title: Physiologically Based Absorption Modeling to Impact Biopharmaceutics and Formulation Strategies in Drug Development-Industry Case Studies.
abstract: In recent years, there has been a significant increase in use of physiologically based pharmacokinetic models in drug development and regulatory applications. Although most of the published examples have focused on aspects such as first-in-human (FIH) dose predictions or drug-drug interactions, several publications have highlighted the application of these models in the biopharmaceutics field and their use to inform formulation development. In this report, we present 5 case studies of use of such models in this biopharmaceutics/formulation space across different pharmaceutical companies. The case studies cover different aspects of biopharmaceutics or formulation questions including (1) prediction of absorption prior to FIH studies; (2) optimization of formulation and dissolution method post-FIH data; (3) early exploration of a modified-release formulation; (4) addressing bridging questions for late-stage formulation changes; and (5) prediction of pharmacokinetics in the fed state for a Biopharmaceutics Classification System class I drug with fasted state data. The discussion of the case studies focuses on how such models can facilitate decisions and biopharmaceutic understanding of drug candidates and the opportunities for increased use and acceptance of such models in drug development and regulatory interactions.
authors.affiliation: Biopharmaceutics, Pharmaceutical Sciences and Clinical Supply, Merck & Co, Inc., West Point, Pennsylvania 19486. Electronic address: filippos_kesisoglou@merck.com.
authors.forename: Filippos
authors.initials: F
authors.lastname: Kesisoglou
authors.affiliation: Oral Delivery Product and Process Development, Amgen, Inc., Thousand Oaks, California 91320.
authors.forename: John
authors.initials: J
authors.lastname: Chung
authors.affiliation: Non-Clinical Development, New Medicines, UCB Pharma, B - 1420, Braine-L'Alleud, Belgium.
authors.forename: Judith
authors.initials: J
authors.lastname: van Asperen
authors.affiliation: Drug Metabolism and Pharmacokinetics, Novartis Institutes for Biomedical Research, East Hanover, New Jersey 07936.
authors.forename: Tycho
authors.initials: T
authors.lastname: Heimbach
mesh_terms: D000818:Animals; D001702:Biopharmaceutics; D003198:Computer Simulation; D004285:Dogs; D004339:Drug Compounding; D004345:Drug Industry; D006801:Humans; D007408:Intestinal Absorption; D008954:Models, Biological; D010316:Particle Size; D010599:Pharmacokinetics; D011237:Predictive Value of Tests; D012984:Software; D013810:Therapeutic Equivalency
keywords: absorption; food effects; oral absorption; particle size; pharmacokinetics; physiologically based pharmacokinetic modeling