Updates to the Simcyp Simulator’s Oral Absorption ADAM and M-ADAM Models

Predicting the rate and extent of absorption of orally dosed drug products is critical to developing new and generic drug products. Powerful tools such as the Simcyp Population-based PBPK Simulator have been developed to simulate both the average subject and the population variability of PK endpoints. The Simulator includes complex multi-compartment descriptions of the gastrointestinal tract— the Advanced, Dissolution, Absorption and Metabolism (ADAM) or Multi-layer gut wall ADAM (M-ADAM) models. In particular, there is increasing emphasis on the potential of virtual bioequivalence (VBE) to guide or waive the need for clinical bioequivalence trials, which may be required due to formulation manufacturing change, during SUPAC (scale-up and post-approval changes), etc. Reaching the full potential of VBE simulations requires knowing the between and within subject variability of physiological parameters.

In this webinar, we provided an update on the extensive recent additions to the mechanistic models for handling oral dosage forms available within the ADAM/M-ADAM framework, which include a particle population balance (PPB) model, dual solid state (polymorph) handling, excipient binding, a nucleation model, a dynamic bile salt model, and mechanistic models for handling pharmaceutical salts.