03 Boiling Range 860 – 900C
Page No. 36
OMEPRAZOLE PELLETS
Identification by
03 pH (5% solution) between 4.0 – 6.0
Page No. 37
OMEPRAZOLE PELLETS
Specifications Supersedes : Nil Effective from : 01.05.03
01 Description A clear colorless liquid with characteristic odor., chloroform and ether
02 Identification
a) Boiling Range between 54 – 570C
Specifications
Specification No. : MC/RM/S-17 Date of preparation : 21.04.03
Page No. 38
OMEPRAZOLE PELLETS
Identification by
05 Boiling Range 81.00 – 83.50C
Specifications
Specification No. : MC/RM/S-21 Date of preparation : 21.04.03
Page No. 39
OMEPRAZOLE PELLETS
05 Identification by
Boiling Range 38 – 41 0C
3.4.2. INTERMEDIATES
Page No. 40
OMEPRAZOLE PELLETS
List of Intermediates
Page No. 41
OMEPRAZOLE PELLETS
05 Related substances
by HPLC
Page No. 42
OMEPRAZOLE PELLETS
05 Related substances
by HPLC
Page No. 43
OMEPRAZOLE PELLETS
03 Identification
a) by IR or The IR Spectrum is concordant to the spectrum of Standard.
b) by TLC Should be positive
04 Melting Range Between 1180- 120oC
06 Related substances
by HPLC
07 Assay by Chemical Not less than 99% and not more than 101% w/w
(on dry basis)
Page No. 44
OMEPRAZOLE PELLETS
03 Identification
a) by TLC The spot obtained by TLC is similar in position and size to the
standard.
04 Related substances
by HPLC
a) Total impurity Not more than 2.0%
b) Individual Impurity Not more than 1.0%
Page No. 45
OMEPRAZOLE PELLETS
Page No. 46
OMEPRAZOLE PELLETS
Limit
S.No Stage Sample Name Test
(Specifications)
01 Stage –V 2-Hydroxy methyl-4- Related Individual
methoxy-3,5-dimethyl substance by Impurity not
pyridine hydrochloride HPLC more than 2.0%
02 Stage – VI 2-Chloro Methyl 4-Methoxy- Related Individual
3, 5-Dimethyl Pyridine substance by Impurity not
Hydrochloride HPLC more than 1.0%
03 Stage – VII 5-Methoxy-2-[[(4-methoxy- Related Individual
3,5-dimethyl-2-pyridinyl)-2- substance by Impurity not
methyl] thio]-1 H- HPLC more than 1.0%
benzimidazole
04 Stage – VIII 5-Methoxy-2-[[(4-methoxy- Related Individual
3,5-dimethylpyridine-2- substance by Impurity not
yl)methyl]Sulfinyl]-1H- HPLC more than 2.0%
benzimidazole Technical
Page No. 47
OMEPRAZOLE PELLETS
3.5. DEVELOPMENT CHEMISTRY
Structural data
A. ELEMENTAL ANALYSIS:
01 C 59.13 59.41
02 H 5.50 5.75
03 N 12.17 12.05
04 O 13.91 14.15
05 S 9.27 8.62
Page No. 48
OMEPRAZOLE PELLETS
B. ULTRA ---- VIOLET SPECTRUM:
When a 0.002 % w/v solution of Omeprazole in 0.1N NaOH solution was scanned from
200nm to 350nm, two maxima at 306.4 nm and 225.5 nm are obtained as shown in Fig .1. The
peaks absorbances are listed below.
Page No. 49
OMEPRAZOLE PELLETS
OCH3
CH3 CH3 OCH3
N
O
N CH2 S N
H
Frequency cm -1 Assignments
3066.00 N – H stretches
2989.0
2908.0
2808.0 C – H stretches
1629.0
1587.0
1513.0
1467.0 C = C, C = N aromatic rings
1204.0
1157.0 Sp2 – C – O of ethers O- CH3
1079.0
1016.0 Sp3 – C – O of ethers O- CH3
964.0
884.0
824.0 = C – H of the aromatic and pyridine rings
Page No. 50
OMEPRAZOLE PELLETS
D. NMR SPECTRUM
OCH3
CH3 CH3 OCH3
N
O
N CH2 S N
H
5’ CH3 s 2.12 δ
3’ CH3 s 2.21 δ
5 OCH3 s 3.60 δ
4’ – OCH3 s 3.83 δ
S – CH2 s 4.74 δ
7 CH d 7.51 – 7.26 δ
6’ CH s 8.20 δ
E) MASS SPECTRUM
Page No. 51
OMEPRAZOLE PELLETS
OCH3
CH3 CH3 OCH3
N
O
N CH2 S N
H
H
+
CH3O
CH3
CH3O N CH3
+ S
329 (20%) C17H19N3O2S
N N
H
O CH3
+
H3C CH2
CH3O N
+
296 (96%) C17H18N3O2 N
N
H
O
CH3O N
.
+ S+
195 (15%) C8H7N2O2S
N
H
+
O 3HC N
.
C8H8N2OS+ SH
180 (95%)
N
H
Page No. 52
OMEPRAZOLE PELLETS
+O N
.
+ SH
165 (92%) C7H5N2OS
N
H
CH3O
H3C CH3
+
150 (85%) C9H12NO +
H2C N
+
CH3O
.
CH3
+ +
137 (67%) C8H11NO H2C N
OH
3HC CH3
3HC CH3
Conclusion: Based on Elemental Analysis, UV spectrum and IR spectrum, NMR spectrum and Mass
spectrum, it is concluded and conforms the structure of Omeprazole.
Page No. 53
OMEPRAZOLE PELLETS
02. Solubility : Soluble in methelene chloride. Sparingly soluble in Alcohol
and Methanol. Very slightly soluble in water and dissolves
in diluted solutions of Alkali Hydroxides.
04 Particle size : The powder mesh size for commercial requirement is 100
mesh
1) 5-Methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl-2-methyl]thio]-1 H-benzimidazole
( Omeprazole Sulphide)
Page No. 54
OMEPRAZOLE PELLETS
OCH3
CH3 CH3 OCH3
N
N CH2 S N
H
2)5-Methoxy-2-[((4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-sulphinyl]-1 H-benzimidazole-1-
oxide. (Omeprazole N-Oxide )
OCH3
CH3 CH3 OCH3
N
O
N CH2 S N
H
O
3) 5-Methoxy-2-[[(methoxy-3,5-dimethylpyridin-2-yl)methyl]sulphonyl]-1 H-
benzimidazole ( Omeprazole Sulphone )
OCH3
CH3 CH3 OCH3
N
O
N CH2 S N
O H
By HPLC
Page No. 55
OMEPRAZOLE PELLETS
Apparatus
The liquid chromatograph equipped with variable wavelength detector and integrator.
Mobile Phase: Weigh about1.400 gms of Disodium hydrogen phosphate and dissolve in 1000 ml of HPLC
grade water and add 608 ml of Acetonitrile and adjust the pH to 7.2 with 1N ortho phosphoric acid.
Sample preparation: Weigh accurately about 0.01 gms of sample in a 10 ml volumetric flask dissolve and
dilute to volume with mobile phase.
BATCH NO : O/WS/01
Page No. 56
OMEPRAZOLE PELLETS
02. Assay : 99.91%
03. Identification by I.R. : To be concordant with the reference standard.
Storage conditions:
Omeprazole Working standard B.No. O/WS/01 is standardized with respect to USP Reference
standard Lot No. H1B211
Working Reference
Sl.No Test Specifications
Standard Result Standard Result
Assay by HPLC NLT 98.0% and NMT
01 (on dry basis) 99.91% 100.02% 102.0%
Sum of
02 Impurities 0.09% 0.02% NMT 1.0%
To be concordant with
03 I.R. Complies Complies the reference standard.
Remarks: The prepared working standard complies with respect to values obtained as per
Reference standard.
Page No. 57
OMEPRAZOLE PELLETS
BATCH NO : O/WS/01 MFG. DATE : JUNE, 2004
MFG. LICENCE NO : 22/RR/AP/99/B/R/C EXP DATE : MAY 2007
TEST PROTOCOL : USP
S.No Test Specifications Result
01 Description A white or almost white powder A White powder
02 Solubility Very slightly soluble in water, soluble in Alcohol, in Complies
Methanol and in Methelene Chloride, dissolves in
diluted solutions of Alkali Hydroxides
03 Identification
a) By TLC: The Rf value of principal spot of test should Complies
correspond to the Rf value of USP Omeprazole R.S.
b) By Infrared The IR spectrum concordant with the spectrum of Complies
Absorption Omeprazole CSR.
04 Completeness of Should meet the requirements, a solution in Complies
solution methelene chloride containing 20 mg per ml. being
used.
05 Color of Solution Determine the absorbance of the solution prepared for Complies
the Completeness of solution test at 440 nm, in 1-cm
cells, using methylene chloride as the blank. The
absorbance is not greater than 0.10.
06 Loss on drying at 600C NMT 0.5 % W/W 0.115%
for 4 hrs under vacuum
07 Residue on Ignition NMT 0.1 % W/W 0.052%
08 Heavy Metals NMT 0.002% Complies.
09 Organic volatile Should meet the requirements. Complies.
impurities
10 Chromatographic
Purity:
Method 1 (By TLC):
a) Individual impurity NMT 0.3% 0.05%
b) Sum of Impurities NMT 1.0% 0.20%
Method 2 (By HPLC):
a) Individual Impurity NMT 0.3% 0.04%
b) Sum of Impurities NMT 1.0% 0.09%
11 Assay by HPLC NLT 98.0% and NMT 102.0% 99.91%
(On dry Basis)
Remarks: The above product complies the USP Specifications with respect to the above tests.
Packaging and Storage: Preserve in tight containers and store in a cold place, protected from moisture.
Page No. 58
OMEPRAZOLE PELLETS
Packing and labeling material are stored in a separate place and packing materials
like polythene bags and Fiber/HDPE drums and labels are conveniently stored in locked
cabinets. Records are kept for packaging and labeling material and distribution for use.
POLYTHENE BAGS:
These bags are used for packing the finished product. Quality is suitable for food
grade and a certificate is obtained from the supplier for each consignment.
FIBER/ HDPEDRUMS:
Fiber Drums, HDPE Drums which are used for the packing the product, are of
standard quality with regard to weight, strength and durability . The following tests are
conducted before accepting consignment.
4.1 SPECIFICATIONS
Page No. 59
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Page No. 60
OMEPRAZOLE PELLETS
HDPE DRUMS
5. BATCH ANALYSIS
Page No. 61
OMEPRAZOLE PELLETS
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OMEPRAZOLE PELLETS
Page No. 63
OMEPRAZOLE PELLETS
BATCH NO : O/200405055 MFG. DATE : MAY, 2004
DATE OF ANALYSIS : MAY 2004 EXP. DATE : APRIL, 2007
S.No Test Specifications Result
6. STABILITY STUDIES
Conditions:
Page No. 64
OMEPRAZOLE PELLETS
Schedules : Sample tested are initial and at every month for 6 months.
Schedules : Sample tested are initial and at 3,6,9 and 12 months upto submission and continued
till completion as per schedule.
Number of batches :
Accelerated : First three commercial batches will be kept for stability studies. Whenever a change
implemented, one to three batches will be kept for stability depending on level of change.
Long term : First three commercial batches will be kept for stability studies.
Samples packing :
Testing Parameters:
01). Description
02). Identification
3) Related Impurities by HPLC
4) Assay
Page No. 65
OMEPRAZOLE PELLETS
TIME
TESTS
Initial
1Month 2Months 3Months 4 Months 5Months 6Months
A white or A white or A white or A white or A white or A white or A white or
almost almost almost almost almost almost almost
Description
white white white white white white white
powder powder powder powder powder powder powder
Identification
Complies Complies Complies Complies Complies Complies Complies
Related
Impurities by 0.11% 0.11% 0.11% 0.13% 0.13% 0.13% 0.14%
HPLC
Assay by
99.75% 99.74% 99.73% 99.72% 99.71% 99.67% 99.65%
HPLC
Date of
analysis 26.10.2002 26.11.2002 26.12.2002 26.01.2003 26.02.2003 26.03.2003 26.04.2003
Analysed on
25.10.2002 25.11.2002 25.12.2002 26.01.2003 26.02.2003 26.03.2003 26.04.2003
Page No. 66
OMEPRAZOLE PELLETS
Date of
analysis 26.11.2002 26.12.2002 26.01.2003 26.02.2003 26.03.2003 26.04.2003 26.05.2003
Analysed on
25.11.2002 25.12.2002 25.01.2003 25.02.2003 25.03.2003 25.04.2003 25.05.2003
Page No. 67
OMEPRAZOLE PELLETS
TESTS
Initial 1Month 2Months 3Months 4 Months 5Months 6Months
Related
Impurities by 0.07% 0.09% 0.09% 0.09% 0.11% 0.12% 0.13%
HPLC
Assay by
99.81% 99.79% 99.78% 99.76% 99.76% 99.75% 99.73%
HPLC
Date of
analysis 26.12.2002 26.01.2003 26.02.2003 26.03.2003 26.04.2003 26.05.2003 26.06.2003
Analysed on
25.12.2002 25.01.2003 25.02.2003 25.03.2003 25.04.2003 25.05.2003 25.06.2003
Page No. 68
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Initial
3Months 6Months 9 Months 12 Months 15Months 18 Months
Description A white or A white or A white or A white or A white or A white or A white or
almost almost almost almost almost almost almost
white white white white white white white
powder powder powder powder powder powder powder
Identification Complies Complies Complies Complies
Complies Complies Complies
Related
Impurities by 0.11% 0.12% 0.13% 0.13% 0.15% 0.15% 0.16%
HPLC
Assay by
99.75% 99.71% 99.70% 99.66% 99.65% 99.59% 99.51%
HPLC
Date of
analysis 26.10.2002 26.01.2003 26.04.2003 26.07.2003 26.10.2003 26.01.2004 26.04.2004
Page No. 69
OMEPRAZOLE PELLETS
Related
Impurities by 0.14% 0.15% 0.15% 0.16% 0.18% 0.18% 0.19%
HPLC
Assay by
99.72% 99.71% 99.69% 99.65% 99.64% 99.63% 99.62%
HPLC
Date of
analysis 24.11.2002 24.02.2003 24.05.2003 24.08.2003 24.11.2003 24.02.2004 24.05.2004
Page No. 70
OMEPRAZOLE PELLETS
Related
Impurities by 0.07% 0.07% 0.09% 0.11% 0.13% 0.14% 0.14%
HPLC
Assay by
99.81% 99.80% 99.78% 99.77% 99.65% 99.64% 99.62%
HPLC
Date of
analysis 26.12.2002 26.03.2003 26.06.2003 26.09.2003 26.12.2003 26.03.2004 26.06.2004
Conclusion: Based on above study and observation the product is stable under specified conditions of
storage. There is no significant change in accelerated studies.
Page No. 71
OMEPRAZOLE PELLETS
Name of the Material/Code: OMEPRAZOLE POWDER Category : Finished Product
Address: Flat No. 302,Bhanu Enclave, Sunder Nagar, Erragadda, Hyderabad-500 038, INDIA.
Phone: +91-40-23700421/23813969/23812317. Fax: +91-40-23705088.
Web: www.metroapi.com E-mail: api@metroapi.com.
WARNING STATEMENT:
WARNING : NOT FOR DIRECT HUMAN CONSUMPTION. AVOID INGESTION, INHALATION & SKIN CONTACT.
FOR PROCESSING USE ONLY.
SECTION 1 – IDENTITY
SYNONYMS : ---------
Formula : C17H19N3O3S
SECTION 2 - HAZARDOUS INGREDIENTS
PRINCIPAL HAZARDOUS COMPONENTS ( S ) / [ CHEMICAL & COMMON NAME ( S ) ]
NAME PERCENTS THRESHOLD LIMIT
VALUE ( LIMITS )
(RS)-5-Methoxy-2-[[(4-methoxy-3,5 PURE MATERIAL NOT ESTABLISHED
-dimethylpyridine-2-yl)methyl]
Sulphinyl]-1H-benzimidazole
Page No. 72
OMEPRAZOLE PELLETS
Name of the Material/Code: OMEPRAZOLE POWDER Category : Finished Product
SECTION 3 – PHYSICAL AND CHEMICAL CHARACTERISTICS
(Fire & Explosion Data )
BOILING : N /A
SPECIAL FIRE FIGHTING PROCEDURE : AS with all fires, evacuate personnel to safe area. Fire fighter
should use self-contained breathing equipment and
protective clothing.
UNUSUAL FIRE AND EXPLOSION : This material is assumed to be combustible. As with all dry
HAZARDOUS powders it is advisable to ground mechanical equipment in
contact with dry material to dissipate the potent build up of
static electricity. When heated to decomposition, material
emits toxic fumes. Emits toxic fumes under the conditions.
Page No. 73
OMEPRAZOLE PELLETS
Name of the Material/Code: OMEPRAZOLE POWDER Category : Finished Product
Page No. 74
OMEPRAZOLE PELLETS
Name of the Material/Code: OMEPRAZOLE POWDER Category : Finished Product
EMERGENCY AND FIRST AID PROCEDURE : Remove from exposure. Remove contaminated clothing.
Person developing serious hypersensitivity reactions must
receive immediate medical attention. Upon eye or skin
contact, flush affected area with copious quantities of
water. Obtain medical attention.
Page No. 75
OMEPRAZOLE PELLETS
Name of the Material/Code: OMEPRAZOLE POWDER Category : Finished Product
PRECAUTIONS TO BE TAKEN IN HANDLING : Store in tight container as defined in the United States
AND STORAGE Pharmacopoeia. This material should be handled and
stored per label and other instructions to ensure product
integrity.
OTHER PRECAUTIONS : Avoid contact with eyes, skin or clothing. Avoid breathing
dust or mist. Use with adequate dust control. Wash
thoroughly after handling. Wear fresh clothing daily. Wash
contaminated clothing before reuse. Do not permit eating,
drinking or smoking near material.
STEPS TO BE TAKEN IN CASE MATERIAL IS : Wear approved respiratory and chemically compatible
SPILLED OR RELEASED gloves. Vacuum or sweep of spillage in appropriate
container for waste disposal. Wash contaminated clothing
before reuse. Ventilate area and wash spill site.
WASTE DISPOSAL METHODS : Dispose of waste in accordance with all applicable laws.
8. VENDORS LIST
The company is procuring rawmaterials from approved vendors.
Page No. 76
OMEPRAZOLE PELLETS
02 Methanol 1. Aerochem, Hyderabad.
2. Jay Ambe Enterprises, Hyderabad
3. Best chem, Hyderabad
4. Jay Enterprises, Mumbai
5. Vijayasri chem Agencies, Hyderabad
6. Omega Enterprises, Mumbai
7. Fine chem, Hyderabad
03 Caustic Soda flakes 1. Rasayan Marketing, Hyderabad
2. Laxmi Nursing Chemicals, Hyderabad
3. The Andhra Sugars Ltd. Hyderabad
4. Parichem Pharma, Hyderabad
5. Srivasta Enterprises, Hyderabad
04 Dimethyl Sulphate 1. Industrial solvents, Hyderabad.
2. Herms chemicals company (p) Ltd.
05 Chloroform 1. Swastik Chemicals, Hyderabad
2. Jay Ambe Enterprises, Hyderabad
3. Sayar Chemicals, Hyderabad
4. S.N.Sales, Hyderabad
06 Toluene 1. Swastik Chemicals, Hyderabad
2. Sandeep Enterprises, Hyderabad
3. Vardhman Chemical Industries,
Hyderabad
4. Unichem Corporation, Hyderabad.
07 Ammonium per sulphate 1. Gujarat persalts private limited. Gujarat
08 Activated carbon 1. Swastik Chemicals, Hyderabad
09 Thionyl chloride 1. Parichem Pharma, Hyderabad
2. Sarthank Enterprises, Hyderabad
10 2-Mercapto 5-methoxy benzimidazole 1. Everest organics Ltd., Hyderabad
2. Sharon Bio medicine, Mumbai
3. Nirayu Ltd., Baroda
11 Ethyl acetate 1. Vardhman chemical industries,
Hyderabad
2. Sandeep Enterprises, Hyderabad
3. Sri Vasavi chemicals corporation, Hyd.
12 Hydrose 1. Srivasta Enterprises, Hyderabad
2. Sandeep Enterprises, Hyderabad.
13 EDTA 1. Sandeep Enterprises, Hyderabad
2. Classic chemicals, Hyderabad.
3. Piyush chemicals, Hyderabad.
14 Triethyl amine 1. Balaji Amines Ltd., Hyderabad
2. Parichem Pharma, Hyderabad.
15 Ammonium molybdate 1. Yogi dye Chemicals, Mumbai
2. Rajesh Enterprises, Mumbai
16 Acetone 1. Vardhaman Chemical Industries,
Hyderabad
2. Unichem Corporation, Hyderabad
3. Swastik Chemicals, Hyderabad
17 Iso propyl alcohol 1. Navodaya Chemicals, Hyderabad
2. Jay Ambe Enterprises, Hyderabad
3. Ponpure Chem (P) Ltd. Hyderabad
4. Swastik Chemicals, Hyderabad.
18 Methylene chloride 1. Swastik Chemicals, Hyderabad
Page No. 77
OMEPRAZOLE PELLETS
2. Jay Enterprises, Mumbai
3. Vardhman chemical Industries,
Hyderabad
4. APL chemi labs, Hyderabad
5. Aerochem, Hyderabad.
Page No. 78