Improving Dissolution Behavior and Oral Absorption of Drugs with pH-Dependent Solubility Using pH Modifiers: A Physiologically Realistic Mass Transport Analysis

• Published in: Molecular pharmaceutics Vol. 18; no. 9; pp. 3326 - 3341
• Main Authors: Salehi, Niloufar, Kuminek, Gislaine, Al-Gousous, Jozef, Sperry, David C, Greenwood, Dale E, Waltz, Nicholas M, Amidon, Gordon L, Ziff, Robert M, Amidon, Gregory E
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 06.09.2021
• Subjects: Administration, Oral; Betaine - pharmacology; Biological Availability; Chemistry, Pharmaceutical; Computer Simulation; Drug Design; Drug Liberation; Excipients - pharmacology; Fumarates - pharmacology; Gastrointestinal Absorption - drug effects; Humans; Hydrogen-Ion Concentration - drug effects; Models, Biological; Solubility; Tartrates - pharmacology; mass transport model; surface solubility; hierarchical mass transfer model; surface pH; dissolution modeling; pH modifier; proton pump inhibitor; achlorhydria; diffusion layer model; H2 blockers; gastrointestinal simulator; physiological mass transfer model; elevated gastric pH; H2 antagonists

Orally dosed drugs must dissolve in the gastrointestinal (GI) tract before being absorbed through the epithelial cell membrane. In vivo drug dissolution depends on the GI tract’s physiological conditions such as pH, residence time, luminal buffers, intestinal motility, and transit and drug propertie...