阿昔洛韦眼用pH敏感原位凝胶剂的制备和评价  

Preparation and evaluation of ophthalmic pH sensitive in-situ gel of acyclovir

作　　者：李馨儒[1] 雷耀龙[2] 沈传勇 周艳霞[1] 陈星伟[1] 刘艳[1] 

机构地区：[1]北京大学药学院药利学系,北京100191 [2]中华人民共和国国家知识产权局专利局,北京100088 [3]国家良品药品监督管理局药品认证管理中心,北京100061

出　　处：《中国新药杂志》2009年第24期2360-2364,共5页Chinese Journal of New Drugs

摘　　要：目的:制备并评价阿昔洛韦眼用pH敏感原位凝胶剂。方法:用旋转粘度计测定不同pH值、不同温度下制剂的粘度,考察制剂的流变学特征;用荧光示踪法测定凝胶剂的眼部滞留时间;采用同体自身对照法考察凝胶剂的眼部刺激性;采用Franz扩散池法考察了制剂的离体角膜渗透性能,采用HPLC法测定渗透药量。结果:所制备的阿昔洛韦原位凝胶剂为假塑性流体,对兔眼无刺激;该原位凝胶剂的眼部滞留时间为(22.4±1.4)min,比阿昔洛韦滴眼液增加4.6倍;兔离体角膜渗透实验结果表明,该原位凝胶剂在给药0.25h以后各时间点的累积透过量均高于阿昔洛韦滴眼液,角膜有一定的贮库作用。结论:阿昔洛韦原位凝胶剂的刺激性低,眼部滞留时间长,具有一定的缓释效果。Objective：To prepare acyclovir （ACV） pH sensitive in-situ gel and evaluate its behavior in vitro. Methods ： Rheological quality was investigated by effect of pH and temperature on viscosity of in-situ gel. Ocular residence time was determined by Fluorescence-labeled technique. Ocular safety was evaluated by ocular irritation test in rabbit according to Guiding Principles fbr Stimulatiou, Allergy and Hemolysis of New Drug. The cornea permeation test of ACV pH sensitive in-situ gel was studied using Franz diffusion cell with rabbit corneas, The permeation amount of ACV was determined by high performance liquid chromatography. Results：The rheologieal curve demonstrated that the ACV pH sensitive in-situ gel represented pseudoplastic tlow type. Both ACV pH sensitive insitu gel and ACV eye-drop had no irritation after ocular administration. The ocular residence time of ACV pH sensitive in-situ gel （22.4 ± 1.4 rain） were as 5.6 times as that of ACV eye-drop （4.0 ± 0.5 rain）. The perfusion through the isolated rabbit cornea demonstrated that the drug concentration of aqueous humour for ACV in-situ gel was higher than that for eye drop after 0.25 h of ocular administration and the cornea acted as drug reservoir at some extent. Conclusion：As a liquid ophthalmic delivery systems, ACV pH sensitive in-situ gel could undergo in-situ phase transition to form gels which decreased drug release rate,and showed characteristics of sustained release.

关 键 词：阿昔洛韦 PH敏感 原位凝胶 

分 类 号：R943.4[医药卫生—药剂学] R978.7[医药卫生—药学]