Pharmaceutical compositions

Abstract

The present invention relates to pharmaceutical compositions comprising fixed dose combinations of a DPP-4 inhibitor drug and/or a SGLT-2 inhibitor drug, and metformin XR, processes for the preparation thereof, and their use to treat certain diseases.

1 . A pharmaceutical composition comprising
 a) an inner extended release core comprising metformin or metformin hydrochloride and one or more excipients;   b) an optional intermediate seal coating; and   c) an outer immediate release coating comprising at least one active pharmaceutical ingredient selected from a DPP-4 inhibitor and a SGLT-2 inhibitor, and one or more excipients.   
     
     
         2 . The pharmaceutical composition according to  claim 1 , wherein the inner extended release core a) is a formulation comprising metformin hydrochloride, a swellable and/or extended release polymer, and one or more further excipients. 
     
     
         3 . The pharmaceutical composition according to  claim 1 , wherein the outer immediate release coating c) is a film coat formulation comprising linagliptin, L-arginine as stabilizer, a film-coating agent, a plasticizer, and, optionally, a glidant. 
     
     
         4 . The pharmaceutical composition according to  claim 3 , wherein the weight ratio of the L-arginine to linagliptin is within the range from about 2:1 to about 1:1, or up to about 0.2:1. 
     
     
         5 . The pharmaceutical composition according to  claim 1 , wherein the outer immediate release coating c) is a film coat formulation comprising 1-chloro-4-(β-D-glucopyranos-1-yl)-2-[4-((S)-tetrahydrofuran-3-yloxy)-benzyl]-benzene, a film-coating agent, a plasticizer, and, optionally, a glidant. 
     
     
         6 . The pharmaceutical composition according to  claim 3 , wherein the film-coating agent is hydroxypropyl methylcellulose, e.g. Hypromellose 2910, Methocel E5, or Methocel E15. 
     
     
         7 . The pharmaceutical composition according to  claim 5 , wherein the film-coating agent is hydroxypropyl methylcellulose, e.g. Hypromellose 2910, Methocel E5, or Methocel E15. 
     
     
         8 . The pharmaceutical composition according to  claim 3 , wherein the plastizicer is polyethylene glycol, e.g. Macrogol 400, 6000 or 8000. 
     
     
         9 . The pharmaceutical composition according to  claim 5 , wherein the plastizicer is polyethylene glycol, e.g. Macrogol 400, 6000 or 8000. 
     
     
         10 . The pharmaceutical composition according to  claim 3 , wherein the plastizicer is propylene glycol. 
     
     
         11 . The pharmaceutical composition according to  claim 5 , wherein the plastizicer is propylene glycol 
     
     
         12 . The pharmaceutical composition according to  claim 3 , wherein the optional glidant is talc. 
     
     
         13 . The pharmaceutical composition according to  claim 5 , wherein the optional glidant is talc. 
     
     
         14 . The pharmaceutical composition according to  claim 1  wherein the seal coating is present. 
     
     
         15 . The pharmaceutical composition according to  claim 14 , wherein the seal coating comprises a film-coating agent, a plasticizer, and, optionally, a glidant, one or more pigments and/or colors. 
     
     
         16 . The pharmaceutical composition according to  claim 1 , wherein the seal coating is absent. 
     
     
         17 . The pharmaceutical composition according to  claim 1 , wherein the metformin hydrochloride is present in a unit dosage strength of 500, 750, 850, 1000 or 1500 mg. 
     
     
         18 . The pharmaceutical composition according to  claim 1 , wherein the DPP-4 inhibitor is linagliptin and is present in a unit dosage strength of 0.5, 1, 2.5 or 5 mg. 
     
     
         19 . The pharmaceutical composition according to  claim 1 , wherein the SGLT-2 inhibitor is 1-chloro-4-(β-D-glucopyranos-1-yl)-2-[4-((S)-tetrahydrofuran-3-yloxy)-benzyl]-benzene and is present in a unit dosage strength of 5, 10, 12.5 or 25 mg. 
     
     
         20 . The pharmaceutical composition according to  claim 1 , which is a tablet for oral administration. 
     
     
         21 . The tablet according to  claim 20  further comprising an outer film over-coat. 
     
     
         22 . The tablet according to  claim 21 , wherein the outer film over-coat comprises a film-coating agent, a plasticizer, and, optionally, a glidant, one or more pigments and/or colors. 
     
     
         23 . A method of using the pharmaceutical composition according to  claim 1  for treating, preventing, slowing the progression, or delaying the onset of metabolic diseases either in type 2 diabetes patients who have not been previously treated with an antihyperglycemic agent,
 or in type 2 diabetes patients with insufficient glycemic control despite therapy with one or two conventional antihyperglycemic agents selected from metformin, sulphonylureas, thiazolidinediones, glinides, alpha-glucosidase blockers, GLP-1 or GLP-1 analogues, and insulin or insulin analogues. 
 
     
     
         24 . The method of  claim 23 , wherein the metabolic disease is type 2 diabetes mellitus and conditions related thereto. 
     
     
         25 . The method of  claim 23 , wherein the DPP-4 inhibitor is linagliptin and the SGLT-2 inhibitor is 1-chloro-4-(β-D-glucopyranos-1-yl)-2-[4-((S)-tetrahydrofuran-3-yloxy)-benzyl]-benzene. 
     
     
         26 . A pharmaceutical composition comprising
 a) an inner extended release core comprising metformin hydrochloride and one or more excipients;   b) an optional intermediate seal coating; and   c) an outer immediate release coating comprising at least one active pharmaceutical ingredient selected from linagliptin, and 1-chloro-4-(β-D-glucopyranos-1-yl)-2-[4-((S)-tetrahydrofuran-3-yloxy)-benzyl]-benzene, and one or more excipients.   
     
     
         27 . The pharmaceutical composition according to  claim 26  which is a tablet for oral administration.