Pharmaceutical composition and uses thereof

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 hydrochloride and one or more excipients;   b) an optional seal and/or barrier coating; and   c) an immediate release coating comprising 1-chloro-4-(β-D-glucopyranos-1-yl)-2-[4-((S)-tetrahydrofuran-3-yloxy)-benzyl]-benzene and one or more excipients.   
     
     
         2 . The pharmaceutical composition according to  claim 1 , wherein the inner extended release core a) comprises metformin hydrochloride, a swellable and/or extended release polymer, and one or more further excipients. 
     
     
         3 . The pharmaceutical composition according to  claim 1 , further comprising a film-coating agent, a plasticizer, and, optionally, a glidant. 
     
     
         4 . The pharmaceutical composition according to  claim 1 , wherein the seal coating is present and/or the barrier coating is present. 
     
     
         5 . The pharmaceutical composition according to  claim 4 , wherein the seal and/or barrier coating is each a film coat formulation independently comprising:
 one or more film-coating agents selected from hydroxypropyl methylcellulose (HPMC), polyvinyl alcohol (PVA), ethyl cellulose, hydroxypropyl cellulose, polydextrose, methacrylic and/or acrylic polymer, or a mixture thereof,   optionally one or more plasticizers selected from polyethylene glycol, propylene glycol, diethyl phthalate, tributyl sebacate and/or triacetin, or a mixture thereof,   optionally a glidant selected from talc, magnesium stearate and fumed silica, and optionally one or more pigments and/or colorants.   
     
     
         6 . The pharmaceutical composition according to  claim 4 , wherein the seal and/or barrier coating is each a film coat formulation independently comprising a film-coating agent, a plasticizer, and, optionally, a glidant, one or more pigments and/or colors. 
     
     
         7 . The pharmaceutical composition according to  claim 4 , wherein the seal and/or barrier coat comprises:
 a film-coating agent which is hydroxypropyl methylcellulose (HPMC),   a plasticizer which is triacetin,   a glidant which is talc, and   optionally one or more pigments and/or colors.   
     
     
         8 . The pharmaceutical composition according to  claim 4 , wherein the seal and/or barrier coat comprises:
 one or more film-coating agents selected from the group consisting of hydroxypropyl methylcellulose (HPMC) and polydextrose, or mixtures thereof,   a plasticizer selected from polyethylene glycol, and   optionally one or more pigments and/or colors.   
     
     
         9 . The pharmaceutical composition according to  claim 4 , wherein the seal and/or barrier coat comprises:
 a mixture of one or more hydroxypropyl methylcellulose and polydextrose,   a plasticizer which is polyethylene glycol 8000, and   optionally one or more pigments (and/or colors.   
     
     
         10 . 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. 
     
     
         11 . The pharmaceutical composition according to  claim 1 , wherein b) is present and is a barrier coating comprising or consisting essentially of polydextrose, hydroxypropyl methylcelluloses, titanium dioxide and polyethylene glycol, and wherein
 the barrier coating has a weight in the range from 50 to 100 mg, or   the barrier coating has a weight of or 68 mg or 85 mg.   
     
     
         12 . The pharmaceutical composition according to  claim 1 , wherein the 1-chloro-4-(β-D-glucopyranos-1-yl)-2-[4-((S)-tetrahydrofuran-3-yloxy)-benzyl]-benzene is present in a unit dosage strength of 5, 10, 12.5 or 25 mg. 
     
     
         13 . The pharmaceutical composition according to  claim 1 , wherein said pharmaceutical composition is a tablet for oral administration. 
     
     
         14 . The pharmaceutical composition according to  claim 13  further comprising a color and/or final coating. 
     
     
         15 . The pharmaceutical composition according to  claim 14 , wherein the color and/or final coating is each a film coat formulation independently comprising:
 one or more film-coating agents selected from hydroxypropyl methylcellulose (HPMC), polyvinyl alcohol (PVA), ethyl cellulose, hydroxypropyl cellulose, polydextrose, methacrylic and/or acrylic polymer, or a mixture thereof,   optionally one or more plasticizers selected from polyethylene glycol, propylene glycol, diethyl phthalate, tributyl sebacate and/or triacetin, or a mixture thereof,   optionally a glidant selected from talc, magnesium stearate and fumed silica, and   optionally one or more pigments (e.g. titanium dioxide) and/or colorants.   
     
     
         16 . The pharmaceutical composition according to  claim 14 , wherein the color and/or final coating is each a film coat formulation independently comprising a film-coating agent, a plasticizer, and, optionally, a glidant, one or more pigments and/or colors. 
     
     
         17 . A method of treating and/or preventing (including slowing the progression and/or delaying the onset) of metabolic diseases, especially type 2 diabetes mellitus and conditions related thereto (e.g. diabetic complications) comprising administering a pharmaceutical composition according to  claim 1 :
 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.