Investigating a Modified Apparatus to Discriminate the Dissolution Capacity InVitro and Establish an IVIVC of Mycophenolate Mofetil Tablets in the Fed State.

Abstract

In this study, a modified dissolution apparatus was developed by equipping a USP apparatus Ⅰ with an open-loop system to discriminate the dissolution capacity invitro and establish an invitro and invivo correlation (IVIVC) for mycophenolate mofetil (MMF) tablets. MMF had strong pH-dependent solubility that could influence the dissolution rate invivo after the meal. Dissolution tests involving reference (Cellcept®) and test formulations (F1 and F2) were conducted using pH 4.5 acetate buffer to simulate gastric fluids in the fed state. The dissolution profiles of the reference and test formulations were distinguished by using the modified dissolution apparatus and compared with those determined using the USP apparatuses Ⅱ and Ⅳ, and the dissolution capacities of the formulations were discriminated at different sampling time-points. The results of human bioequivalence (BE) studies in the fed state were consistent with invitro evaluations that the maximum concentrations (Cmax,invivo) of both F1 and F2 fell below the acceptable range (80.00%). A level A IVIVC between the absorption fraction invivo and dissolution invitro, and a level C correlation between Cmax,invivo and Cmax,invitro, were established to guide the optimization of the tablet formulation containing MMF.