Product Performance Models in Vivo and Applications from Pre-POC to Phase 3 and Beyond

Modeling and simulation of drug dissolution and oral absorption has been increasingly used over the last decade to understand drug behavior in vivo based on the physicochemical properties of Active Pharmaceutical Ingredients (API) and dosage forms. As in silico and in vitro tools become more sophisticated and our knowledge of physiological processes has grown, model simulations can provide a valuable confluence, tying-in in vitro data with in vivo data while offering mechanistic insights into clinical performance. To a formulation scientist, this unveils not just the parameters that are predicted to significantly impact product performance (dissolution/absorption), but helps address specific in vivo mechanisms. In developing a new chemical entity (NCE), in silico dissolution–absorption modeling can be effectively used to guide: API selection (form comparison and particle size properties), influence clinical study design, assess dosage form performance, guide strategy for dosage form design, and breakdown clinically relevant conditions on dosage form performance (pH effect for patients on pH-elevating treatments, and food effect). In the life-cycle management (LCM) stage of drug development, in vivo modeling is even more important in assessing the product performance for MR, DDI in a combination product and alternative delivery systems including parental depot, transdermal patch, and so on. For this session, papers on the application of in vivo modeling in guiding/assessing the development of drug product across all stages from Pre-POC to Phase 3 and LCM are encouraged.