Pharmaceutical formulation containing a biguanide and a thiazolidinedione derivative
View Patent ↗A pharmaceutical dosage form comprising a controlled release component comprising an antihyperglycemic drug in combination with a second component comprising a thiazolidinedione derivative and a disintegrating agent is herein disclosed and described. The dosage formulation exhibits a significant increase in bioavailability of the thiazolidinedione derivative component compared to conventional immediate release dosage forms containing only a thiazolidinedione derivative.
1. A pharmaceutical dosage form comprising:
(a) a controlled release core comprising metformin hydrochloride and at least one pharmaceutically acceptable excipient; and
(b) an immediate release pioglitazone layer applied to the controlled release metformin core wherein the immediate release pioglitazone layer comprises:
(i) pioglitazone hydrochloride;
(ii) a binder;
(iii) about 1 to about 15% based upon the total weight of the pioglitazone layer of a poloxamer; and
(iv) about 5 to about 30% based upon the total weight of the pioglitazone layer of sodium starch glycolate; and
wherein not less than 95% of the pioglitazone is released from the dosage form within 30 minutes when tested according to the United States Pharmacopeia (USP) 26, with Apparatus 1 at 100 rpm, 37° C. and 900 ml of 0.3 M KCl—HCl Buffer, pH 2.0; and
wherein the dosage form exhibits a C max for the pioglitazone that is at least 130% of the C max for an immediate release pioglitazone tablet containing the same amount of pioglitazone as present in the immediate release pioglitazone layer, and an AUC for the pioglitazone that is at least 115% of the AUC for the immediate release pioglitazone tablet.
2. The pharmaceutical dosage form as defined in claim 1 wherein the poloxamer comprises about 5 to about 12% of the total weight of the pioglitazone layer and the sodium starch glycolate comprises about 10 to about 20% of the total weight of the pioglitazone layer.
3. The pharmaceutical dosage form as described in claim 1 wherein the dosage form exhibits a C max for the pioglitazone that is at least 135% of the C max for the immediate release pioglitazone tablet.
4. The pharmaceutical dosage form as described in claim 1 wherein the dosage form exhibits an AUC for the pioglitazone that is at least 120% of the AUC for the immediate release pioglitazone tablet.