布地奈德4种直肠给药制剂体外释放和流变学特征研究

Study on in vitro Release and Rheological Properties of Four Rectal Administration Preparations Containing Budesonide

目的:评价布地奈德4种直肠给药制剂的体外释放和流变学特性,预测布地奈德脂质体温敏凝胶的体内释放行为。方法:采用乙醚注入法制备脂质体,以泊洛沙姆407、泊洛沙姆188和HPMC制备布地奈德脂质体温敏凝胶,并制备布地奈德的普通灌肠剂、脂质体制剂、温敏凝胶制剂;采用改良Franz扩散池法,测定4种直肠给药制剂的体外释放参数并绘制累计释放曲线;以旋转黏度计测定不同条件下温敏凝胶和脂质体温敏凝胶的静态流变学的变化规律。结果:布地奈德脂质体温敏凝胶释药性能最好,温敏凝胶次之,脂质体和普通灌肠液释药性能较差且无显著差别;在常温下,温敏凝胶和脂质体温敏凝胶均为牛顿流体,在30~35℃时发生相变黏度上升,在体内温度、pH、电解质等条件下脂质体温敏凝胶表现更佳。结论:布地奈德脂质体温敏凝胶可充分发挥直接直肠给药的优势,可快速贴附于直肠黏膜释药,为布地奈德新型直肠用制剂的研究提供参考。

Objective:To evaluate the in vitro release and rheological properties of budesonide 4 rectal preparations,and to predict the release behavior of budesonide liposomal temperature-sensitive gel in vivo.Methods:Liposomes were prepared by ether injection method.Budesonide liposomal temperature-sensitive gel was prepared with Poloxamar 407,Poloxamar 188 and HPMC as the matrix,and the common enema,liposomal preparation and temperature-sensitive gel of budesonide were prepared.The in vitro release parameters of four rectal preparations were determined by modified Franz diffusion cell method,and the cumulative release curves were drawn.The static rheology of temperature-sensitive gel and liposomal temperature-sensitive gel under different conditions was determined in a rotational viscometer.Results:The in vitro release performance of budesonide liposomal temperature-sensitive gel was the best,followed by that of temperature-sensitive gel,while that of liposomes and common enema was poor,and there was no significant difference between them.At room temperature,temperature-sensitive gel and liposomal temperature-sensitive gel were all Newton fluids.The viscosity of phase change increased at 30-35 ℃,and the liposomal temperature-sensitive gel was better under the conditions of body temperature,pH and electrolyte,etc.Conclusion:Budesonide liposomal temperature-sensitive gel can bring the superiority of rectal administration into full play,and can be quickly attached to rectal mucosa for drug release.The study provides reference for the further exploration of new rectal preparations containing budesonide.