非洛贝特纳米混悬剂的制备及其体外溶出性考察

Preparation of Fenofibrate Nanosuspension and in Vitro Dissolution Study

目的:制备非洛贝特纳米混悬剂,以促进药物溶出。方法:以非洛贝特为主药,采用熔融乳化法联合高压均质法制备纳米混悬剂;选取处方中表面活性剂泊洛沙姆188(Poloxamer188)与聚乙烯吡咯烷酮(PVP)K30用量比、均质压力、均质次数为考察因素,药物粒径为指标设计正交试验筛选制备工艺,并进行验证试验;同时考察制剂溶出速率和溶出浓度。结果:最佳制备工艺为Poloxamer188:PVPK30用量比2:1、均质压力800bar,均质次数为9。所制纳米粒平均粒径为356nm,多分散系数为0.19,平均Zeta电位为-39mV。制剂5min时溶出浓度可达20.10mg·L-1,4h时达25.46mg·L-1,接近完全溶出。结论:将难溶药物非诺贝特制成纳米混悬剂可以显著改善其溶出作用。

OBJECTIVE： To prepare Fenofibrate nanosuspension so as to improve the dissolution of it. METHODS： Fenofibrate nanosuspension was prepared by melting-emulsifcation method combined with high pressure homogenization using fenofibrate as main component. The preparation technology was optimized by orthogonal test with ratio of the amount of Poloxamer 188 to that of PVP K30, homogenization pressure and homogenization time as factors and with particle size as index. The optimized technology was verified. The dissolution rate and dissolved concentration of preparation were investigated. RESULTS： The optimized technology was as follows： the ratio of amount of Poloxamer 188 to PVP K30 was 2： 1; homogenization pressure of 800 bar and homogenization time of 9 times. Mean particle size of prepared nanoparticle was 356 nm and polydispersity index was 0.19 with average Zeta potential of --39 mV. The dissolved concentration of preparation was 20.10 mg·L^-1 at 5 min and 25.46 mg·L^-1 at 4 h. Prepared nanoparticle had nearly dissolved completely. CONCLUSION： Fenofibrate nanosuspension can effectively increase solubility of fenofibrate.