Design of fenofibrate microemulsion for improved bioavailability

• Published in: International journal of pharmaceutics 2011-11, Vol.420 (2), p.251-255
• Main Authors: Hu, Liandong, Wu, Hongyu, Niu, Feng, Yan, Cuihong, Yang, Xun, Jia, Yanhong
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; bioavailability; Biological Availability; Capsules; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Dogs; droplet size; Drug Compounding; Drug Stability; drugs; Emulsions; Ethylene Glycols - chemistry; Fenofibrate; Fenofibrate - blood; Fenofibrate - chemistry; Fenofibrate - pharmacokinetics; Glycerides - chemistry; Glycerol - analogs & derivatives; Glycerol - chemistry; Hypolipidemic Agents - blood; Hypolipidemic Agents - chemistry; Hypolipidemic Agents - pharmacokinetics; Male; Microemulsion; Microscopy, Electron, Transmission; oils; Oral; oral administration; Pharmacokinetics; physical phases; Polyethylene Glycols - chemistry; Solubility; Solubilization; Surface-Active Agents - chemistry; surfactants
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2011.08.043

The objective of the present study was to formulate a microemulsion system for oral administration to improve the solubility and bioavailability of fenofibrate. Various formulations were prepared using different ratios of oils, surfactants and co-surfactants (S&CoS). Pseudo-ternary phase diagrams were constructed to evaluate the microemulsification existence area. The formulations were characterized by solubility of the drug in the vehicles, mean droplet size, and drug content. The stability was also investigated by store for 3 months under 4 °C, 25 °C and 40 °C and diluted 100 times for 3 days. The optimal formulation consists of 25% Capryol 90, 27.75% Cremophore EL, 9.25% Transcutol P and 38% water (w/w), with a maximum solubility of fenofibrate up to ∼40.96 mg/mL. The microemulsion was physicochemical stable and mean droplet size was about 32.5–41.7 nm. The pharmacokinetic study was performed in dogs and compared with Lipanthy ® capsule. The result showed that microemulsion has significantly increased the C max and AUC compared to that of Lipanthy ® capsule ( p < 0.05). The oral bioavailability of fenofibrate microemulsions (FEN-MEs) in ME-3 and ME-4 were 1.63 and 1.30-fold higher than that of the capsule. Our results indicated that the microemulsions could be used as an effective formulation for enhancing the oral bioavailability of fenofibrate.