Use of In vitro Dissolution Testing to Assess Multiple Generic Metformin Tablets

Abstract

Aims: Metformin is a high-solubility and low-permeability drug that is widely used as an oral anti-diabetic medication. In many countries, metformin is available as multiple generic formulations, with over 10 registered products, which are approved to be dispensed interchangeable. The aims of this study were to assess the in vitro dissolution profiles of a range of commercial brands of metformin hydrochloride tablets under a range of in vitro conditions and to determine whether differences in in vitro dissolution can be detected under a range of conditions. Methodology: Single and multiple (2 or 4) tablets from all brands were tested in both pH 6.8 and 0.1M HCl (gastric pH) dissolution medium and collected samples were analysed by high-performance liquid chromatography. Results: At least three distinct dissolution profiles were seen, designated slow, medium and fast released profiles. The innovator product, Glucophage® exhibited a medium released profile while Glucohexal® (G1) and Diaformin® (G3) displayed a fast released and a slow released profile respectively. The differences in the dissolution profiles were more apparent in the 0.1M HCl medium and a higher degree of disparity between the dissolution profiles was observed when the number of tablets in each dissolution flask increased. Conclusion: The results indicated that multiple registered versions of metformin have different dissolution profiles that can be detected even under standard in vitro conditions. However, all formulations were extensively dissolved within 45 minutes, suggesting that the in vivo performance of the different brands are not likely to differ to a clinically significant extent.