Salts of sitagliptin, process from the preparation and pharmaceutical composition therefore
View Patent ↗The present invention relates to pharmaceutically acceptable acid addition salts of sitagliptin, in particular anti-oxidant acid addition salts of sitagliptin and a process for its preparation. The present invention also provides a pharmaceutical composition using the pharmaceutically acceptable acid addition salts of sitagliptin.
1. A process for preparing an anti-oxidant acid salt of sitagliptin, or its solvates or hydrates thereof,
wherein the anti-oxidant acid is selected from the group consisting of caffeic acid, ferulic acid, and p-coumaric acid, and
wherein
the caffeic acid salt of sitagliptin is characterized by a X-ray diffraction (XRD) pattern in accordance with FIG. 1 , FIG. 2 , FIG. 3 , FIG. 4 , FIG. 5 , FIG. 6 , or FIG. 7 ,
the ferulic acid salt of sitagliptin is characterized by a XRD pattern in accordance with FIG. 8 , FIG. 9 , FIG. 10 , FIG. 11 , FIG. 12 , or FIG. 13 , and
the coumaric acid salt of sitagliptin is characterized by a XRD pattern in accordance with FIG. 14 , FIG. 15 , FIG. 16 , FIG. 17 , FIG. 18 , FIG. 19 , or FIG. 20 ,
comprising the steps of:
a) providing a mixture comprising sitagliptin and the anti-oxidant acid; and
b) isolating the anti-oxidant acid salt of sitagliptin.
2. The process of claim 1 , wherein step a comprises:
1) dissolving any form of sitagliptin in a solvent at a temperature to form a solution, and
2) adding the anti-oxidant acid to the solution.
3. The process of claim 2 , wherein the solvent is selected from the group consisting of water, lower alcohols, ketones, esters, ethers, C 5-7 hydrocarbons, nitriles, halogenated hydrocarbons, and mixtures thereof.
4. The process of claim 2 , wherein the solvent is selected from the group consisting of methanol, ethanol, isopropanol, acetone, ethyl acetate, tetrahydrofuran (THF), isopropyl ether (IPE), acetonitrile, and mixtures thereof.
5. The process of claim 2 , wherein the temperature is about 30° C. to reflux temperature.
6. The process of claim 1 , wherein step b is carried out by filtration.
7. The process of claim 2 , further comprising the step of cooling the solution to precipitation or concentrating the solution.
8. The process of claim 3 , wherein the C 5-7 hydrocarbons are linear, branched, or cyclic.
9. The process of claim 3 , wherein the C 5-7 hydrocarbons are saturated or unsaturated.