DPP-IV inhibitor combined with a further antidiabetic agent, tablets comprising such formulations, their use and process for their preparation
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.
1. A solid pharmaceutical composition comprising or made from:
(a) 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine in a dosage range from about 0.5 mg to about 10 mg,
(b) metformin hydrochloride,
(c) a pharmaceutical excipient, and
(d) about 1 mg to 50 mg of L-arginine.
2. 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)-amino-piperidin-1-yl)-xanthine is present in a dosage strength of 0.5, 1, 2.5, 5, or 10 mg.
3. 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)-amino-piperidin-1-yl)-xanthine is present in a dosage strength of 2.5 mg.
4. The pharmaceutical composition according to claim 1 , wherein metformin hydrochloride is present in a dosage range from about 100 mg to about 1500 mg.
5. The pharmaceutical composition according to claim 1 , wherein metformin hydrochloride is present in a dosage strength of 250, 500, 625, 750, 850, or 1000 mg.
6. The pharmaceutical composition according to claim 1 , wherein metformin hydrochloride is present in a dosage strength of 500 mg, 850 mg, or 1000 mg.
7. 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)-amino-piperidin-1-yl)-xanthine and L-arginine are present in a weight ratio from about 1:20 to about 10:1.
8. The pharmaceutical composition according to claim 1 , wherein the excipient is selected from the group consisting of one or more fillers; a binder; a lubricant; and a glidant.
9. The pharmaceutical composition according to claim 1 , comprising copovidone as binder.
10. The pharmaceutical composition according to claim 9 , further comprising corn starch, magnesium stearate, or colloidal anhydrous silica.
11. The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition is a tablet selected from a mono-layer tablet, a bi-layer tablet, a press-coated tablet, and a tablet which is film-coated for drug-loading.
12. The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition is a tablet comprising a film-coat.
13. A solid pharmaceutical composition comprising or made from 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine in a dosage range from about 0.5 mg to about 10 mg, metformin hydrochloride, about 1 mg to 50 mg of L-arginine, a filler, a binder, a glidant, and a lubricant.
14. The pharmaceutical composition according to claim 1 , wherein 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine has a particle size distribution of X90<200 μm.
15. A pharmaceutical composition according to claim 1 made by a process comprising incorporating the active ingredients and about 1 mg to 50 mg of L-arginine in a pharmaceutical excipient selected from D-mannitol, corn starch, pregelatinized starch, copovidone, magnesium stearate, and colloidal anhydrous silica.
16. The pharmaceutical composition according to claim 1 , wherein the pharmaceutical excipient comprises a filler.
17. The pharmaceutical composition according to claim 1 , wherein the pharmaceutical excipient comprises a filler and a binder.
18. The pharmaceutical composition according to claim 1 , wherein the pharmaceutical excipient comprises a filler, a binder, and a lubricant.
19. The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition is a tablet comprising or made from:
(a) 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine in a dosage range from about 0.5 mg to about 10 mg,
(b) metformin hydrochloride,
(c) a pharmaceutical excipient, and
(d) about 1 mg to 50 mg of L-arginine.
20. The pharmaceutical composition according to claim 19 , wherein the pharmaceutical excipient comprises a filler.
21. The pharmaceutical composition according to claim 19 , wherein the pharmaceutical excipient comprises a filler and a binder.
22. The pharmaceutical composition according to claim 19 , wherein the pharmaceutical excipient comprises a filler, a binder, and lubricant.
23. The pharmaceutical composition according to claim 19 , wherein the pharmaceutical excipient comprises a filler, a binder, a lubricant, and a glidant.
24. The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition is a tablet comprising or made from:
(a) 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine in a dosage range from about 0.5 mg to about 10 mg,
(b) metformin hydrochloride,
(c) a pharmaceutical excipient comprising corn starch, copovidone, magnesium stearate, and colloidal anhydrous silica, and
(d) about 1 mg to 50 mg of L-arginine.
25. The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition is a tablet comprising or made from:
(a) 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine in a dosage of about 2.5 mg,
(b) about 0.5 mg to about 10 mg of metformin hydrochloride,
(c) a pharmaceutical excipient, and
(d) about 1 mg to about 25 mg of L-arginine.