Drug dissolution and transit in a heterogenous gastric chyme after fed administration: Semi-mechanistic modeling and simulations for an immediate-release and orodispersible tablets containing a poorly soluble drug

• DOI: 10.1016/j.ejpb.2024.114341
• Publication Date: 2024-05-23T22:12:07Z
• Authors: Dorota Danielak; Maciej Gajda; Tomasz Bołtromiuk; Katarzyna Sulikowska; Bartłomiej Kubiak; Michał Romański
• Keywords: Male; Adult; Cross-Over Studies; Viscosity; Stomach; Administration, Oral; Hydrogen-Ion Concentration; Models, Biological; Gastrointestinal Contents; Drug Liberation; Young Adult; Solubility; Therapeutic Equivalency; Gastric Emptying; Gastric Mucosa; Humans; Computer Simulation; Gastrointestinal Transit; Tablets

Mathematical models that treat the fed stomach content as a uniform entity emptied with constant rate may not suffice to explain pharmacokinetic profiles recorded in clinical trials. In reality, phenomena such Magenstrasse or chyme areas of different pH and viscosity, play an important role intragastric drug dissolution its transfer intestine. this study, we investigated data gathered bioequivalence trial between immediate-release tablet (Reference) orally dispersible (Test) poorly soluble weak base administered without water after high-fat high-calorie breakfast. Maximum concentrations (C