星点设计-效应面法优化托吡卡胺温敏型原位凝胶处方

Optimization of Tropicamide Ophthalmic Thermosensitive in Situ Gel by Central Composite Design-response Surface Methodology

目的:优化托吡卡胺眼用温敏型原位凝胶的制备工艺。方法:采用星点设计法考察温敏材料泊洛沙姆407和泊洛沙姆188质量分数对指标相变温度的影响,并以相变温度(T1)和模拟泪液稀释后的相变温度(T2)为指标对结果进行模型拟合;采用效应面法优化处方并进行验证,测定300 min内的体外累积释放度。结果:泊洛沙姆407和泊洛沙姆188质量分数分别为20%、5%,以T1和T2为指标进行多元线性回归的相关系数分别为0.918 7、0.889 9;效应面法优化处方的实测值与预测值偏差绝对值均<5%,300 min内的体外累积释放度为65%。结论:星点设计-效应面法所建立的模型实现了该眼用温敏型原位凝胶的处方优化,数学模型预测性良好。

OBJECTIVE： To optimize the preparation technology of Tropicamide ophthalmic thermosensitive in situ gel. METH- ODS： Central composite design was used to observe the iafluenee of the amount of P407 and P188 on the phase-transition tempera- ture; the multi-linear regression model was fitted using phase-transition temperature （TL） and phase-transition temperature of sam- ples after diluted with simulated tears （T2） as index. Optimized formulation was selected and validated by response surface method- ology, and accumulative release rate in vitro was determiJled within 300 min. RESULTS： The amount of P407 and P188 were 20% and 5%; the correlation coefficient of multi-linear regression model were 0.918 7 and 0.889 9 using T1 and T2 as index, respective- ly. The absolute values of deviations between measured ,zalue and predicted value were all lower than 5%, and accumulative re- lease rate in vitro was 65 % within 300 rain. CONCLUSICNS： The optimization of the ophthalmic thermosensitive in situ gel formu- lation can be achieved by central composite design-respone surface methodology with good estimation.