Assessing the in vitro dissolution rate of metformin from different commercially available tablets using distinct physiological pH media at different fast/fed states.

Abstract

Diabetes is a chronic metabolic disorder characterized by uncontrolled blood sugar, where the body cannot produce enough insulin to compensate high blood sugar in the body. Metformin is considered first drug for type 2 diabetes in the guidelines, and is available under different brands. These brands must exhibit similar levels of dissolution-derived bioavailability under the same conditions. Hence, comparing the in vitro dissolution rate of different generic metformin brands, including Diabex, Metex, and Apo-metformin, all of which contain 500 mg of metformin in an extended-release formulation and have been approved as interchangeable generics by the FDA and the TGA. An in vitro dissolution test was conducted at different pH levels, namely 2.4, 6.8, and 7.4. Furthermore, the tablets were immersed in 900 ml of media with varying viscosity levels achieved by manipulating the hydroxypropyl methylcellulose (HPMC) concentration. The results revealed that all brands exhibited a reduced release of metformin under acidic pH conditions compared to alkaline conditions, where all brands demonstrated similar behaviour. Additionally, the release of metformin from the same brand in alkaline pH showed insignificant changes at different media viscosities. However, at pH 6.8 in an aqueous solution, there was a significant variation in the release of metformin between Apo-metformin and Diabex, the original brand. These findings suggest a deviation in the release profile of the active ingredient, which could be attributed to the use of different excipients in the matrix as part of the delivery system. Based on these results, it is recommended to conduct further fundamental in vitro analyses before proceeding to in vivo studies. These additional analyses are crucial for better understanding the behaviour and performance of the different generic metformin brands, particularly in terms of their drug release profiles.