(584ai) Computational Model to Predict the Effect of Lipids On Pharmacokinetic Profiles in Vivo

Dosing lipids, either as a formulation or concurrently with food, has been shown to improve drug bioavailability and absorption for many orally dosed poorly water soluble drugs. While numerous studies have shown this to be the case, there are relatively few commercial lipid-based drug delivery systems, and the effect of food is often not exploited to improve bioavailability, in part because these effects are not currently amenable to quantitative prediction. A computational model based on multiple dynamic processes, such as lipid digestion and drug dissolution kinetics, has been proposed to predict the pharmacokinetic profiles of drugs when dosed either in formulation with lipids or with food. The model was built from in vitro experiments that simulate digestion and absorption in the small intestinal environment. In an in vivo validation study, blood plasma concentrations of the drug were compared to predicted values from the model. Both drug formulated with lipids as a self-emulsifying drug delivery system (SEDDS) and drug co-dosed with soy bean oil were studied. Results show the feasibility of this model to predict the effect of lipids dosed with drug to increase bioavailability, and thus provide rational guidance for design of lipid-based drug delivery systems.