Best Practices for Integration of Dissolution Data into Physiologically Based Biopharmaceutics Models (PBBM): A Biopharmaceutics Modeling Scientist Perspective

Abstract

Dissolution is considered as a critical input into physiologically based biopharmaceutics models (PBBM)as it governs in vivo exposure. Despite many workshops, initiatives by academia, industry, and regulatory, wider practices are followed for dissolution data input into PBBM models. Due to variety of options available for dissolution data input into PBBM models, it is important to understand pros, cons, and best practices while using specific dissolution model. This present article attempts to summarize current understanding of various dissolution models and data inputs in PBBM software's and aims to discuss practical challenges and ways to overcome such scenarios. Different approaches to incorporate dissolution data for immediate, modified, and delayed release formulations are discussed in detail. Common challenges faced during fitting of z-factor are discussed along with novel approach of dissolution data incorporation using P-PSD model. Ways to incorporate dissolution data for MR formulations using Weibull and IVIVR approaches were portrayed with examples. Strategies to incorporate dissolution data for DR formulations wasdepicted along with practical aspects. Approaches to generate virtual dissolution profiles, using Weibullfunction, DDDPlus, and time scaling for defining dissolution safe space, and strategies to generate virtual dissolution profiles for justifying single and multiple dissolution specifications were discussed. Finally, novel ways to integrate dissolution data for complex products such as liposomes, data from complex dissolution systems, importance of precipitation, and bio-predictive ability of QC media for evaluation of CBA's impact were discussed. Overall, this article aims to provide an easy guide for biopharmaceutics modeling scientist to integrate dissolution data effectively into PBBM models.