uFlux In Vitro-In Vivo Correlation (IVIVC) Testing Trans-Membrane Permeation And BSC Class II Formulation Challenges

A previous design of experiments (DoE) was used to developed a generic BSC Class II suspension utilizing a fiber optic probe (FO) monitoring system via regression analysis. DoE and regression analysis provided a generic formulation which matched dissolution profile, USP Assay, and physical characteristics (XRPD, Particle Size, and Rheology) of the reference listed drug (RLD).

However, when the bioequivalence (BE) study was conducted the generic outperformed the RLD having increased bioavailability (BA) by ~1.5 times greater. The difference in BE may have occurred due to changes in the concentration of excipients that are difficult or cannot be quantified with consistency, accuracy, or relevance.

Our focus turned to methods that could discriminate against formulation differences which may not present using traditional in vitro dissolution techniques. The uFlux side by side cell monitors in vitro transport across a membrane that is a model for gastrointestinal in vivo absorption (GIT 0), Figure 1. The uFlux provides real time monitoring of dissolution and equilibrium Flux (∂c/∂t) to provide IVIVC testing. Herein we demonstrate the challenges to develop an equivalent BCS class II suspension.