目的 将酮洛芬制备成微乳凝胶以扩大其载药量并提高药物经皮透过率,考察其体外透皮特性。方法 通过绘制伪三元相图确定酮洛芬微乳区油相/表面活性剂比例范围,以离体大鼠皮肤的24 h累积渗透量及时滞为指标,采用星点设计-效应面法进行微乳凝胶处方优化,与市售凝胶对比透皮性能。结果 酮洛芬微乳最佳油相、表面活性剂及助表面活性剂分别为油酸、聚氧乙烯蓖麻油(EL-35)和乙醇,经星点设计实验优化的微乳处方为油酸1.35%,EL-35 10.8%,乙醇9%,其离体大鼠皮肤24 h累积渗透量562.82 μg·cm-2,是市售凝胶的1.35倍。结论 本实验制备的酮洛芬微乳凝胶渗透性能良好,为酮洛芬微乳凝胶的开发奠定基础。
Abstract
OBJECTIVE To prepare the ketoprofen microemulsion-based gel in order to expand its drug loading and increase the transdermal permeability. METHODS The proportion range of oil phase/surfactant in ketoprofen microemulsion were screened by the pseudo-ternary phase diagram. Optimization of formulation for microemulsion gels was conducted by central composite design-response surface methodology with the cumulative permeation quantity across in vitro rat skin and time-lag as evaluation indexes.The transdermal performance of self prepared gel was compared with the commercially available gel. RESULTS The optimal oil phase, surfactant and cosurfactant of ketoprofen microemulsion were oleic acid, polyoxy ethylene castor oil (EL-35) and ethanol, respectively.The optimal microemulsion formulation was 1.35% oleic acid, 10.8% EL-35, and 9% ethanol by central composite design experiment. The cumulative penetration quantity in 24 h reached 562.82 μg·cm-2 in vitro rat skin was 1.35 times as much as commercially available gel. CONCLUSION The ketoprofen microemulsion-based gel prepared in this study has good permeability, which lay the foundation for development of the gel.
关键词
酮洛芬 /
微乳凝胶 /
伪三元相图 /
体外透皮 /
星点设计-效应面法
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Key words
ketoprofen /
microemulsion-based gel /
pseudo-ternary phase diagram /
transdermal delivery in vitro /
central composite design-response surface methodology
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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
浙江省科技厅项目资助(2017C33147);浙江省神经精神疾病药物研究重点实验室资助(2019E10021)
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