非诺贝特纳米悬液的制备及在Beagle犬体内的生物利用度

Preparation and Bioavailability of Fenofi brate Nanosuspension in Beagle Dogs

采用沉淀法结合高压均质法制备非诺贝特纳米混悬液,利用单因素试验所得优化处方为:选择羟丙甲纤维素E3120 mg和十二烷基硫酸钠30 mg的组合为稳定剂,无水乙醇1 ml为有机溶剂,最高均质压力1 000 bar。所得制品粒径为(439.1±30)nm,多分散指数(PDI)为(0.226±0.015),?电位为(-28.3±0.8)mV。以市售胶囊(Lipanthyl)为参比制剂,考察纳米混悬液的体外溶出与Beagle犬的口服生物利用度。结果表明,制品在2和5 min时溶出度为76%和98%,溶出明显快于参比制剂(5和60 min时溶出度为8%和83%)。Beagle犬口服非诺贝特纳米混悬液后,t max显著缩短,c max和AUC0→t分别是Lipanthyl的8倍和6倍,相对生物利用度为598%。

The fenofibrate nanosuspension was prepared by precipitation combined with high-pressure homogenization method. The optimal formulation was obtained by single factor method. The particle size, polydispersion index （PDI） and ξ potential of the optimal nanosuspension prepared with HPMC E3 120 mg and sodium dodecylsulfate （SDS） 30 mg as stabilizers, ethanol 1 ml as the organic solvent and the highest homogenization pressure of 1 000 bar were （439.1±30）nm, （0.226±0.015） and （-28.3±0.8）mV, respectively. The in vitro dissolution and oral bioavailability in Beagle dogs were investigated with the marketed capsule Lipanthyl~ as the reference preparation. The results showed that the release rate of fenofibrate from the nanosuspension was significantly higher than Lipanthyl. The cumulative dissolution at 2 and 5 rain were 76% and 98% for nanosuspension, while only 8% and 83% for Lipanthyl at 5 and 60 min. After oral administration of fenofibrate nanosuspension, the tmax of fenofibric acid was significantly reduced while the Cmax and AUC0-t, were increased by 8- and 6-fold, respectively, compared with Lipanthyl. The relative oral bioavailability of the nanosuspension was 598 %.