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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 investigate the effects of supersaturated substances on the release characteristics of docetaxel self-emulsifying system (DTX-SEDDS). Methods The in vitro dissolution of DTX-SEDDS was assayed and the effects of different supersaturated substances, different dosage of supersaturated substances, different doses and different release media on in vitro release characteristics of DTX-SEDDS were investigated. Results HPMC, HPMC, SDS, PVPK30 and Avicel RC591 had the strongest role in promoting solubilization and stabilization. Different manufacturers with the same viscosity of HPMC drug dissolution effect was not significant difference with the same concentration of different viscosity HPMC drug dissolution significantly different, low viscosity better than high viscosity HPMC; HPMC different dosage of DTX-SEDDS in vitro release When the dosage of low viscosity HPMC was 1% ~ 8%, the cumulative dissolution percentage had no significant difference. When the content of high viscosity HPMC was less than 0.5% or ≥8%, the dissolution of drug obviously decreased; the effect of different media on drug dissolution was insignificant Sex differences. Recommended self-emulsifying prescription choose to join 1% to 8% of low viscosity HPMC (Model: Shandong 50, Shandong 100 or Shanghai K100) better. Conclusion The supersaturated substance HPMC can significantly improve the dissolution and stability of DTX-SEDDS, meanwhile reduce the amount of self-emulsifying oil and improve the clinical safety of self-emulsifying preparation.