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 such as gastric emptying, pH, bile salt concentrations etc. Coupled to this is the necessity for appropriate mechanistic models to capture the complexities of the interplay between solubilisation, dissolution, and gut wall permeation. This requires both understanding of mechanisms involved and a means to obtain the required parameters. For example, the latter can be done through modeling appropriate in vitro experiments although this is a developing area with respect to complex drug products containing multiple interacting excipients.
In this webinar, we will provide 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. Examples of the application of some of these tools will be provided.
About Our Speakers
David B. Turner PhD is a Senior Principal Scientist at Certara UK Limited (Simcyp Division) with a focus on the physico-chemical aspects of PBPK modelling and is the lead scientist for oral drug absorption. David is currently the PI for a FDA grant to develop modeling tools for handling supersaturating drug products. He has a Biochemistry BSc, a Computer Science MSc and a PhD in Chemoinformatics and QSAR modelling. Prior to joining Certara in 2004 he worked in a Computational Chemistry Group (Syntem SA, Nîmes, France) focused mainly upon high throughput in silico discovery and virtual screening projects. He is author or co-author on 29 peer-reviewed papers.