DPP-IV inhibitor combined with a further antidiabetic agent, tablets comprising such formulations, their use and process for their preparation

A stable pharmaceutical composition comprising a dipeptidyl peptidase-4 (DPP-4) inhibitor which is 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine free base, a partner drug which is metformin hydrochloride, one or more pharmaceutical excipients, and a stabilizing agent for stabilizing said DPP-4 inhibitor against degradation to form an impurity and/or degradation product caused by reaction of the primary amino group of 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine free base when combined with metformin hydrochloride in the composition;

• wherein the stabilizing agent is a nucleophilic and/or basic agent or a buffering agent that is a basic amino acid having an intramolecular amino group and alkaline characteristics;
• wherein the pharmaceutical composition is bioequivalent to the free combination of the DPP-4 inhibitor and metformin hydrochloride;
• wherein the DPP-4 inhibitor is present in a dosage range from 0.5 mg to 10 mg, and the stabilizing agent is present in an amount minimized to not alter the bioequivalence of the pharmaceutical composition to the free combination but sufficient to stabilize said DPP-4 inhibitor against degradation, and
• wherein the impurity and/or degradation product is an N-acetyl or N-carbamoyl derivative of the free base DPP-4 inhibitor.