Comparison of dissolution profiles and apparent permeabilities of commercially available metformin hydrochloride tablets in Turkey

Abstract

The purpose of this study was to evaluate the similarity of dissolution and permeability properties of commercially available immediate-release metformin hydrochloride (MH) tablets (1000 mg strength) including five generic products obtained from the Turkish drug market (tablets A–E) and two reference products (obtained from the Turkish and European markets). In vitro dissolution studies were conducted in accordance with the MH tablet monograph in the USP (1000 mL, 75 rpm) and with the BCS-based biowaiver guidance in three different media (pH 1.2, pH 4.5, and pH 6.8; 900 mL, 50 rpm). The apparent permeability of MH in all tablets and raw MH was determined in Caco-2 cells. Dissolution studies revealed that neither the generics (except generic tablet B) nor the reference tablets fulfilled the criteria for very rapid dissolution. Although the dissolution profiles of the reference tablets were similar (f2 > 50), none of the generic tablets were similar to either of the reference tablets. Permeability of MH for all reference and generic tablet formulations was similar to that of raw MH (p > 0.05). In contrast, a significant difference in permeability was observed between the two reference tablets (p < 0.05), and only one generic tablet (A) had permeability similar to both reference tablets. As MH has low permeability, potential alterations in permeability due to the dosage form can affect its bioavailability. The results of this study indicate that immediate-release MH tablets do not meet the criteria for very rapid dissolution for the BCS-based biowaiver.