秦皮温敏眼用即型凝胶的制备与体内外研究

Preparation,in Vitro and in Vivo Studies of Fraxini Cortex Thermosensitive in-Situ-Forming Eye Gel

目的研究秦皮温敏眼用即型凝胶的体外性质,刺激性,药物释放机制及眼部消除动力学。方法采用无膜溶蚀模型研究药物的释放机制。以凝胶外观、pH值、胶凝温度、含量等变化为指标考察强光照射、冷冻及加速实验条件下凝胶的稳定性。采用Draize眼部刺激性试验评价单次和多次给药后凝胶对兔眼的刺激性。使用统计矩法评价了药物在家兔眼部的消除动力学特征。结果该制剂稳定性好,无刺激,药物释放主要受胶凝溶蚀控制,符合零级动力学过程。药动学结果显示,凝胶组AUC和MRT明显高于滴眼液组(P<0.05)。结论秦皮温敏眼用即型凝胶可明显延长药物在眼部的滞留时间,提高药物的生物利用度,展现出良好的眼部应用前景。

OBJECTIVE To study on characterization, irritation, the release mechanism and the elimination kinetics of Fraxi- ni Cortex thermosensitive in-situ-forming eye gel （FC-ISG）. METHODS The non-membrane dissolution model was used to ob- serve the release mechanism of FC-ISG. The stabilities of FC-ISG were investigated under following circumstances ： bright fight, freeze test and accelerating test. Single-dose and multiple-dose irritations of FC-ISG were evaluated by draize test. The elimination kinetics of FC-ISG were analyzed by non-compartment model. RESULTS FC-ISG showed good stability and non-stimulation to rabbit eyes. Drug release from FC-ISG was completely controlled by gel erosion, the release kinetics was coincided with zero-level release. AUC and MRT in FC-ISG group were significantly higher than those in control group （ P 〈 0.05 ）. CONCLUSIONS FC-ISG can improve the bioavailability of drug by prolonging the residence retention time of drug in cornea. FC-ISG shows a great potential in ocular application.