湿法研磨制备塞来昔布纳米混悬剂及体外溶出性考察

Preparation of Celecoxib Nanosuspension by Wet Milling and in Vitro Dissolution Study

目的制备塞来昔布纳米混悬剂,促进药物溶出。方法采用湿法研磨技术,选定十二烷基硫酸钠(SDS)与聚乙烯吡咯烷酮(PVP)K30用量比例,药物浓度,研磨时间为考察因素,通过正交设计进行试验,以药物粒径(D90)为指标,优化湿法研磨制备塞来昔布纳米混悬剂的处方工艺,并进行验证,同时与原料药及模拟剂对比溶出度。结果最佳制备工艺为SDS与PVP K30联用比例为1∶1,药物浓度为10%,研磨时间为4h。按此优化后工艺所得粒径可稳定14天,且纳米混悬剂的溶出效果明显优于原料药。结论难溶药物塞来昔布制成纳米混悬剂后可以显著改善其溶出度。

OBJECTIVE To Prepared Celecoxib nanosuspension so as to improve the dissolution.METHODS Celecoxib nanosuspension was prepared by wet milling technology.The preparation technology was optimized by orthogonal test with ratio of the amount of sodium lauryl sulfate(SDS)to polyvinylpyrrolidone(PVP)K30,the concentration of celecoxib and milling time as factors and with particle size(D90)as index.The optimized technology was verified.The dissolution rate were investigated to compare suspension with active pharmaceutical ingredients and simulation agent.RESULTS The optimized technology was as follows:the ration of amount of SDS to PVP K30 was 1∶1,the concentration of celecoxib was 10%,milling time was 4 hours.According to this optimized process,the particle size can be stable for 14 days.The dissolution of nanoparticle suspension agent is superior to active pharmaceutical ingredients.CONCLUSION Celecoxib nanosuspension can effective increase solubility.