Biopharmaceutical evaluation of formulated metformin/rosiglitazone tablets

The study aimed to combine two antidiabetic agents with different mechanisms of action, namely, metformin HCl and rosiglitazone maleate, in a tablet to improve glycemic control in patients with type II diabetes. The preformulation study started with development and validation of an HPLC method for the determination of both drugs in the mixture. The results of visual inspection, TLC, DSC, and FT-IR verified the absence of any physical or chemical interaction between both compounds. Four compatible excipients were selected for the formulation of the tablets by wet granulation according to a 2(2) factorial design. The prepared tablet blends were acceptable in terms of the modal size of particle distribution, bulk density, Hausner's ratio, Carr's index, and flowability. All formulations fulfilled the pharmacopoeial specifications for weight variation, content uniformity, friability, and hardness. They released 100% of the drug during the first 45 min, displaying higher dissolution efficiency than commercially available Rosiplus tablets. The tablet formulation that passed the physical and chemical stability study for 24 months at ambient conditions was tested in vivo on healthy volunteers in a cross-over design. Statistical analysis proved that the prepared tablets were bioequivalent to the commercial ones in terms of both the rate and the extent of absorption.