In vitro + In Silico: Advanced Tools for Absorption Prediction

A large fraction of chemical entities entering original or generic development fall into BCS Class II or IV, where low solubility and dissolution rate often limit oral bioavailability. To overcome these barriers, advanced formulation strategies such as amorphous solid dispersions, lipid-based delivery systems, and nanonization have become well-established approaches to increase apparent solubility and enhance absorption; however, they also introduce new complexities.
To characterize and optimize these advanced formulations, dissolution-permeation (also known as flux) devices are widely used in pre-formulation and formulation development, enabling the simultaneous assessment of dissolution and permeation across a membrane, thereby providing insight into both drug release and absorption potential.
Further combining experimental flux results with physiologically relevant mechanistic modelling, it is possible to identify the rate-limiting steps of absorption, account for the particle drift of colloidal species and nanoparticles, and bridge the gap between in vitro measurements and in vivo pharmacokinetics. This in vitro + in silico approach not only refines rank-ordering but also allows quantitative prediction of absorption rates and pharmacokinetic profiles across preclinical species and humans. Ultimately, this integration enhances formulation selection, reduces development risk, and accelerates the path toward clinical evaluation.
In this presentation, we will:
1) Provide an overview of dissolution-permeation (flux) assays and demonstrate their validation as predictive tools for in vivo absorption when combined with mechanistic modelling.
2) Present case studies characterizing and comparing amorphous solid dispersions, nanoparticle formulations, and lipid-based formulations.
3) Show examples of in vivo absorption rate and PK profile predictions across multiple species, illustrating the translational value of the methodology