目的 采用星点设计-效应面法优化阿维拉霉素自微乳化给药系统(SMEDDS),并进行质量评定。 方法 测定阿维拉霉素在各辅料中的溶解度,通过三相配伍实验筛选自微乳化基质;以微乳粒径、Zeta电位和分散系数(PDI)作为效应值,应用Design Expert 进行处方优化,并对阿维拉霉素自微乳制剂进行稳定性、释放度及抑菌活性考察。 结果 通过星点效应面优化获得阿维拉霉素自微乳的处方:丙二醇月桂酸酯(36.67%)、聚氧乙烯氢化蓖麻油(42.83%)、二乙二醇乙醚(20.50%),载药量为2%。将自微乳浓缩液加水乳化后粒径为(28.34±0.06) nm,Zeta电位为(-1.98±0.24) mV,PDI为(0.15±0.005),并具有较好的体外抑菌活性。结论 成功制备了阿维拉霉素SMEDDS,质量稳定,可显著改善阿维拉霉素的溶出度,有望提高阿维拉霉素动物体内口服生物利用度。
Abstract
OBJECTIVE To optimize the formulation of avilamycin self-microemulsifying drug delivery system (SMEDDS)using central composite design-response surface method and evaluate its quality. METHODS The compositions of avilamycin SMEDDS were screened by solubility experiment and self-emulsifying grading test. The formulation was optimized using Design Expert Software, taking particle size and Zeta potential as dependent variables and the usage amounts of oil, surfactant and cosurfactant as independent variables. RESULTS The optimized formulation was quickly and conveniently obtained as follows:36.67% propylene glycollaurate, 42.83% cremophor RH40 and 20.50% diethylene glycol monoethyl ether.The average diameter of the preparation was (28.34±0.06)nm, the Zeta potential was (-1.98±0.24)mV and PDI was (0.15±0.005). CONCLUSION The central composite design and response surface method is useful for the formula optimization of avilamycin self-microemulsifying drug delivery system.The prediction accuracy of the established mode1 is good.
关键词
阿维拉霉素 /
自微乳化 /
伪三元相图 /
星点设计 /
质量评价
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Key words
avilamycin /
self-microemulsification /
pseudo ternary phase diagram /
central composite design-response /
quality evaluation
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中图分类号：
R944
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参考文献
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脚注
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基金
浙江省新苗人才计划资助项目(2014R408085)
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