苯甲酸利扎曲普坦鼻用温度-离子敏感型原位凝胶的制备及体外性质考察

Preparation and in-vitro Properties of Thermo-ion Sensitive In-situ Gel of Rizatriptan Benzoate for Intranasal Administration

目的:研制苯甲酸利扎曲普坦(RB)鼻用温度-离子敏感型原位凝胶,并考察其体外性质。方法:筛选合适的吸收促进剂,并对泊洛沙姆407及去乙酰结冷胶的最佳用量进行考察,制备RB温度-离子敏感型原位凝胶,对其胶凝温度、胶凝时间、胶凝强度、生物黏附力及体外释药特性进行测定。结果:最佳吸收促进剂为1.0%的羧甲基壳聚糖(CMCS),泊洛沙姆407用量为18%,去乙酰结冷胶用量为0.3%,胶凝温度为(32.6±0.3)℃,胶凝时间为(25.6±1.8)s,胶凝强度为(122.4±1.5)s,生物黏附力为(152.25±12.76)(×10^2dyne·cm^-2),体外释药符合Higuchi方程:Q=5.585 6t^1/2+0.326 0(r=0.994 2)。结论:RB鼻用温度-离子敏感型原位凝胶具有较好的温度、离子敏感性,并具有明显的缓释性。

Objective:To prepare thermo-ion sensitive gel of rizatriptan benzoate(RB)for intranasal administration and study the in vitro properties.Methods:The absorption enhancer was screened,and the optimal amounts of poloxamer 407 and deacetylated gellan gum were explored to prepare RB thermo-ion sensitive in-situ gel.The gelling temperature,gelling time,gelling strength,bio-adhesion and drug release in vitro were studied.Results:1.0%Carboxymethyl chitosan(CMCS)was used as the best absorption enhancer,and the amount of poloxamer 407 and deacetylated gellan gum was 18%and 0.3%,respectively.The gelling temperature,gelling time,gelling strength and bio-adhesion of the optimal formulation was(32.6±0.3)℃,(25.6±1.8)s,(122.4±1.5)s and(152.25±12.76)(×10^2dyne·cm^-2),respectively,and the in vitro drug release fit the following Higuchi equation:Q=5.585 6t^1/2+0.326 0(r=0.994 2).Conclusion:RB thermo-ion sensitive in-situ gel for intranasal administration shows promising thermo-ion sensitivity and notable sustained drug release.