Studies in formulation development and evaluation of floating drug delivery system of metformin HCL

Abstract

The purpose of this investigation was to prepare a gastro-retentive drug delivery system for metformin hydrochloride, which is incompletely absorbed from the small intestine because of narrow absorption window. Effervescent based approach was used for the development of the formulation. Sodium bicarbonate was incorporated as a gas-generating agent. The effects of amount of HPMC and carbopol on drug release profile and floating properties were investigated. The addition of carbopol reduces the drug dissolution due to its low water uptake property. A central composite design was applied to systematically optimize the drug release. The amount of HPMC (X1) and carbopol (X2) were selected as independent variables. The floating lag time, time required for 50% (t50) and 80% drug dissolution (t80) were selected as dependent variables. The results of the central composite design indicated that amount of HPMC favors sustained release of metformin hydrochloride from a gastro-retentive formulation. A theoretical dissolution profile was generated using pharmacokinetic parameters of metformin hydrochloride. The similarity factor f2 was applied to compare the central composite design batches and the theoretical dissolution profile. Batches F7, F8 and F9-13 (replicate batches) were promising batches as the f2 values were greater than 50. The in-vivo X-ray studies showed that the tablet was intact and remained floated in the gastric content up to 6 hr after administration.