目的 采用伪三元相图联合星点设计效应面法(CCD-RSM)获得制备益康唑固体脂质纳米粒(E-SLN)的最佳处方。方法 首先筛选益康唑在不同固体脂质中的溶解度,并初步评价固体脂质的成乳能力,然后采用伪三元相图法获得形成微乳的区域,采用微乳法制备E-SLN,分别以药物/脂质(X1)、脂质/表面活性剂(X2),表面活性剂/助表面活性剂(X3)为考察对象,以包封率(Y1)、粒径(Y2)、Zeta电位(Y3)为考察指标,根据CCD-RSM计算获得E-SLN的最佳处方,并对最佳处方进行验证。结果 三棕榈酸甘油酯、单硬脂酸甘油酯、硬脂酸和月桂酸甘油酯对益康唑均有较好的溶解能力,但三棕榈酸甘油酯成乳能力较好,根据CCD-RSM获得的最佳处方为益康唑0.06 g、三棕榈酸甘油酯0.48 g、聚山梨酯80为1.194 g、甘油为0.274 g,加水至30 mL。以最佳处方制备的E-SLN包封率为(94.06±1.54)%,与预测值偏差为2.61%;粒径为(18.88±0.38)nm,与预测值偏差为0.34%;Zeta电位为(3.53±0.031)mV,偏差为3.62%。结论 采用伪三元相图联合CCD-RSM获得的E-SLN稳定且包封率高、粒径小,可用于后续研究。
Abstract
OBJECTIVE To optimize the formulation of econazole solid lipid nanoparticles(E-SLN) by combining pseudo-ternary phase diagrams and central composite design-response surface methodology (CCD-RSM). METHODS Econazole solubility in different solid lipids and the capacity of lipid emulsion were tested. The microemulsion region was obtained by the pseudo-ternary phase diagrams. Then the E-SLN were prepared by microemulsion method. Drug/lipid (X1), lipid/surfactant (X2) and surfactant/cosurfactant (X3) were taken as individual factors, the encapsulation efficiency (Y1), particle size (Y2), Zeta potential (Y3) were taken as the dependent factors. The possible optimum formulation was predicted by CCD-RSM and validated. RESULTS Econazole could be dissolved in tripalmitic acid glyceride (TAG), monostearic acid glyceride, stearic acid and lauric acid glyceride. TAG had a good capacity of emulsion. The optimized formulation was econazole 0.06 g, glyceryl palmitate 0.48 g, Tween-80 1.194 g, glycerol 0.274 g and added water to 30 mL by CCD-RSM. According to the optimized formulation, the encapsulation efficiency, particle size and Zeta potential were (94.06±1.54)%, (18.88±0.38)nm and (3.53±0.01)mV, respectively. The deviation was less than 5%. CONCLUSION The stable and ultra-small size E-SLN with high encapsulation efficiency could be obtained by combining pseudo-ternary phase diagrams and CCD-RSM.
关键词
伪三元相图 /
固体脂质纳米粒 /
星点设计效应面法 /
益康唑
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Key words
pseudo-ternary phase diagram /
solid lipid nanoparticle /
CCD-RSM /
econazole
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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
国家自然科学基金-河南联合基金重点项目资助(U1704283);河南省科技厅基础与前沿资助(142300410057)
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