Novel pharmaceutical formulation containing a biguanide and a thiazolidinedione derivative

摘要

Disclosed is a pharmaceutical dosage form comprising: (A) a controlled release osmotic tablet core comprising metformin hydrochloride that exhibits the following dissolution profile when tested in a USP Type 2 apparatus at 75 rpms in 900 ml of simulated intestinal with a pH of7.5 and at 37 degrees C: 0-25 wt% of the metformin hydrochloride is released after 2 hours; 10-45 wt% of the metformin hydrochloride is released after 4 hours; 30-90 wt% of the metformin hydrochloride is released after 8 hours; not less than 50 wt% of the metformin hydrochloride is released after 12 hours; not less than 60 wt% of the metformin hydrochloride is released after 16 hours; and not less than 70 wt% of the metformin hydrochloride is released after 20 hours; and (B) an immediate release pioglitazone hydrochloride layer surrounding the osmotic tablet that releases not less than 90 wt% of the pioglitazone hydrochloride from the dosage form within 30 minutes when tested according to the United States Pharmacopeia (USP) 26, with Apparatus 1 at 100 rpm, 37degrees C and 900 ml of 0.3 M KCI-HCl Buffer, pH 2.0 and the dosage form contains not more than 0.25 wt% of the following compounds: (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-pyridyI)ethoxy]phenyI-propionate. (62) Divided Out of 545653