COMPARATIVE EVALUATION OF IN VITRO BIOEQUIVALENCE OF METFORMIN HYDROCHLORIDE IN SOME TABLET FORMULATIONS

ABSTRACT Metformin hydrochloride is a widely prescribed oral hypoglycemic agent used in the management of type 2 diabetes mellitus. Metformin is available in various formulations including immediate release and extended-release tablets. Ensuring the bioequivalence of these formulations is essential for guaranteeing therapeutic efficacy and patient safety. In vitro bioequivalence assessments play an important role in the development and evaluation of generic metformin products. This study involved comparing the dissolution profiles of six different brands (including the innovator brand) of metformin hydrochloride tablets under biowaiver conditions in three dissolution media. Quality control tests were also carried out on all six brands and they include tablet hardness, friability, disintegration, weight uniformity, assay and content uniformity. A developed Spectrophotometric method for determination of metformin hydrochloride in distilled water was found to be linear in the range of 0.2 - 1.0 mg/mL. The regression equation of the calibration graph and correlation coefficient was found to be y = 0.9482x - 0.0332 and 0.9978. Dissolution testing under biowaiver conditions showed different results. All tablets of the generics and innovator brand were able to dissolve by more than 80 % within 30 min. Three brands were bioequivalent to the innovator brand having f2 ≥ 50 in the three-dissolution media. The remaining two brands showed variable results. All the brands met the standard for disintegration as they all disintegrated within 15 minutes and that for the weight uniformity test as they had percentage deviation less than 5 %. Two brands failed the friability test as they had percentage weight loss greater than 1 %. Four brands also failed the hardness test as two brands were found to have a crushing strength of less than 5 kg/N while two brands had crushing strength of more than 8 kg/N. All brands showed assay values within the monograph specification (95 % - 105 %) while two brands were out of the specified limit (95 % -105 %) for content uniformity. Generics of metformin hydrochloride varied in their bio-equivalence to the innovator brand. This variation could be explained by different excipients, and manufacturing conditions. In vivo bioequivalence testing should be conducted to confirm that the innovator could be safely interchangeable with the brand and this variation won’t affect the safety and efficacy of the drug.