Fasted and fed state human duodenal fluids: Characterization, drug solubility, and comparison to simulated fluids and with human bioavailability

Accurate in vivo predictions of intestinal absorption low solubility drugs require knowing their physiologically relevant dissolution media. Aspirated human fluids (HIF) are the gold standard, followed by simulated HIF fasted and fed state (FaSSIF/FeSSIF). However, current characterization data vary, there is also some controversy regarding accuracy FaSSIF FeSSIF for predicting drug HIF. This study aimed at characterizing duodenal from 16 volunteers with respect to pH, buffer capacity, osmolarity, surface tension, as well protein, phospholipid, bile salt content. The samples were further used investigate equilibrium 17 representative low-solubility small-molecule drugs, six which confidential industry compounds 11 known characterized chemical diversity. These values then compared reported HIF, FeSSIF, bioavailability both states. compositions corresponded previously compositions. (both states) line FeSSIF. indicates that conditions proximal small intestine represented composition solubility. increased vs. states did not correlate changes same following oral administration either state.