Pharmaceutical compositions of sitagliptin

Abstract

The present invention relates to stable oral pharmaceutical compositions of sitagliptin base and processes for the preparation thereof.

1 . A stable pharmaceutical composition comprising sitagliptin and at least one beneficial agent, wherein the composition is a bioequivalent composition to Januvia® and shows similar rate and extent of absorption to those of Januvia®, the currently marketed product of sitagliptin phosphate monohydrate in USA. 
     
     
         2 . The stable pharmaceutical composition according to  claim 1 , wherein the sitagliptin is in an amorphous form. 
     
     
         3 . The stable pharmaceutical composition according to  claim 1 , wherein the sitagliptin is in a crystalline form. 
     
     
         4 . The stable pharmaceutical composition according to  claim 1 , wherein the beneficial agent comprises a complexing agent, a pH modifying agent, a solubilizing compound, a stabilizing compound, a permeability enhancing compound, or a combination thereof. 
     
     
         5 . The stable pharmaceutical composition according to  claim 1 , wherein the beneficial agent is L-cysteine hydrochloride. 
     
     
         6 . The stable pharmaceutical composition according to  claim 1 , wherein the beneficial agent is alginic acid. 
     
     
         7 . The stable pharmaceutical composition according to  claim 1 , wherein the sitagliptin is in a micronized form. 
     
     
         8 . The stable pharmaceutical composition according to  claim 7 , wherein the sitagliptin has an average particle size diameter below 25 microns. 
     
     
         9 . The stable pharmaceutical composition according to  claim 1 , wherein the composition further comprises one or more pharmaceutically acceptable excipients comprising diluents, binders, disintegrants, glidants, lubricants, sweeteners/taste masking agents, compression aids, colorants, flavors and the combinations thereof. 
     
     
         10 . The stable pharmaceutical composition according to  claim 1 , wherein the composition is in the form of a solid dispersion. 
     
     
         11 . The stable pharmaceutical composition according to  claim 1 , wherein said composition retains at least about 90% of the potency of sitagliptin in the pharmaceutical composition after storing the composition at 40° C. and 75% relative humidity for at least three months. 
     
     
         12 . The stable pharmaceutical composition according to  claim 1 , wherein the composition is prepared by a process comprising the steps of:
 (a) mixing sitagliptin, at least one beneficial agent and optionally one or more pharmaceutically acceptable excipients;   (b) granulating the mixture of step (a) with or without a binder solution;   (c) blending granules obtained in step (b) with one or more pharmaceutically acceptable excipients; and   (d) compressing the blended granules into a tablet.   
     
     
         13 . The stable pharmaceutical composition according to  claim 1 , wherein the composition is prepared by a process comprising the steps of:
 (a) preparing solution or dispersion of sitagliptin, at least one beneficial agent and optionally one or more pharmaceutically acceptable excipients;   (b) spraying the solution or dispersion of sitagliptin on inert cores;   (c) blending coated cores obtained in step (b) with one or more pharmaceutically acceptable excipients; and   (d) compressing the blended granules into a tablet.   
     
     
         14 . The stable pharmaceutical composition according to  claim 1 , wherein the composition is prepared by a process comprising the steps of:
 (a) mixing sitagliptin and one or more pharmaceutically acceptable excipients; granulating the mixture with or without a binder solution to obtain the sitagliptin granules and optionally coating the granules;   (b) mixing at least one beneficial agent and one or more pharmaceutically acceptable excipients; granulating the mixture with or without a binder solution to obtain the granules and optionally coating the granules;   (c) blending granules obtained in step (a) and (b) with one or more pharmaceutically acceptable excipients; and   (d) compressing the blended granules into a tablet.   
     
     
         15 . The stable pharmaceutical composition according to  claim 1 , wherein the composition is prepared by a process comprising the steps of:
 (a) taking inert cores of sugar spheres;   (b) spraying solution or dispersion of sitagliptin and one or more pharmaceutically acceptable excipients;   (c) spraying solution or dispersion of at least one beneficial agent and one or more pharmaceutically acceptable excipients; and   (d) compressing the coated cores into a tablet.   
     
     
         16 . The stable pharmaceutical composition according to  claim 1 , wherein the composition is prepared by a process comprising the steps of:
 (a) preparing inert cores of at least one beneficial agent;   (b) seal coating of the cores of acid;   (c) spraying solution or dispersion of sitagliptin and one or more pharmaceutically acceptable excipients;   (d) drying the coated cores; and   (e) compressing the coated cores into a tablet.   
     
     
         17 . A stable pharmaceutical composition comprising sitagliptin and at least one beneficial agent, wherein the composition provides an in-vivo plasma profile for sitagliptin comprising:
 a mean of C max  from about 900 ng/mL to about 1000 ng/ml,   a mean of AUC from about 8000 ng*hr/mL to about 9000 ng*hr/mL; and   a mean of T max  at least about 2 hours.