Fenofibrate Solid Self-emulsifying Formulation

OBJECTIVE: Drugs always have low bioavailability in vivo because of their insolubility in water. Self-emulsify drug delivery system (SEDDS) has great successful in increasing their oral absorption, but high content of surfactants in liquid SEDDS (L-SEDDS) can cause side effects on gastrointestine tract. The solid self-emulsified drug delivery system(S-SEDDS) of highly lipophilic drug fenofibrate was studied which contained appropriate solid excipient instead of liquid surfactants and also emulsified when dispersed into water. S-SEDDS can enhance the dissolution rate in vitro and bioavailability in vivo of fenofibrate and avoid side effects that caused by surfactant. METHODS: Combined the characteristics of emulsion and solid granules, particle size distribution, dissolution rate in vitro and flowability were investigated to select the formulation. X-ray, the differential scanning calorimetry thermogram analysis(DSC), scanning electron micrographs (SEM) and light microscope have been used to observe the appearance and state of S-SEDDS. The pharmacokinetic parameters and bioavailability of S-SEDDS in beagle dogs were also studied compared with the market capsule and the liquid SEDDS formulation. The stability of S-SEDDS was also investigated. RESULTS: The average size of S-SEDDS after dispersion is 820.2±26.5 (nm). Dissolution test showed that the accumulated dissolution of S-SEDDS was over 80% in water within 45 min. The X-ray powder diffraction of pure fenofibrate has sharp peak at angle of 2θin the range of 10-40°. But S-SEDDS and the empty excipients have several obtuse peak in the range of 15-25°. In DSC test, endothermic peak of pure fenofibrate appeared at temperature of 78.55-83.55℃, but not exist in S-SEDDS. The results of X-ray and DSC test suggested that the drug was amorphous in S-SEDDS. The pictures of scanning electron microscopy showed the appearance of S-SEDDS was porous, granule. In vivo study, AUC (0-24) was 22.7±8.2 mg·L^-1·h in S-SEDDS and 24.9±7.6 mg·L^-1·h in L-SEDDS, respectively.There is no significant difference between S-SEDDS and L-SEDDS and the both formulations improved the bioavailability in vivo remarkably compared with the market capsule ( 13.8±10.5 mg·L^-1·h ) . CONCLUSION: The solid self-emulsified drug delivery system(S-SEDDS) of fenofibrate was prepared and can emulsify when dispersed into water.It can enhance the dissolution rate in vitro and bioavailability in vivo free of surfactant and had better stability during storage and manufacture.