FIELD OF THE INVENTION
The present invention relates to an improved process for the preparation of Form-A of sodium salt of 5-methoxy-2-[ [ ( 4-methoxy-3,5-dimethyl-2-pyridinyl )methyl] sulfmyl]-lH-benzimidazole, known under the generic name Omeprazole sodium salt. Omeprazole sodium can be depicted as Formula- (1).

Omeprazole and its salts are useful for inhibiting gastric acid secretion as well as for
providing gastrointestinal cytoprotective effects in mammals and man.
BACK GROUND OF THE INVENTION
European Patent EPS 129 disclosed the Omeprazole and its pharmaceutical acceptable salts.
The specific alkaline salt of Omeprazole, such as sodium salt, is disclosed in EP 124 495. The
Omeprazole sodium salt produced according to examples 1 and 2 of EP 124 495 is a mixture
of crystal forms and amorphous material.
WO 99/00380 disclosed various forms of Omeprazole sodium and those are designated as
Form-A, Form-B and Form-X. These forms differ from each other in respect of physical
properties, stability, spectral data and methods of preparation. Form-X of Omeprazole sodium

is a physically unstable and mixture of crystal forms and amorphous material. Form-B is a
physically stable crystalline hydrate form.
WO 99/00380 disclosed a process for the synthesis of Form-A of Omeprazole sodium, which
comprises the steps of treating Omeprazole with an aqueous base Na+ B-, where in Na
denotes sodium and B denotes hydroxide or alkoxide, Ion exchangers, resins which releases
Sodium Cation, at room temperatiu"e in an isopropanal solution, optionally containing water,
precipitation of Omeprazole Form-A at 50°C with methanol, seeding of Reaction mass with
Omeprazole sodium methanol wet, isolation of product at -8°C to -9oC and finally drying of
the product in a rotary dryer at 35mbar with a jacket temp of 65°C, and 39-87 mbar with a
jacket temperature of 50°C for 3 days, overall yield is 74.6%.
The resulting Omeprazole sodium Form-A, which is prepared according Example: 3 in
WO99/00380 is a hydrate with one to two water molecules, of which one water molecule is
strongly bound in the crystal structure, while the other water molecule is easily removed by
drying. The resulting dried substance containing one strongly bound water molecule is very
hygroscopic and absorbs water rapidly under normal conditions.
It is also stated that Omeprazole sodium Form-A produced according example: 3 in WO
99/00380 is thermodynamically unstable, under certain strong conditions completely or partly
converted into another form. Other drawbacks of this process are, time consuming process,
poor solubility and transmittance.
There is a constant need to prepare pharmaceutically stable crystalline forms of the active
substance Omeprazole sodium and an improved process for the preparation of the same, in an
industrially simple and readily feasible way with high yield and proportions of residual

solvents and impurities, i.e. the preparation of related substances and degradation products is
low and minimal.
Hence, the objective of the present invention is to provide an improved process for the
preparation of stable Form-A of Omeprazole sodium of Formula-(l).
SUMMARY OF THE INVENTION:
The present invention is directed to an improved process for the preparation of stable Form-A
of Omeprazole sodium of Formula-(l), which eliminates the drawbacks of previously known
processes.
The process for the preparation of Form-A of Omeprazole sodium of the present invention,
comprises of dissolution of Omeprazole in Aqueous base , Na"^ B" where in Na denotes
sodium and B denotes hydroxide or alkoxide, ion exchangers, resins which releases Sodium
Cation, at Room temperature in an appropiate solvent consisting of C3-C7 branched or
chained hydrocarbons, C2-C7 chained or baranched ethers, cyclic ethers, lower fatty acid
esters, aliphatic ketones, halogenated hydrocorbon solvents or nitrile solvents with optionally
containing water, followed by neutralisation of resultant solution by an appropriate anti
solvent in which product is poorly soluble.
It is also observed that Form-A of Omeprazole obtained by above process is stable with
relatively high yields, good purity and improved properties i.e. Solubility and trasmittency.
The process is commercially viable and well suitable for industrial scale up.
BRIEF DESCRIPTION OF THE ACCOMPANYING DRAWING:
Fig. 1 is a diagram showing the results of X-ray diffraction of the present invention.
Fig. 2 is a diagram showing the results of IR spectrum of the present invention.

DETAILED DESCRIPTION OF THE INVENTION
The objective of the present invention is to provide novel and improved process for the preparation of crystaUine Form-A of Omeprazole Sodium of Formula-(l), which is simple, commercially viable and well suitable for industrial process.
The crystalline nature of Form-A of Omeprazole sodium of present invention is characterized by its X-ray diffractogram, Differential Scanning Colorimetry thermogram and IR spectrum. The X-ray diffraction pattem of Form-A of Omeprazole sodium was measured on a Bruker Axe, DS Advance Powder X-ray Diffractometer with Cu K alpha-1 Radiation source. The 2-theta values and their intensity percentages of relevant peaks in X-ray powder diffraction pattem of crystalline Form-A of Omeprazole sodium are shown in the Table-1. Table-1.


The crystalline nature of Form-A of Omeprazole sodium was characterized by its X-ray
powder diffractogram and the relevant diffractogram is substantially as depicted in Figure (1).
The moisture content of the Form-A of Omeprazole sodium was characterized by its thermo
gravimetric analysis at a temperature range of 0-250^C and by KF method. The thermo
gravimetric analysis results have shown that moisture content of the Form-A of Omeprazole
of present invention as 4.7%, which shows the hydrated nature of compound.
The present invention further provides the Infrared data for Form-a of Omeprazole sodium,
which was measured by KBr-transmission method with identified significant peaks around
3439 and 2950 cm ■The present invention provides the IR spectrum of crystalline Form-A of Omeprazole sodium
as depicted in Figure (2).

Another embodiment of the present invention is to provide the process for the preparation of Form-A of Omeprazole sodium, which comprises.
i) dissolution of Omeprazole in an aqueous base, Na^B" where in Na denotes
sodium and B denotes hydroxide or alkoxide, Ion exchangers, resins which releases sodium cation, at room temperature, in an appropiate solvent consisting of C3-C7 branched or chained hydrocarbons, C2-C7 chained or branched ethers, cyclic ethers, lower fatty acid esters, aliphatic ketone solvents, halogenated hydrocorbon solvents or nitrile solvents with optionally containing water;
ii) neutralising the reacation mixture of step(i) using an appropriate anti solvent in which product is poorly soluble form the same group of solvents as mentioned in step (i).
iii) gently stirring the reaction mixture of step (ii) for 0-24 hrs at room temperature.
iv) cooling the reaction mixture of step (iii) till the solid mass crysatUizes.
v) filtering the isolated solid of step (iv) by conventional techniques,
accompanied by washing with a solvent as mentioned in step (i).
vi) drying the isolated compound of step(v) at 30-70 ^ C preferably at a temperature of 50-60 ^ C to afford Form-A of Omeprazole sodium.
It is note worthy to mention that the starting material of the above process,
Omeprazole can be prepared as per procedures known in prior art.

Thus, the present invention is directed to an improved process for the preparation of Form-A
of Omeprazole sodium, which is non-hydroscopic, with permissible residual solvent limits,
which renders it well suited for pharmaceutical formulations.
Form-A of Omeprazole, obtained by the above process is confirmed as thermodynamically
more stable than any other prior art processes.
The present invention is described in detail with examples given below that are provided by
the way of illustration only and therefore should not be construed to the limit scope of
invention.
Preparation of Form-A of Omeprazole sodium:
EXAMPLE-1:
Omeprazole (100 grams) was added to the mixture of Tetrahydrofuran (400ml), sodium hydroxide (11.6gms) and water (22 ml) and stirred for one hour at room temperature. The resultant reaction mixture was filtered through hyflow bed and then bed was washed with tetrahydrofuron (25 ml). Thus obtained clear filtrate was added to ethylacetate (1.0 lit) at room temperature and the reaction mixture temperature was increased to 30 ° C accompanied by gentle stirring for 2 hours to crystallize the solid mass. The solid mass was filtered under reduced pressure , washed with ethylacetate (50 ml) and dried at the temperature of 50-70*^C to afford the crystalline polymorph Form-A of Omeprazole sodium. (Weight: 108.8 grams, 97.3. %; M.C. by KF is 4.66 %; Purity: 99.95%). EXAMPLE - 2:
Omeprazole (50 grams) was added to the mixture of acetonitrile (200 ml), sodium hydroxide (5.8gms) and water (11.0 ml) and stirred for 40 minutes at a temperature of 20-25° C.

acetonitrile (500 ml) was added to the reaction mixture at room temperature and agitated for
1-1.5 hours. The resultant reaction mixture was filtered under reduced pressure and washed
with acetonitrile (100.0 ml) dried at the temperature of 50-70°C to afford the crystalline
polymorph Form-A of Omeprazole sodium.
(Weight: 53.90 grams, 96.35%; M.C. by KF is 6.2%; 99.88%).
EXAMPLE-3:
Omeprazole (25 grams) was added to the mixture of dichloromethane (100 ml), sodium
hydroxide (3.2 grams) and water (5.0 ml) and stirred for 40 minutes at 30 ° C temperature.
methyl isobutyl ketone(200 ml + 100 ml) was added to the reaction mixture and stirred for 2.5
hours at 30° C. The resultant reaction mixture was filtered and washed with methyl isobutyl
ketone (50 ml) and dried at the temperature of 50-70^C to afford the crystalline polymorph
Form-A of Omeprazole sodium.
(Weight: 26.8 grams, 95.88; M.C. by KF is 4.7%; Purity: 99.887%)
EXAMPLE-4:
Omeprazole (100 grams) was added to the mixture of acetone (100 ml), sodium hydroxide
(12.8 grams) and water (20.0 ml) and stirred for 50 minutes at 30 ° C temperature.
The resultant reaction mixture was filtered through hyflow bed and then bed was washed with
acetone (25 ml). Thus obtained clear filtrate was added to tertiary butyl acetate (800.0 lit) at
room temperature and the reaction mixture temperature was increased to 30 ° C accompanied
by gentle stirring for 2 hours to crystallize the solid mass. The solid mass was filtered under
reduced pressure and dried under reduced pressure to afford Form-A of Omeprazole sodium.
Further Form-A of Omeprazole was dried at a temperature of 50-70° C.
(Weight: 105.0 grams, 93.85%; Purity: 99.88%)

DETAILED DESCRIPTION OF THE ACCOMPANYING DRAWING
Fig. 1 is a diagram showing the results of X-ray diffraction of the novel process.
Vertical axis: Intensity (CPS); Horizontal axis: 2 Theta (degrees) values.
The significant 29 values (degrees) obtained are 5.64,11.97,12.19, 12.86, 13.63, 16.47, 16.95,
18.83, 20.09, 21.21, 22.52, 23.15, 23.68, 24.56, 25.10, 25.4, 25.96, 28.48, 30.55, 31.49, 34.36,
35.33 and 36.98 degrees.
Fig. 2 is a diagram showing the results of IR spectrum of the Novel process, with identified
significant peaks at about 3439 and 2950 cm-1
Vertical axis: Wave length (in Cm-1); Horizontal axis: Transmission (in %).
We claim:
1. An improved process for the preparation of crystalline Form-A of the sodium sah of 5-methoxy-2-[ [ (4-methoxy-3,5-dimethyl-2-pyridinyl )methyl] sulfinyl] -IH-benzimidazole (Omeprazole sodium), which comprises;
i) dissolution of Omeprazole in an aqueous base, Na^B' where in Na denotes
sodium and B denotes hydroxide or alkoxide. Ion exchangers, resins which releases sodium cation, at room temperature, in an appropiate solvent consisting of C3-C7 branched or chained hydrocarbons, C2-C7 chained or branched ethers, cyclic ethers, lower fatty acid esters, aliphatic ketone solvents, halogenated hydrocorbon solvents or nitrile solvents with optionally containing water;

ii) neutralising the reacation mixture of step(i) using an appropriate anti solvent in
which product is poorly soluble form the same group of solvents as mentioned
in step (i). iii) gently stirring the reaction mixture of step (ii) for 0-24 hrs at room
temperature,
iv) cooling the reaction mixture of step (iii) till the solid mass crysatUizes.
v) filtering the isolated solid of step (iv) by conventional techniques,
accompanied by washing with a solvent as mentioned in step (i). vi) drying the isolated compound of step(v) at 30-70 o C preferably at a
temperature of 50-60 ° C to afford Form-A of Omeprazole sodium.
2. A process according to claim 1 of step (i) where in preferable solvents are
tetrahydrofuran, acetonitrile, ethyl acetate, acetone or dichloromethane.
3. A process according to claim 1 of step (i) where in preferable anti solvents are
ethyl acetate, acetonitrile, methyl isobutyl ketone or tertiary butyl acetate.
4 The process for the preparation of crystalline Form- A of Omeprazole sodium is substantially as here in described and exemplified.