星点设计-效应面法优化制备酒石酸溴莫尼定眼用温度敏感型原位凝胶

Optimization of the Preparation Technology of Brimonidine Tartrate Ophthalmic Thermosensitive in Situ Gel by Central Composite Design-response Surface Methodology

目的:制备酒石酸溴莫尼定眼用温度敏感型原位凝胶。方法:以泊洛沙姆407(P407)和泊洛沙姆188(P188)为凝胶基质,用冷溶法制备凝胶。采用星点设计-效应面法以相变温度(T1)和模拟泪液稀释后的相变温度(T2)为考察指标对P407、P188浓度进行二项式拟合,通过等高线重叠选择优化处方,对预测结果进行验证,并观察其外观、p H等。结果:优化后处方为50 ml凝胶中含有100 mg酒石酸溴莫尼定、26%P407、1.5%P188;所制制剂在室温(25℃)下为自由流动的液体,大于32℃时相变形成淡黄绿色透明凝胶;T1、T2分别为26.3、31.8℃,p H为6.41。结论:成功制得符合眼用标准的酒石酸溴莫尼定眼用温度敏感型原位凝胶。

OBJECTIVE： To prepare Brimonidine tartrate ophthalmic thermosensitive in situ gel. METHODS： Using poloxamer 407 （P407） and poloxamer 188 （P188） as gel matrix, the gel was prepared by cold-dissolving method. The binomial model of P407 and P188 concentrations were fitted by central composite design-response surface methodology using phase-transition tempera- ture （T1） and phase-transition temperature （T2） of simulated tear after diluted as index. The prescription was optimized with contour plot. The predictive data was validated, and the appearance and pH were observed. RESULTS： The optimized formulation was as follows： 100 mg brimonidine tartrate, 26% P407 and 1.5% P188 in 50 ml in situ gel; the preparation was free-flowing liquid at room temperature （25 ℃ ）, and converted to pistac transparent gels when the trial temperature was higher than 32℃ ; T1 and T2 were 26.3℃ and 31.8℃, and pH was 6.41. CONCLUSIONS： Brimonidine tartrate thermosensitve in situ gel which meets the requirements for ophthalmic application is prepared successfully.