促过饱和物质对多西他赛自乳化系统体外释药特性的影响  

Effect of Supersaturated Promoter on the Dissolution of Self-Emulsifying Drug Delivery System of Docetaxel

作　　者：陈鹰[1] 杜蓉[1] 曾晓枫[2] 史琼枝[1] 刘宏[1] 

机构地区：[1]广州军区武汉总医院药剂科,武汉430070 [2]湖北中医学院,武汉430065

出　　处：《中国药学杂志》2010年第6期444-449,共6页Chinese Pharmaceutical Journal

基　　金：湖北省科技攻关课题(2007AA301B15号);湖北省自然科学基金计划重点项目(2007ABA071)

摘　　要：目的研究促过饱和物质对多西他赛自乳化系统(DTX-SEDDS)释药特性的影响。方法测定DTX-SEDDS的体外溶出度,并考查不同的促过饱和物质,促过饱和物质的不同用量,不同的投药量以及不同的释放介质对DTX-SEDDS体外释药特性的影响。结果不同的促过饱和物质如羟丙基甲基纤维素(HPMC)、十二烷基磺酸钠(SDS)、聚维酮(PVPK30)、AvicelRC591中,HPMC的促溶和稳定作用最强;不同厂家同黏度的HPMC对药物溶出影响差异不显著,同浓度不同黏度的HPMC对药物溶出影响有显著性差异,低黏度的好于高黏度HPMC;HPMC的不同用量对DTX-SEDDS体外释药有一定影响;当低黏度HPMC的用量为1%～8%,累积溶出百分率无显著差异,当高黏度HPMC的用量≤0.5%或≥8%时药物溶出明显减少;不同介质对药物溶出影响无显著性差异。推荐自乳化处方中选择加入1%～8%的低黏度HPMC(型号:山东50,山东100或上海K100)效果较好。结论过饱和物质HPMC可以明显提高DTX-SEDDS的溶出和稳定性,同时可减少自乳化油的用量,可提高自乳化制剂的临床安全性。OBJECTIVE To study the effect of supersaturated promoter on the dissolution of self-microemulsifying drug delivery system of docetaxel（DTX-SEDDS）. METHODS In vitro Dissolution of DTX-SEDDS as determined with resource and quantity of supersaturated promoter, drug content given, and medias. RESULTS HPMC showed the strongest promotion effect on dissolution and stability among the turated promoters such as HPMC, PVPK30, SDS and Avicel RC591. There were not obvious differences on dissolution with different factory and similar viscosity of HPMC, but apparent differences existed in HPMC with the same concentration and different viscosity. HPMC with low viscosity was better than high viscosity. Different content of HPMC had some effect on the dissolution of DTX-SEDDS. In the range of 1% -8% , the effects of low viscosity HPMC on dissolution were not apparently different, but the dissolution decreased apparently using high viscosity HPMC ≤0. 5% or ≥8%. Different media had not apparent effects on the dissolution. Finally, the formulation of DTX-SEDDS with 1% -8% low viscosity HPMC such as Shandong 50, Shandong 100 and Shanghai K100 was recommended. CONCLUSION The dissolution and stability of DTX-SEDDS would be apparently improved by adding supersaturated promoter such as HPMC, and could reduce the quantity of surfzctant in formulation. It would promote the safety of SEDDS preparations for clinic use.

关 键 词：多西他赛 促过饱和物质 自乳化释药系统 溶出度 

分 类 号：R944[医药卫生—药剂学]