IVIVC for Biopharmaceutical Classification System (BCS) Class II Drugs: Case Studies and Challenges

Abstract

In vitro–in vivo correlation (IVIVC) serves as a pivotal tool in drug development, enabling the prediction of in vivo drug performance based on in vitro dissolution data. This approach is particularly valuable for Biopharmaceutical Classification System (BCS) Class II drugs, which are characterized by low solubility and high permeability, making dissolution the rate-limiting step in absorption. Despite the theoretical suitability of IVIVC for this class, the practical application often presents significant challenges due to complex gastrointestinal dynamics and formulation-dependent variability. This article provides an in-depth review of IVIVC in the context of BCS Class II drugs, highlighting regulatory perspectives, technical hurdles, and formulation strategies. Through detailed case studies, ranging from successful correlations to partial or failed attempts, we explore the critical factors influencing the establishment of robust IVIVCs. Emerging approaches such as the use of biorelevant media, physiologically based pharmacokinetic (PBPK) modeling, and advanced in vitro systems are also discussed as potential solutions to current limitations. The insights presented aim to guide formulation scientists and regulatory professionals in navigating the complexities of IVIVC for BCS Class II compounds.