苯甲酸利扎曲普坦鼻用温度-离子敏感型原位凝胶的体外溶蚀特性及安全性评价
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摘要
目的:对苯甲酸利扎曲普坦(RB)鼻用温度-离子敏感型原位凝胶的体外溶蚀及安全性进行研究。方法:采用体外振荡法检测RB鼻用温度-离子敏感型原位凝胶的基质溶蚀及药物释放特性。以生理盐水为正常对照,1%去氧胆酸钠为阳性对照,观察RB鼻用温度-离子敏感型原位凝胶对蟾蜍上腭纤毛运动及形态的影响,以及对大鼠鼻黏膜形态的影响。结果:RB鼻用温度-离子敏感型原位凝胶的基质溶蚀及释药均为零级动力学过程,溶蚀方程为A=0.092 2t+0.198 8(r=0.998 6),释药方程为Q=0.246 0t+1.846 2(r=0.997 7),且两者有明显的线性相关性:Q=0.352 5A-0.424 8(r=0.999 0)。与正常对照组相比,RB鼻用温度-离子敏感型原位凝胶对蟾蜍纤毛运动能力无显著影响(P>0.05),且纤毛分布均匀,排列整齐,同时对大鼠鼻黏膜无明显的毒性。结论:RB从原位凝胶中的释放主要受凝胶溶蚀控制,同时具有良好的鼻用安全性。
Objective: To study the in vitro erosion and safety of rizatriptan benzoate( RB) thermo-ion sensitive in-situ gel for intranasal administration.Methods: Horizontal vibration method was used to study the base erosion and drug release of RB thermo-ion sensitive in-situ gel. Saline as the normal control and 1% sodium deoxycholate as the positive control,the influences of RB thermo-ion sensitive in-situ gel on the movement and morphology of toad palate cilia and the mucosal morphology of rats were explored. Results:The base erosion and drug release of RB thermo-ion sensitive in-situ gel both fitted zero-order kinetics with the equation of A = 0.092 2 t+0.198 8( r = 0.998 6) and Q = 0.246 0 t+1.846 2( r = 0.997 7),respectively,and the linear relationship between them was as the following equation: Q = 0.352 5 A-0.424 8( r = 0.999 0). Compared with the normal control group,RB thermo-ion sensitive in-situ gel showed no significant influences on the movement and morphology of toad palate cilia with uniform distribution and neat arrangement( P>0.05),and exhibited no obvious toxicity on the nasal mucosa of rats. Conclusion: RB release is mainly controlled by the erosion of the base of thermo-ion sensitive in-situ gel with promising safety for nasal administration.
Objective: To study the in vitro erosion and safety of rizatriptan benzoate( RB) thermo-ion sensitive in-situ gel for intranasal administration.Methods: Horizontal vibration method was used to study the base erosion and drug release of RB thermo-ion sensitive in-situ gel. Saline as the normal control and 1% sodium deoxycholate as the positive control,the influences of RB thermo-ion sensitive in-situ gel on the movement and morphology of toad palate cilia and the mucosal morphology of rats were explored. Results:The base erosion and drug release of RB thermo-ion sensitive in-situ gel both fitted zero-order kinetics with the equation of A = 0.092 2 t+0.198 8( r = 0.998 6) and Q = 0.246 0 t+1.846 2( r = 0.997 7),respectively,and the linear relationship between them was as the following equation: Q = 0.352 5 A-0.424 8( r = 0.999 0). Compared with the normal control group,RB thermo-ion sensitive in-situ gel showed no significant influences on the movement and morphology of toad palate cilia with uniform distribution and neat arrangement( P>0.05),and exhibited no obvious toxicity on the nasal mucosa of rats. Conclusion: RB release is mainly controlled by the erosion of the base of thermo-ion sensitive in-situ gel with promising safety for nasal administration.
引文
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2 肖林林,谢老智,黄小英,等.鼻腔给药应用于脑靶向递药系统的研究概况[J].江西中医药,2017,48(3):71-74
3 何文,周晶晶,郭咸希.眼用N-三甲基壳聚糖包衣胰岛素纳米脂质体原位凝胶的研制及体外释药研究[J].广东药学院学报,2013,29(1):1-5
4 辛月. HPLC法测定苯甲酸利扎曲普坦片中主药的含量[J].中国药房,2007,18(13):1017-1018
5 蔡鸿生,吴东方,何文,等.阿司匹林淀粉微球对纤毛毒性的评价[J].中国医院药学杂志,2001,21(5):261-262
6 陈新梅,朱家壁,孙卫东,等.吸收促进剂对人参皂苷Rg1鼻腔吸收的促进作用及鼻腔毒性[J].药学学报,2006,41(2):149-155
7 李新方,李现贵,马志强,等.薄荷脑鼻腔原位凝胶剂的制备及安全性研究[J].药学实践杂志,2017,35(4):321-325