硝酸毛果芸香碱眼用原位凝胶的制备和评价  

Preparation and evaluation of pilocarpine nitrate in situ gel for ophthalmic use

作　　者：朱静[1,2] 姜锋[2] 阎卉[2] 王成港[2] 王春龙[2] 

机构地区：[1]天津医科大学,天津300070 [2]天津药物研究院,天津300193

出　　处：《中草药》2010年第5期720-724,共5页Chinese Traditional and Herbal Drugs

摘　　要：目的以硝酸毛果芸香碱为模型药,研究温度敏感型原位凝胶对药物眼部滞留和体外释放的影响。方法以泊洛沙姆407、188为凝胶剂,以卡波姆974P为增黏剂,制备眼用温敏型原位凝胶。考察原位凝胶的流变学性质;采用改良Franz扩散池法研究凝胶的体外释药行为。结果流变学测定结果显示原位凝胶在室温状态下为物理缠结的聚合物溶液,在眼表温度下转变为次级键网状结构。泊洛沙姆188、卡波姆974P的加入均可延缓药物的释放,二者对凝胶的黏性模量G"的影响不同。原位凝胶在4h内缓慢释放药物,释放曲线符合Higuchi方程(r=0.9923)。结论通过调节泊洛沙姆407和188的比例,可得到具有适宜溶液-凝胶转变温度和良好释药特性的原位凝胶。流变学结果提示原位凝胶的眼部滞留能力强于普通滴眼液,是一种具有研究前景的给药系统。Objective To develop and charaterize a series of Poloxamer- and Carbopol-based in situ gel for ophthalmic use as to enhance the ability of drug to retain in eyes and delay drug release. Methods The gel was prepared using Poloxamer 407/188 and Carbopol 974P as gelling agent and viscosity enhancer, respectively. Rheological characteristics were evaluated and behaviour of drug release in vitro was investigated by modified Franz diffusion ceils. Results The rheological study indicated that the gel was physical- ly entangled polymer solutions at 20 ℃ and then converted into a network structure with secondary bonds at 35 ℃. The gel released the drug molecules slowly in 4 h. The best fit model was Higuchi matrix model （r=0. 992 3）. Formulations consisting of Poloxamer 188 and Carbopol 974P were proved to be able to decrease the drug release speed efficiently. The impact on elastic modulus G″ of the gel caused by those two were different. Conclusion An in situ gel with suitable sol-gel transition temperature and satisfactory release pattern could be achieved by adjusting the ratio of Poloxamer 407 to Poloxamer 188. The developed formulations have the ability to prolong the ocular residence time, which suggests it may be a new durg delivery system with bright future.

关 键 词：硝酸毛果芸香碱 眼用原位凝胶 温敏型 流变学 溶液-凝胶转变温度 体外释放 

分 类 号：R286.02[医药卫生—中药学]