Claims for Patent: 10,973,827

Summary for Patent: 10,973,827

Title:	DPP-IV inhibitor combined with a further antidiabetic agent, tablets comprising such formulations, their use and process for their preparation
Abstract:	The present invention relates to pharmaceutical compositions comprising fixed dose combinations of a DPP-4 inhibitor drug and a partner drug, processes for the preparation thereof, and their use to treat certain diseases.
Inventor(s):	Friedl; Thomas (Ochsenhausen, DE), Braun; Michael (Senden, DE), Egusa; Kenji (Biberach an der Riss, DE), Fujita; Hikaru (Osaka, JP), Maruyama; Megumi (Hyogo, JP), Nishioka; Takaaki (Kobe, JP)
Assignee:	Boehringer Ingelheim International GmbH (Ingelheim am Rhein, DE)
Application Number:	16/676,643
Patent Claims:	1. A pharmaceutical composition comprising 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-a- mino-piperidin-1-yl)-xanthine in a dosage of 2.5 mg or 5 mg, metformin hydrochloride, and a basic amino acid having an intramolecular amino group and alkaline characteristics in an amount sufficient to suppress degradation of said 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-a- mino-piperidin-1-yl)-xanthine, wherein the pharmaceutical composition is in the form of a tablet comprising a film-coat, which film-coated tablet comprises the following amounts (% by weight of total coated tablet mass): 0.1-0.5% of 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R) amino-piperidin-1-yl)-xanthine, 47-85% of metformin HCl, 0.07-2.2% of L-arginine as the basic amino acid, 3.9-8.1% of a binder, 2.3-5.9% of a first filler, 0-4.4% of a second filler, 0-33% of a third filler, 0.7-1.5% of a lubricant, and 0.1-0.5% of a glidant. 2. The pharmaceutical composition according to claim 1, wherein the metformin hydrochloride is present in a dosage range from about 100 mg to about 1500 mg; or wherein the metformin hydrochloride is present in a dosage strength of 250, 500, 625, 750, 850 or 1000 mg; or wherein the metformin hydrochloride is present in a dosage strength of 500 mg, 850 mg or 1000 mg. 3. The pharmaceutical composition according to claim 1, wherein L-arginine is present from about 1 mg to about 50 mg, or from about 1 mg to about 25 mg. 4. The pharmaceutical composition according to claim 1, wherein the 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-a- mino-piperidin-1-yl)-xanthine and L-arginine are present in a weight ratio from about 1:20 to about 10:1, or from about 1:15 to about 10:1, or from about 1:10 to about 10:1. 5. The pharmaceutical composition according to claim 1, wherein: the first, second and third fillers are selected from the group consisting of D-mannitol, corn starch and pregelatinized starch; the binder is copovidone; the lubricant is magnesium stearate; and the glidant is colloidal anhydrous silica. 6. The pharmaceutical composition according to claim 1; wherein the film-coated tablet is selected from the group consisting of a mono-layer tablet, a bi-layer tablet, a press-coated tablet, and a tablet which is film-coated for drug-loading. 7. The pharmaceutical composition according to claim 1, wherein the film-coat comprises: a film-coating agent; a plasticizer; optionally a glidant, and optionally one or more pigments. 8. The pharmaceutical composition according to claim 1, wherein the film-coated tablet is a mono-layer tablet. 9. The pharmaceutical composition according to claim 1, which is an immediate release dosage form, characterized in that in a dissolution test after 45 minutes at least 75% by weight of each of 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-a- mino-piperidin-1-yl)-xanthine and metformin is dissolved. 10. The pharmaceutical composition according to claim 8 wherein: the percentage of metformin hydrochloride is about 85% by weight of total tablet core, the amount of 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-a- mino-piperidin-1-yl)-xanthine is about 0.2%-0.4% by weight of total tablet core, the amount of L-arginine is about 2% by weight of total tablet core, the tablet crushing strength is higher than or equal to 100 N, the tablet friability is lower than or equal to 0.5%, the tablet thickness is from about 5.7 to about 8.4 mm, the tablet core weight is from about 590 to about 1180 mg, and/or the tablet disintegration time is lower than or equal 15 min.