Efficient delivery of oral drugs is dependent on their solubility in human intestinal fluid, a complex and dynamic fluid that contains colloidal structures composed of small molecules. These structures solubilize poorly water-soluble compounds, increasing their apparent solubility, and possibly their bioavailability. In this study, we conducted coarse-grained molecular dynamics simulations with data from duodenal fluid samples previously acquired from five healthy volunteers. In these simulations, we observed the self-assembly of mixed micelles of bile salts, phospholipids, and free fatty acids. The micelles were ellipsoids with a size range of 4-7 nm. Next, we investigated micelle affinities of three model drugs. The affinities in our simulation showed the same trend as literature values for the solubility enhancement of drugs in human intestinal fluids. This type of simulations is useful for studies of events and interactions taking place in the small intestinal fluid.
Keywords: MD simulations; coarse-grained simulations; drug solubility; intestinal fluids; micelles.