伊曲康唑阴道用温度敏感原位凝胶的制备及性能研究  

Preparation and characteristics of itraconazole vaginal thermosensitive in situ gels

作　　者：叶小翠[1] 欧金来 洪宝贤[1] 冯翠娟[1] 李沙[1] 

机构地区：[1]暨南大学药学院药剂学教研室,广州510632

出　　处：《中南药学》2014年第6期551-556,共6页Central South Pharmacy

基　　金：广州市科技计划(No.11C32070756)

摘　　要：目的研制伊曲康唑阴道用温度敏感原位凝胶并考察其性能。方法以伊曲康唑(ITZ)为模型药物,泊洛沙姆为基质采用冷溶法制备伊曲康唑阴道用温度敏感原位凝胶(TISG)。采用试管倒转法测定胶凝化温度(Tg),星点设计-效应面法优化ITZ-TISG处方工艺,旋转流变仪测定其流变学特性。并采用无膜溶出法考察ITZ-TISG溶蚀释药特性。结果通过星点设计-效应面法筛选出最佳处方为16.3%泊洛沙姆407、1.5%泊洛沙姆188、0.31%海藻酸钠。采用试管倒转法测得最优处方所制备的ITZ-TISG的Tg为25℃,经模拟阴道液稀释后的Tg为35℃,与流变仪测得的结果基本一致。在35℃时,ITZ-TISG经阴道模拟液稀释后仍具有较强的黏弹特性。ITZ-TISG的体外溶蚀释药符合零级动力学模型。结论星点设计-效应面法优化ITZTISG处方所建立的模型具有良好的预测性。所优化的ITZ-TISG在给药时流动性好,给药后可在阴道生理温度下快速胶凝形成原位凝胶,并具有缓慢溶蚀释放药物的特性,可满足阴道用药设计要求。Objective To prepare itraconazole vaginal thermosensitive in situ gel（ITZ-TISG） and to determine its properties. Methods Poloxamer was used as matrix. ITZ-TISG was prepared by cold dissolving method. The gel temperature（Tg） was measured by tube inversion method. The formulation was optimized by central composite designresponse surface method. The rheological properties of ITZ-TISG were determined by rotational rheometer. The gel erosion and drug release were measured by membraneless dissolution method. Results The optimized formulation contained 16.3% poloxamer 407, 1.5% poloxamer188, and 0.31% sodium alginate. The gel temperature of optimized ITZ-TISG before and after the simulated vaginal fluid dilution was 25 ℃ and 35 ℃ by tube inversion measurement, which was similar to that measured by rheometer. After the dilution with simulated vaginal fluid, ITZ-TISG still showed strong viscoelastic properties at 35 ℃. The gel erosion and drug release behavior of ITZ-TISG in vitro followed the zero-order kinetic process. Conclusion The mathematical model developed by central composite designresponse surface method can predic well. The optimized ITZ-TISG may flow well during administration, and quickly form in situ gel under vaginal physiological temperature after administration. The gel displays sustained erosion and release. ITZ-TISG meets the design requirement for vaginal administration.

关 键 词：伊曲康唑 泊洛沙姆 温度敏感原位凝胶 星点设计-效应面法 流变学 体外溶蚀释药 

分 类 号：R944[医药卫生—药剂学]