目的 通过物理共混改性苯乙烯-异戊二烯-苯乙烯(SIS)型热熔压敏胶, 阐明改性热熔压敏胶的黏附性能、释药性能、经皮渗透性能与材料组成的关系, 分析pH对于改性热熔压敏胶释药和经皮渗透性能的影响。 方法 将苯乙烯-异戊二烯-苯乙烯与丙烯酸树脂尤特奇EPO共混制备两亲性热塑弹性体苯乙烯-异戊二烯-苯乙烯/丙烯酸树脂尤特奇EPO共混物(SEB), 使用扫描电子显微镜和原子力显微镜观测EPO共混物的微观形态;在EPO共混物中加入聚乙二醇(PEG)、矿物油、C5树脂和抗氧剂制备改性热熔压敏胶, 通过测定180°剥离强度和持黏力分析黏附性能;使用熊果苷等6种有效成分考察亲水/亲脂性药物的释放性能以及pH对释药性能变化的影响;考察压敏胶中芍药苷、盐酸青藤碱在皮肤表面弱酸性条件下的经皮渗透性能;使用1H 核磁共振波谱仪(1H-NMR)分析pH对压敏胶与药物分子间的相互影响。 结果 当苯乙烯-异戊二烯-苯乙烯-丙烯酸树脂尤特奇EPO=1∶2(w/w)时, 制备的苯乙烯-异戊二烯-苯乙烯/丙烯酸树脂尤特奇EPO共混物形成“双连续”结构, 在此基础上制备的改性热熔压敏胶具有较好的黏附性能, 实现了亲水/亲脂性药物的共同释放, 同时明显改善了亲水性药物的经皮渗透性能;改性热熔压敏胶显示出pH敏感性, 在弱酸性条件下丙烯酸树脂尤特奇EPO质子化, 导致药物快速释放和经皮渗透性提高。 结论 通过共混改性制备的pH敏感性热熔压敏胶适合于在经皮给药系统(TDDS)中应用。
Abstract
OBJECTIVE To Prepare amphiphilic hot-melt pressure sensitive adhesives(HMPSAs) and investigate the relationship among components, adhesion performance, drug release behavior of pH and transdermal permeation ability. METHODS Based on the blend of styrene-isoprene-styrene(SIS) thermoplastic elastomer and acrylic resin Eudragit EPO, following the addition of an appropriate amount of polyethylene glycol(PEG), mineral oil and C5 resin, the amphiphilic HMPSAs were prepared. The compatibility and micromorphology of SIS/EPO blends(SEBs) were analyzed with differential scanning calorimetry(DSC), atomic force microscopy(AFM) and scanning electron microscopy(SEM). The adhesive performance of HMPSAs was measured as 180° peeling strength and holding power.1H-nuclear magnetic resonance spectrometer(1H-NMR) was used to investigate the interaction between drugs and HMPSAs. The drug release behavior of arbutin and other five drugs were investigated, and the in vitro transdermal permeation was examined on mice′s skin to compare the transdermal permeation ability of sinomenine hydrochloride and paeoniflorin in different HMPSAs. RESULTS When the mass ratio of SIS to EPO was 1∶2, bicontinuous structure was formed. The HMPSAs could maintain good adhesion performance, achieve continual release of both hydrophilic and lipophilic drugs and exhibit good transdermal permeation ability for hydrophilic drugs as well. Due to the protonation of EPO, the amphiphilic HMPSAs exhibited higher release rate and transdermal permeation ability in weakly acidic condition. CONCLUSION The modified HMPSAs show good adhesive performance and pH sensitivity, so they are suitable for transdermal drug delivery system(TDDS).
关键词
苯乙烯-异戊二烯-苯乙烯 /
丙烯酸树脂尤特奇EPO /
弱酸性条件 /
药物释放 /
经皮
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Key words
SIS /
EPO /
weakly acidic condition /
drug release /
transdermal
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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
国家重大新药创制专项资金资助(2011ZX09501-001-02)
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