伊立替康微乳的制备及体外释药评价

Preparation and in vitro release evaluation of irinotecan microemulsion

摘要

采用伪三元相图法筛选伊立替康空白微乳的处方组分,以平均粒径、多分散性指数(polydispersity index, PDI)和载药量为评价指标 ,确定最佳处方并成功制备伊立替康载药微乳.对该微乳的制剂学特性和体外释药行为进行考察,结果发现:以油酸聚乙二醇甘油酯1944-CS为油相、RH60为乳化剂、PEG300为助乳化剂且乳化剂和助乳化剂的质量比(Km)为3∶1时,所得微乳区域面积最大、性状最为稳定;当伊立替康的载药量为体系总质量的0.5%时,制得的微乳呈圆球状,分散均匀,平均粒径为(78.12±2.42)nm、PDI为0.342±0.031、电动电位(Zeta电位)为(-1.93±0.51)mV,且具有良好的离心稳定性和时间稳定性,24h累积药物释放率显著低于游离药物.可见,所制备的伊立替康微乳具备良好的稳定性和药物缓释性能,有望为伊立替康的临床抗肿瘤治疗提供可行的药物剂型解决方案.

Abstract

The formulation components of irinotecan blank microemulsion were screened using the pseudo-ternary phase diagram method. The optimal formulation was determined based on evaluation indices including mean particle size , polydispersity index (PDI ), and drug loading capacity , and the irinotecan-loaded microemulsion was successfully prepared. The pharmaceutical characteristics and in vitro drug release behavior of the microemulsion were investigated. The results showed that when 1944-CS was used as the oil phase , RH60 as the emulsifier , PEG300 as the co-emulsifier , and the mass ratio (Km ) of the emulsifier to the co-emulsifier was 3∶1 , the obtained microemulsion exhibited the largest area and the most stable properties. When the drug loading of irinotecan was 0.5% of the total system mass , the prepared microemulsion appeared spherical with uniform dispersion , a mean particle size of (78.12±2.42 ) nm , a PDI of 0.342±0.031 , a Zeta potential of (-1.93±0.51 ) mV , and demonstrated good centrifugal stability and temporal stability. The 24-hour cumulative drug release rate was significantly lower than that of the free drug. Thus , the prepared irinotecan microemulsion possesses good stability and sustained-release properties , suggesting its potential as a feasible pharmaceutical formulation for the clinical anti-tumor therapy of irinotecan.

关键词

伊立替康 / 微乳 / 伪三元相图

Key words

irinotecan / microemulsion / pseudo-ternary phase diagram

参考文献

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基金资助

安徽省自然科学基金项目(2108085QH370)

国家科学中心大健康研究院新安医学与中医药现代化研究所“揭榜挂帅”项目(2023CXMMTCM023)

安徽省大学生创新创业训练项目(S202010368065)

安徽省分子基材料省级实验室开放基金项目(fzj22016)