利巴韦林温度-离子敏感型鼻用原位凝胶喷雾剂的制备及体外性质考察

目的制备具有适宜临界相变温度和临界相变阳离子强度,及适宜的喷雾粒度、使用方便、缓慢释放药物的温度-离子敏感复合型鼻用原位凝胶。方法以临界相变温度、临界相变阳离子强度、喷雾粒度为考察指标筛选温敏及离子敏材料的用量,制备利巴韦林温度-离子敏感复合型原位凝胶。以透析袋法评价该复合凝胶的凝胶外排水量、溶蚀速率、体外释放度,并以断裂距离为指标评价凝胶的黏膜黏附力。结果以质量分数为0.3%的去乙酰化结冷胶和质量分数为18.0%的泊洛沙姆407制备的温度-离子敏感复合型原位凝胶,临界相变温度为32.6℃,临界相变阳离子强度为93.4 mmol.kg-1,喷雾粒度为68.0μm,凝胶外排水质量分数为(13.8±0.8)%,溶蚀速度常数为1×10-4min-1,断裂距离为(1.60±0.06)mm。该混合凝胶具有良好的体外缓释特征。结论该复合型原位凝胶剂适宜作为水溶性药物的鼻用缓释载体。

Preparation and in vitro evaluation of thermo- and ion- sensitive in situ gels of vibavirin via intranasal administration

Objective To prepare thermo-ion-sensitive in situ gels of vibavirin, which possess favorable phase transition temperature, phase transition cationic intensity, spray particle size and sustained-release properties. Methods Concentrations of deacetylated gellan gum and poloxamer 407 in the in situ gel were decided by investigating the phase transition temperature, phase transition cationic intensity and spray particle size. The amount of drained water after gels gelated, gels corrosion rate, in vitro vibavirin release profile and mucoadhesive properties were evaluated. Results The in situ gel was prepared with 0.3 %（w） deacetylated gellan gum and 18.0 %（w） poloxamer 407, with phase transition temperature of 32.6 ℃, phase transition cationic intensity of 93.4 mmol·kg-1, spray particle size of 68 μm, the amount of drained water after gels gelated of (13.8±0.8) %, gel corrosion rate of 0.1×10-3, deformation to failure of (1.60±0.06) mm. Meanwhile, the drug release profile of this in situ gel was favorable. Conclusions The in situ gel with 0.3 %（w） deacetylated gellan gum and 18.0 %（w） poloxamer 407 might be a suitable nasal delivery system for sustained-release of hydrophilic drugs.