More Than a Gut Feeling─A Combination of Physiologically Driven Dissolution and Pharmacokinetic Modeling as a Tool for Understanding Human Gastric Motility.

Autor:	Romański M; Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, 3 Rokietnicka St., 60-806 Poznań, Poland., Staniszewska M; Physiolution Polska, 74 Piłsudskiego St., 50-020 Wrocław, Poland., Dobosz J; Physiolution Polska, 74 Piłsudskiego St., 50-020 Wrocław, Poland., Myslitska D; Physiolution Polska, 74 Piłsudskiego St., 50-020 Wrocław, Poland., Paszkowska J; Physiolution Polska, 74 Piłsudskiego St., 50-020 Wrocław, Poland., Kołodziej B; Physiolution Polska, 74 Piłsudskiego St., 50-020 Wrocław, Poland., Romanova S; Physiolution Polska, 74 Piłsudskiego St., 50-020 Wrocław, Poland., Banach G; Physiolution Polska, 74 Piłsudskiego St., 50-020 Wrocław, Poland., Garbacz G; Physiolution Polska, 74 Piłsudskiego St., 50-020 Wrocław, Poland., Sarcevica I; Worldwide Research and Development, Pfizer R&D UK Ltd., Sandwich, CT13 9NJ, U.K., Huh Y; Worldwide Research and Development, Pfizer Inc., Groton, Connecticut 06340, United States., Purohit V; Worldwide Research and Development, Pfizer Inc., Groton, Connecticut 06340, United States., McAllister M; Worldwide Research and Development, Pfizer R&D UK Ltd., Sandwich, CT13 9NJ, U.K., Wong SM; Worldwide Research and Development, Pfizer R&D UK Ltd., Sandwich, CT13 9NJ, U.K., Danielak D; Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, 3 Rokietnicka St., 60-806 Poznań, Poland.
Jazyk:	angličtina
Zdroj:	Molecular pharmaceutics [Mol Pharm] 2024 Aug 05; Vol. 21 (8), pp. 3824-3837. Date of Electronic Publication: 2024 Jul 03.
DOI:	10.1021/acs.molpharmaceut.4c00117
Abstrakt:	In vivo studies of formulation performance with in vitro and/or in silico simulations are often limited by significant gaps in our knowledge of the interaction between administered dosage forms and the human gastrointestinal tract. This work presents a novel approach for the investigation of gastric motility influence on dosage form performance, by combining biopredictive dissolution tests in an innovative PhysioCell apparatus with mechanistic physiology-based pharmacokinetic modeling. The methodology was based on the pharmacokinetic data from a large ( n = 118) cohort of healthy volunteers who ingested a capsule containing a highly soluble and rapidly absorbed drug under fasted conditions. The developed dissolution tests included biorelevant media, varied fluid flows, and mechanical stress events of physiological timing and intensity. The dissolution results were used as inputs for pharmacokinetic modeling that led to the deduction of five patterns of gastric motility and their prevalence in the studied population. As these patterns significantly influenced the observed pharmacokinetic profiles, the proposed methodology is potentially useful to other in vitro - in vivo predictions involving immediate-release oral dosage forms.
Databáze:	MEDLINE
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