Patent ID: 8470368

Claim:
A pharmaceutical dosage form having a first and second active drug, said dosage form comprising: (a) a controlled release core comprising: i) a core comprising at least one pharmaceutically acceptable excipient and only one active drug that consists of metformin hydrochloride; and ii) a sustained release coating surrounding the core; (b) optionally a first seal coating surrounding the sustained release coating that does not contain an active pharmaceutical ingredient and that rapidly disperses or dissolves in water; and (c) an immediate release pioglitazone layer surrounding the sustained release coating of the controlled release core or the first seal coating if present comprising: (i) pioglitazone hydrochloride; (ii) a binder selected from the group consisting of polyvinyl pyrrolidone, hydroxypropyl cellulose, hydroxyethylcellulose, hydroxypropyl methylcellulose, ethylcellulose, polymetharcylate, polyvinylalcohol, waxes and mixtures thereof; (iii) a pore forming agent selected from the group consisting of sodium chloride, potassium chloride, sucrose, sorbitol, mannitol, polyethylene glycols, propylene glycol and mixtures thereof; (iv) optionally a pharmaceutical excipient selected from the group consisting of absorption enhancers, plasticizers, antifoaming agent and combinations thereof wherein the immediate release pioglitazone layer is free of a surfactant and not less than 90%, of the pioglitazone hydrochloride is released from the dosage form within 45 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 after storage at 40° C. and 75% relative humidity for three months, the total Pioglitazone related compounds or impurities in the dosage form is not more than 0.6% as determined by high performance liquid chromatography and each individual pioglitazone related compound or impurity in the final dosage form is not more than 0.25% wherein the pioglitazone related compounds and impurities are: (i)(+/−)-5-[p-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl]-5-hydroxy-2,4-thiazolidinedione; (ii)(z)-5-[p-[2-(5-ethyl-2-pyridyl)ethoxy]benzylidene]-2,4-thiazolidinedione; (iii) (+/−)-5-[p-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl]-3-[2-(5-ethyl-2-pyridyl)ethyl]-2,4-thiazolidinedione; (iv) (+/−)-ethyl-2-carbamoyltio-3-[4-[2-(5-ethyl-2-pyridyl)ethoxy]phenyl-]propionate; and (v) ethyl-3-p-[2-(5-ethyl-2-pyridyl)ethoxy]phenyl-propionate.