Characterisation of fenofibrate dissolution delivered by a self-microemulsifying drug-delivery system

Objectives This study attempted to characterise the in‐vitro release profiles of fenofibrate (FFB) from a self‐microemulsifying drug‐delivery system (SMEDDS) for optimising formulation factors and dissolution conditions for in‐vivo absorption. Methods The study was conducted by profiling the release of FFB formulated with either a complete solution or a micronised dispersion system (MDS) in a SMEDDS composed of medium‐chain triglyceride (MCT) oil and surfactant mixtures (Smix) of TPGS and Tweens at different ratios (Km = TPGS/Tweens), with and without adding water. Optimised FFB SMEDDS formulations were then selected for in‐vivo bioavailability study. Key findings The release rates of FFB from TPGS/Tween 20 systems were faster than those from TPGS/Tween 80 systems at the same Km value. In both systems, the release rates of FFB increased with a decrease in the Km value. Furthermore, both the release rates and the amounts of FFB from MDS in the water medium decreased with an increasing percentage of Smix added to both water contents. However, the release rates and amounts of FFB from MDSs increased with an increasing percentage of Smix in a 0.025 M sodium lauryl sulfate (SLS) solution. It was further illustrated that the release of FFB from SMEDDSs was complete within 30 min in both the 0.025 M SLS solution and water medium, but the release of FFB from Tricor® or MDSs was limited in water medium. An optimised FFB SMEDDS with either Tween 20(E5(20)) or Tween 80(E5(80)) and one MDS were selected for a pharmacokinetic study to compare with Tricor®. The results demonstrated that the area under the receiver operating curve and Cmax values were in the order of Tricor® > E5(80) ≅ E5(20) > MDS and Tricor® ≅ E5(80) > E5(20) > MDS, respectively. Conclusions The absorption of drug carried by SMEDDS might not be enhanced as a result of the smaller volume of water taken with oral administration of SMEDDSs and the agitation rate of the gastrointestinal tract not being strong enough to efficiently promote the self‐microemulsification process to facilitate the in‐vivo dissolution rate.