双氯芬酸钠眼用温敏凝胶的处方优化及体外释放  

Optimization and evaluation of ophthalmic thermosensitive in situ gels of diclofenac sodium

作　　者：鞠凤阁[1] 朱照静[1] 王丽娟[1] 马俐丽[1] 

机构地区：[1]重庆医科大学药学院,重庆400016

出　　处：《中国医院药学杂志》2009年第7期541-545,共5页Chinese Journal of Hospital Pharmacy

摘　　要：目的:制备双氯芬酸钠(DS)眼用温敏凝胶并考察其体外溶蚀与药物释放行为。方法:采用试管倒转法测定胶凝温度;以泊洛沙姆P407和P188为温敏凝胶材料,模拟泪液稀释前后的胶凝温度为评价指标,采用星点设计-效应面法对DS眼用温敏凝胶处方进行优化;采用无膜溶出法模拟眼部生理环境,考察凝胶的体外溶蚀和药物释放行为。结果:DS眼用温敏凝胶的胶凝温度随P407浓度增大而降低,随P188浓度增加先升高后降低;模拟泪液的稀释可使胶凝温度升高;星点设计-效应面法筛选出的DS眼用温敏凝胶最佳处方为21%P407和5%P188;凝胶溶蚀速率决定药物的释放速率,二者均遵循零级动力学方程。结论:星点设计-效应面法可用于眼用温敏凝胶处方的优化,所建立模型具有较好的预测能力和实用性;处方中含21%P407和5%P188的DS眼用温敏凝胶的性质满足眼部用药的设计要求,有望在临床中获得应用。OBJECTIVE To screen an optimal formulation of ophthalmic thermosensitive in situ gels of diclofenac sodium （DS）. METHODS Tube-reverse method was carried out to evaluate the gelation temperature. The formulation was optimized using central composite design-response surface methodology （RSM plus CCD）. The effects of two independent variables, poloxamer P407 and P188, were evaluated. Response variables selected in the research were the gelation temperatures before and after simulated tear fluid dilution. Quadratic models were used to estimate the relationship between the dependent and inde- pendent variables, and to delineate RSM and overlay contour plots in order to select the optimal formulation. The rates of gel dissolution and drug release of the optimized formulation were also investigated with a membrane-less dissolution model. RESULTS Four optimal formulations were prepared according to the optimized area predicted by quadratic model and evaluated. The observed values agreed well with model predicted values. The in vitro release experiment showed that the release of DS from poloxamer gels followed zero-order kinetics and correlated well with the weight percentage of gel dissolved, indicating a dissolution-controlled release mechanism. CONCLUSION RSM plus CCD was successfully used to optimize the formulation of thermosensitive in situ gels of DS. An optimized formulation containing 21%P407 and 5%P188 showed better thermosensitive in situ gel characteristics and great potential in ophthalmic application.

关 键 词：眼用温敏凝胶 星点设计 效应面法 凝胶溶蚀 体外释放 

分 类 号：R944[医药卫生—药剂学]