The ability of two in vitro lipolysis models reflecting the human and rat gastro-intestinal conditions to predict the in vivo performance of SNEDDS dosing regimens.

In this work, the influence of drug load and physical state of R3040 in self-nanoemulsifying drug delivery systems (SNEDDS) on R3040 absorption in rats was assessed. Furthermore, an in vitro lipolysis model simulating rat conditions (rat lipolysis model) was compared to a human lipolysis model in regard to the prediction of the in vivo data. The formulations were SNEDDS 80%, containing R3040 at 80% of its equilibrium solubility in SNEDDS (Seq); super-SNEDDS solution with R3040 supersaturated at 200% Seq; super-SNEDDS suspension containing R3040 at 200% Seq; Chasing principle (drug-free SNEDDS followed by R3040 aqueous suspension) and R3040 aqueous suspension. The pharmacokinetic profiles of R3040 in SNEDDS 80% and super-SNEDDS solution 200% were superimposed and higher than for super-SNEDDS suspension 200%, Chasing principle and aqueous suspension. Therefore, dosing R3040 dissolved in SNEDDS increased R3040 absorption irrespective of the drug load. While the human lipolysis model could not predict the rank order of absorption of the formulations, the rat lipolysis model predicted the similar absorption of R3040 in SNEDDS 80% and super-SNEDDS solution 200%. Thus, the rat lipolysis model showed to be an important step towards predictive in vitro models for rat studies.