This application claims priority to Indian patent application numbered, 3289/CHE/2011 filed on Sep 23, 2011 the contents of which are incorporated by reference in their entirety.

FIELD OF THE INVENTION:

The present invention provides a process for the preparation of esomeprazole magnesium containing R-isomer in the range of 0.1 to 0.5% by weight. The present invention further relates to a pharmaceutical composition comprising esomeprazole magnesium containing R-isomer in the range of 0.1 to 0.5% by weight.

BACKGROUND OF THE INVENTION:

Several substituted 2-(2-pyridylmethyl) sulphinyl-1H-benzimidazoles derivatives such as omeprazole, lansoprazole, pantoprazole, rabeprazole and ilaprazole are well-known proton pump inhibitors. The asymmetrically substituted sulfur atom of the sulfinyl is chiral in nature. This type of chiral sulfoxides has been discussed in the scientific literature in the late seventies and there is no literature evidence for efficient asymmetric synthesis for the single enantiomer thereof.

The single enantiomers of pharmacologically active compounds have met an increased interest in recent years because of improved pharmacokinetic and biological properties. Therefore, there is a demand for an enantioselective process that can be used in large scale manufacture of the single enantiomers of pharmacologically active compounds, such as for instance optically pure, substituted 2-(2-pyridinylmethylsulphinyl)-1 H-benzimidazoles.

(S)-5-Methoxy-2[[(4-methoxy-3,5-dimethyl-2-pyridinyl)-methyl]sulfinyl]-1H-benzimidazole (Esomeprazole ) represented by Formula -I,

US5948789 discloses a process for the enantioselective synthesis of esomeprazole by asymmetric oxidation of pro-chiral sulphide . In this patent the oxidation is carried out in an organic solvent with an oxidizing agent in the presence of a chiral titanium complex, optionally in the presence of a base, wherein the titanium complex has been generated in situ and it afforded either as a single enantiomer or enantiomerically enriched with S-isomer of omeprazole.

US6875872 describes magnesium salt of the (-) enantiomer of 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1 H-benzimidazole (esomeprazole magnesium) with an optical purity greater than about 94.0% enantiomeric excess. The '872 patent discloses the preparation of esomeprazole magnesium containing high optical purity from a non-aqueous medium by reaction of a crude esomeprazole with a methanolic magnesium methoxide, followed by separation of the inorganic by-products and crystallization of the resultant esomeprazole magnesium from a mixture of methanol and acetone.

US20110207779 discloses a process for the preparation of esomeprazole magnesium dihydrate containing R-isomer in the range of about 0.1% to 1% by weight. The process comprising, providing a solution of esomeprazole magnesium in an organic solvent, adding omeprazole magnesium and isolating a esomeprazole magnesium containing R-isomer in the range of about 0.1% to 1% by weight.

According to the above process, the organic solvent leads to formation of volatile organic impurities, since it is a final step of the product.

Thus, the present invention is provides a process for the preparation of esomeprazole magnesium containing R-isomer in the range of 0.1 to 0.5% by weight, in which the R-isomer content is specified in intermediate stage itself.

SUMMARY OF THE INVENTION:

The main aspect of the present invention is to provide a process for the preparation of esomeprazole magnesium containing R-isomer in the range of 0.1 to 0.5% by weight comprising the steps of:

a) providing a solution of esomeprazole or a salt in a solvent,

b) adding a solution of omeprazole or a salt,

c) reacting with magnesium source, and

d) isolating esomeprazole magnesium containing R-isomer in the range of 0.1 to 0.5% by weight.

Another aspect of the present invention is to provide a pharmaceutical composition of esomeprazole magnesium containing R-isomer in the range of 0.1 to 0.5% by weight.

DETAILED DESCRIPTION OF THE INVENTION:

The present invention provides a process for the preparation of esomeprazole magnesium containing R-isomer in the range of 0.1 to 0.5% by weight. The present invention further relates to a pharmaceutical composition of esomeprazole magnesium containing R-isomer in the range of 0.1 to 0.5% by weight.

The main embodiment of the present invention is to provide a process for the preparation of esomeprazole magnesium containing R-isomer in the range of 0.1 to 0.5% by weight comprising the steps of:

a) providing a solution of esomeprazole or a salt in a solvent,

b) adding a solution of omeprazole or a salt,

c) reacting with magnesium source, and

d) isolating esomeprazole magnesium containing R-isomer in the range of 0.1 to 0.5% by weight.

According to the present invention, esomeprazole or a salt is dissolved in a solvent and a solution of omeprazole or a salt is added at 20-35°C, followed by reacting with magnesium source at 5-15°C to isolate esomeprazole magnesium.

The solvent used for dissolution of esomeprazole salt is selected from water, methanol, ethanol or mixture thereof.

The omeprazole salt is selected from omeprazole sodium or omeprazole potassium. The solvent used for the dissolution of omeprazole or a salt is selected from water, methanol, ethanol or mixture thereof.

The magnesium source is selected from magnesium sulphate, magnesium chloride or magnesium acetate,

Another embodiment of the present invention is to provide a pharmaceutical composition of esomeprazole magnesium containing R-isomer in the range of 0.1 to 0.5% by weight.

The following non-limiting examples illustrate specific embodiments of the present invention. They should not construe it as limiting the scope of present invention in any way.

EXAMPLE:

Preparation of esomeprazole magnesium contains R-isomer in the range of 0.1 to 0.5% by weight.

Omeprazole (0.22 g) was dissolved in a solution of sodium hydroxide (0.292 g in 4.4 ml) under stirring and kept a side. In another container, esomeprazole sodium (100 g) was dissolved in demineralized water (1000 mL) and above prepared omeprazole sodium solution was added under stirring. The resultant solution was filter through the hyflo bed and washed the bed with water (200 mL). The filtrate was added to the pre-cooled solution of magnesium chloride hexahydrate (33 g was dissolved in demineralized water (1000 mL)) at 5-15°C and maintained the stirring for 30-45 min. The precipitated solid was filtered and washed with chilled water. The obtained product was dried to get amorphous esomeprazole magnesium.

WE CLAIM:

1. A process for the preparation of esomeprazole magnesium containing R-isomer in the range of 0.1 to 0.5% by weight comprising the steps of:

a) providing a solution of esomeprazole or a salt in a solvent,

b) adding a solution of omeprazole or a salt,

c) reacting with magnesium source, and

d) isolating esomeprazole magnesium containing R-isomer in the range of 0.1 to 0.5% by weight.

2. The process according to claim 1, wherein the solvent used in step a) is selected from water, methanol, ethanol or mixture thereof.

3. The process according to claim 1, wherein the omeprazole or its salt is dissolved in a solvent selected from water, methanol, ethanol or mixture thereof,

4. The process according to claim 1, wherein the omeprazole salt is selected form omeprazole sodium or omeprazole potassium.

5. The process according to claim 1, wherein the magnesium source is selected from magnesium sulphate, magnesium chloride or magnesium acetate.

6. The process according to claim 1, wherein the isolated esomeprazole magnesium is either in crystalline form or in amorphous form.

7. The process according to claim 1, wherein the isolated crystalline esomeprazole magnesium is in hydrate form.

8. The process according to claim 1, wherein the isolated esomeprazole magnesium having water content in the range of 7.0-10.0 % wt/wt.