Establishing the Dissolution Bioequivalence Safe Space for Immediate Release Formulation of Baclofen using Physiologically based Biopharmaceutics Modeling

Abstract

Clinical bioequivalence assessment is one of the critical aspects in the product development, since these studies are helpful in establishing the equivalence between a generic product and its reference-listed drug as per regulatory requirements. Physiologically based biopharmaceutics modeling (PBBM) can be a useful tool to assess potential bioequivalence risks and predict the outcome of bioequivalence studies. 2. In this study, GastroPlus® was used for virtual bioequivalence (BE) assessments, which required defining a clinically relevant dissolution safe space for Baclofen Tablets 20 mg USP. The purpose was to investigate if bioequivalence can be achieved in silico with the help of a PBB model developed using in-house in vitro and in vivo data. This study successfully predicted the pharmacokinetics of the theoretically slower dissolving batch compared with the pivotal test and reference formulations. 3. Ultimately, if there is confidence in such models, they can be used as a biowaiver approach for different products. Systemically applying these models to set clinically relevant specifications can greatly reduce product development timelines and costs, minimize drug exposure to healthy volunteers, and ensure product quality.