星点设计-效应面法优化托吡卡胺温敏型原位凝胶处方

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（T。）和模拟泪液稀释后的相变温度（L）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300rain内的体外累积降放度。结果：泊洛沙姆407和泊洛沙姆188质量分数分别为20％、5％，以T·和Tz为指标进行多元线性回归的相关系数分别为（1．9187、0．8899；效应面法优化处方的实测值与预测值偏差绝对值均〈5％，300min内的体外累积释放度为65％。结论：星点设计一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。

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

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.