雌二醇阴道用生物黏附性温敏型凝胶的处方筛选及流变学考察

目的:研制雌二醇阴道用生物黏附性温敏型凝胶(E₂-VTISG),并进行热力学和流变学考察。方法:采用冷法工艺制备E₂-VTISG。采用倒试管法测定胶凝温度(T_gel),以T_gel为考察指标,泊洛沙姆P407,泊洛沙姆P188为主要影响因素,用星点设计-效应面法进行处方筛选。采用黏度计测定表观粘度,采用动态流变学实验测定温敏凝胶在相变过程中的流变参数。结果:雌二醇阴道用生物黏附性温敏型凝胶的最优处方的基质配比为P407:P188:甘油:PCP:尼泊金乙酯=18:2.96:5:0.2:0.2,实测胶凝温度为33.4℃。结论:星点设计-效应面法筛选E₂-VTISG处方预测性良好,流变学结果显示优化后的雌二醇温敏凝胶符合阴道局部用药要求。

Preparation and characterization of estradiol bioadhensive vaginal thermosensitive in situ gels

OBJECTIVE To prepare estradiol bioadhensive vaginal thermosensitive in situ gel (E₂-VTISG) and determine its thermodynamics and rheological properties.METHODS E₂-VTISG was prepared by cold dissolving method. Gel temperature (T_gel) was measured by tube inversion method. RSM plus CCD was used to design formulation, independent variables were contents of poloxamer 407 and poloxamer 188, and gelling temperature was a dependent variable. Apparent viscosity was determined by viscometer, rheological properties of E₂-VTISG by rotational rheometer.RESULTS Optimized formulation was confirmed as 18% P407, 2.96% P188, 5% glycerin, 0.2%PCP and 0.2% ethylparaben, and observed T_gel was 33.4℃.CONCLUSION Mathematical model developed by RSM plus CCD has good predictability. Optimized E₂-VTISG meets requirements for vaginal administration.