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

Area of Science:

• Gastroenterology and Drug Delivery
• Physicochemical properties of intestinal fluids

Background:

• Existing data on human intestinal fluid (HIF) composition and drug solubilization primarily use liquid meals, informing simulated intestinal fluid development.
• The physical form of food (solid vs. liquid) significantly impacts gastrointestinal processing, drug disposition, and bioavailability.

Purpose of the Study:

• To compare the composition and solubilizing capacity of HIF after solid meal ingestion (SM-HIF) with liquid meal-derived HIF (LM-HIF).
• To assess the impact of meal physical form on biorelevant media development for drug product development.

Main Methods:

• Collected time-dependent fed-state HIF samples after solid and liquid meal ingestion.
• Analyzed duodenal fluid composition (lipids, bile salts, proteins, phospholipids) over 180 min (solid) and 90 min (liquid).
• Evaluated the solubilizing capacity of pooled SM-HIF and LM-HIF for seven lipophilic compounds.

Main Results:

• Solid meal ingestion led to a gradual increase in exogenous and endogenous components, with elevated lipid and protein levels persisting for 180 min.
• SM-HIF showed reduced exogenous components but similar endogenous components compared to LM-HIF.
• Overall solubilizing capacity was diminished in SM-HIF due to lower lipid content, while micellar fraction capacity remained similar.
• SM-HIF composition and solubilizing capacity exhibited high inter-individual variability.

Conclusions:

• The physical form of the meal significantly influences the composition and solubilizing capacity of postprandial human intestinal fluid.
• Current biorelevant media may not adequately represent SM-HIF, necessitating refinement for accurate prediction of food effects in drug development.
• Meal-type specific biorelevant media are crucial for improving in vitro models to better predict in vivo drug behavior.