Fenofibrate oral absorption from SNEDDS and super-SNEDDS is not significantly affected by lipase inhibition in rats

The effect of drug load and digestion on the solubilization and absorption of fenofibrate in self-nanoemulsifying drug delivery system (SNEDDS) was assessed in a pharmacokinetic study in rats and in an in vitro lipolysis model. SNEDDS containing fenofibrate at 75% of equilibrium solubility (S-eq), a super-saturated SNEDDS (super-SNEDDS) containing fenofibrate at 150% of S-eq and a super-SNEDDS suspension containing fenofibrate at 100% of S-eq and an additional 50% S-eq fenofibrate suspended (150% of S-eq in total) were used. To assess the effect of lipid digestion on fenofibrate absorption in rats and fenofibrate solubilization during in vitro lipolysis, the lipase inhibitor orlistat was added at 1% (w/w) to the SNEDDS, resulting in six different SNEDDS: SNEDDS, super-SNEDDS and super-SNEDDS suspension with and without orlistat 1% (w/w). In vivo, super-SNEDDS had a higher C-max and AUC(0-30h) compared to SNEDDS and super-SNEDDS suspension, both with and without orlistat. While orlistat did not affect fenofibrate absorption in SNEDDS and super-SNEDDS, an increase of T-max and AUC(0-30h) for super-SNEDDS suspension was found when orlistat was present. During in vitro lipolysis, the addition of orlistat decreased digestion and lowered drug precipitation. Super-SNEDDS showed significantly increased absorption in rats compared to SNEDDS and super-SNEDDS suspension and the inhibition of digestion resulted in prolonged and increased absorption for the super-SNEDDS suspension.