PHARMACEUTICAL COMPOSITIONS
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.