Title of Invention	PROCESS FOR THE PREPARATION OF HIGHLY PURE RABEPRAZOLE SODIUM
Abstract	This invention relates to an improved process for the preparation of highly pure Rabeprazole sodium, (±)-sodium-2-[[[4-(3-methoxypropoxy)-3-methy]-2-pyridiny)]methy!]sulfinyl]-!H-benzimidazole by using lyophilization.

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FIELD OF THE INVENTION The present invention relates to a process for the preparation of highly pure Rabeprazole sodium using lyophilization. BACKGROUND OF THE INVENTION There are a large number of patents and patent applications disclosing differently substituted 2-(2-pyridinyimethylsulphinyl)-lH-ben2imidazoles. This class of compounds is inhibitors of gastric acid secretion and hence is useful as anti-ulcer agents. Several methods are already known to prepare the same. US Patent 5,045,552 as well as WO 01/04109 have disclosed the preparation of Rabeprazole sodium by known traditional procedures, such as dissolution of ttie product in a mixture of stoichiometric quantity of aqueous sodium hydroxide and ethanol, evaporation of the solvent to remove water as an azeotropic mixture, drying the residue at low pressure and then crystallization of the residue with scantly polar solvent such as diethyl ether, /ert-butyl methyl ether etc. This procedure of preparing sodium salt has numerous disadvantages such as large volume of solvents is required to azeotropically remove water and to crystallize out the product, which are difficult to recycle or dispose of in an environmentally acceptable manner. A further disadvantage of this process is the presence of higher residual solvent content in the product resulting in lower potency. This method is not suitable for industrial scale preparation of Rabeprazole sodium. OBJECTS OF THE INVENTION It is therefore an object of this invention to propose an improved method for the preparation of Rabeprazole sodium without the use of organic solvents. It is another object of present invention to avoid the evaporation of azeotropic mixture disclosed in the prior art. It is a further object of the present invention to prepare highly pure Rabeprazole sodium in dry form, in quantitative yield and having higher potency. We have studied the drawbacks of the prior art and the use of organic solvents complicates the preparation of Rabeprazole sodium and makes it commercially non-viable. After considerable studies, we have now unexpectedly discovered that the title compound can be easily prepared by using only an aqueous solution. SUMMARY OF THE INVENTION equivalent of sodium hydroxide. The quantity of water is in the range of 3 to 7 pans by volume and preferably it is 5 parts by volume. The desired Rabeprazole sodium is obtained directly by lyophilizing the solution. Lyophilization is all together a different technique of removing a solvent from the solution. Lyophilization is defined as a stabilizing process in which the substance is first frozen and then quantity of the solvent is reduced first by sublimation (Primary drying) and then by desorption (Secondary drying) to values that will no longer support biological growth or chemical reaction. The key term being that lyophilization is a stabilizing process. It fijrther enhances the stability of the product and improves appearance, uniformity and imparts low moisture content to the product (Ref: Lyophilization - Introduction and Basic principles by Thomas A Jennings). Major advantages realized in the instant invention as compared to prior art are increased product purity and absence of residual solvent impurity. No solvent is required to isolate the product and hence no mother liquor is obtained which is difficult to regenerate. The solvent employed is only water, thus offering great ecological advantage. Apart from all these, quantitative yield of Rabeprazole sodium is obtained. We now describe the invention with reference to the following Example: Example PREPARATION OF RABEPRAZOLE SODIUM Sodium hydroxide (5.62 g) was dissolved in DM water (200 ml) and cooled to 4-5'C. Rabeprazole (50 g) was added and mixture stirred to obtain a clear solution. The solution was treated with 2 g of carbon DC-enoanticromos for 30 min at S-IO^C. Carbon was removed by fiUration and residue washed with DM water (2x25 ml). The contents were lyophilized using standard method. Rabeprazole sodium was obtained as a white powder. Yield: 52 g (97%) of theory). Assay: 99.5%i. No residual solvent was detected in the product byGC. WE CLAIM: 1. A process for the preparation of (±)-sodium-2-[[[4-(3-methoxypropoxy)-3-methyl-2- pyridinyl]methyl]sulfinyl]-lH-benzimidazole {Rabeprazole sodium) of Formula 1, subjecting the above solution to lyophilization and isolate highly pure Rabeprazole sodium of Formula I. 2. The process according to claim 1 wherein exactly one mole equivalent of sodium hydroxide as to Rabeprazole of Formula U is used. 3. The process according to claim 1, wherein the quantity of water used is 3 to 7 parts by volume and preferably 5 parts by volume of Rabeprazole of Formula 11. 4. A process for the preparation of Rabeprazole sodium of Formula I as herein described.

Documents:

0419-mas-2002 abstract-duplicate.pdf

0419-mas-2002 abstract.pdf

0419-mas-2002 claims-duplicate.pdf

0419-mas-2002 claims.pdf

0419-mas-2002 correspondence-others.pdf

0419-mas-2002 correspondence-po.pdf

0419-mas-2002 description (complete)-duplicate.pdf

0419-mas-2002 description (complete).pdf

0419-mas-2002 form-1.pdf

0419-mas-2002 form-19.pdf

0419-mas-2002 form-3.pdf