非诺贝特纳米混悬剂的制备及在大鼠体内的药动学研究  

Formulation, optimization and in vivo pharmacokinetics of fenofibrate nanosuspension

作　　者：祁万朋 韩雪梅[1] 董文向 王永军[1] 孙进[1] QI Wan-peng HAN Xue-mei DONG Wen-xiang WANG Yong-jun SUN Jin(School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016)

机构地区：[1]沈阳药科大学药学院,沈阳110016

出　　处：《中南药学》2016年第11期1210-1215,共6页Central South Pharmacy

基　　金：国家自然科学基金项目(编号:81173008)

摘　　要：目的制备非诺贝特纳米混悬剂并对其体外释放行为及体内药动学进行研究。方法通过泡腾法制备非诺贝特纳米混悬剂,以单因素实验来筛选处方,并通过粒径分布、透射电镜和差示扫描量热法进行表征。以市售微粉化胶囊为参比制剂,考察自制纳米混悬剂在0.5%SDS介质中的释放行为,同时采用UPLC-MS/MS法对其在大鼠体内的药动学进行研究。结果优化处方为非诺贝特2 mg,泊洛沙姆407（F127）3 mg,柠檬酸6 mg,碳酸氢钠7.87 mg。与参比制剂相比,自制处方粉末在0.5%SDS的介质中溶出度不如市售制剂好;药动学研究结果表明,自制纳米混悬剂与参比制剂的tmax、Cmax及AUC0-t均存在显著性差异,相对生物利用度为145.2%。结论泡腾法制备非诺贝特纳米混悬剂方法可行,体内生物利用度较高。Objective To prepare fenofibrate nanosuspension and evaluate the in vitro release and in vivo pharmacokinetics of the formulation. Methods Effervescent method was used to prepare fenofibrate nanosuspension and the optimized formulation was obtained by single-factor experiment. The preparation was characterized by PXRD, TEM and DSC analysis. The dissolution behaviors of the tested powder were evaluated in 0.5%SDS to compare with the commercial capsules. The in vivo pharmacokinetics of the nanosuspension was studied in rats with UPLC-MS/MS method. Results The optimized formulation included 2 mg fenofibrate, 3 mg P407（F127）, 6 mg citric acid and 7.87 mg Na HCO3. The dissolution degree of the reference was not better than the tested powder in 0.5%SDS. In addition, the pharmacokinetic study illustrated significant difference in the parameters of tmax, Cmax and AUC0-t between the tested nanosuspension and the reference. The relative bioavailability was 145.2%. Conclusion The effervescent method is well employed in the preparation of fenofibrate nanosuspension and it proves better in vivo absorption in rats compared with the reference.

关 键 词：非诺贝特 纳米混悬剂 泡腾法 药动学 

分 类 号：R94[医药卫生—药剂学]