Characterization of Human Intestinal Fluids after the Administration of a Solid Meal

Most available data on the composition and solubilizing properties of postprandial human intestinal fluid (HIF) are derived from studies involving liquid meals. These data inform the development of simulated intestinal fluids, widely used in in vitro assays for predicting intestinal drug behavior. However, the typical human diet primarily consists of solid meals, and the physical form of food has been shown to influence gastrointestinal transit and digestion, thereby affecting drug disposition and bioavailability. This study compares the characteristics of fed-state HIF collected after solid meal ingestion (SM-HIF) with previously published data on pooled liquid meal-derived HIF (LM-HIF) and newly generated data from individual LM-HIF samples. Time-dependent samples were analyzed over 180- and 90 min postprandial sampling periods to assess compositional changes following the administration of a solid and liquid meal, respectively. In addition, pooled samples were used to evaluate the solubilizing capacity for seven lipophilic model compounds. After intake of the solid meal, duodenal concentrations of exogenous (lipids, cholesterol, proteins) and endogenous (bile salts, phospholipids) components gradually increased to peak levels reached after 45-75 min. After 180 min, lipid and protein concentrations were still elevated compared to fasted state levels. In comparison to the liquid meal, the ingestion of the solid meal resulted in reduced concentrations of exogenous components, while endogenous components (bile salts and phospholipids) were relatively similar. For most compounds, the reduction in lipid content led to diminished solubilizing capacity of SM-HIF compared to LM-HIF when considering the combined micellar and lipid fractions. In contrast, the solubilizing capacity of the micellar fraction as such was largely independent of the meal type. Both the composition (particularly the micellar lipid concentration) and the solubilizing capacity of SM-HIF were highly variable between pools, albeit to a lesser extent than in LM-HIF. The findings of this study highlight that the physical form of the meal influences the composition and solubilizing capacity of HIF. These insights should be taken into account when refining biorelevant media for in vitro models to better predict food effects during drug product development.