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 (Seq), a super-saturated SNEDDS (super-SNEDDS) containing fenofibrate at 150% of Seq and a super-SNEDDS suspension containing fenofibrate at 100% of Seq and an additional 50% Seq fenofibrate suspended (150% of Seq 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 Cmax and AUC0-30h 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 Tmax and AUC0-30h 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.

Michaelsen MH ，Siqueira Jørgensen SD ，Abdi IM ，Wasan KM ，Rades T ，Müllertz A ... -  《-》

The Effect of Digestion and Drug Load on Halofantrine Absorption from Self-nanoemulsifying Drug Delivery System (SNEDDS).

Michaelsen MH ，Wasan KM ，Sivak O ，Müllertz A ，Rades T ... -  《AAPS Journal》

Influence of drug load and physical form of cinnarizine in new SNEDDS dosing regimens: in vivo and in vitro evaluations.

Siqueira SD ，Müllertz A ，Gräeser K ，Kasten G ，Mu H ，Rades T ... -  《AAPS Journal》

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.

Siqueira Jørgensen SD ，Al Sawaf M ，Graeser K ，Mu H ，Müllertz A ，Rades T ... -  《-》

Development of self-nanoemulsifying drug delivery systems for the enhancement of solubility and oral bioavailability of fenofibrate, a poorly water-soluble drug.

Mohsin K ，Alamri R ，Ahmad A ，Raish M ，Alanazi FK ，Hussain MD ... -  《-》