In vitro and in Silico Modeling for Amorphous Solid Dispersions

This would be the fourth presentation related to the amorphous solid dispersion (ASD) 2h-symposium. PBPK modeling is gaining a lot of interest in industry and regulatory context as decisions can be made based on simulations representing virtual populations. This presentation will provide an overview of where physiologically based biopharmaceutics modelling (PBBM) for oral drug product design is positioned in the wider landscape of model-informed drug development. The drivers and opportunities for adopting model-based approaches to inform bioperformance of oral formulations will be discussed and the impact of recent regulatory guidance for application of PBBM for product development and control strategies will be considered. The presentation will also include a case study to exemplify the value in combining in vitro characterisation data with an in silico PBBM model to predict formulation performance. The case study assesses how data from in vitro and in silico models can be integrated to guide the formulation design of an amorphous solid dispersion for a poorly soluble model compound (atazanavir). The case study will also describe how the PBBM model can be used to evaluate the biorelevance of the in vitro dissolution techniques used to characterise the solid dispersion. The presentation will summarise how PBBM can be used to inform the biopharmaceutics risk assessment for the drug product and define a safe space / target dissolution range for formulation prototypes which will maintain predicted PK performance.