天麻素淀粉微球的制备及其鼻黏膜黏附性与体外释药特性考察

Preparation of gastrodin starch microsphere and its nasal mucoadhesion and in vitro release characteristics

目的确定天麻素淀粉微球的处方工艺,并考察其鼻黏膜黏附特性与体外释药特性。方法采用复乳化交联法制备天麻素淀粉微球,以粒径、载药量和包封率为评价指标,通过单因素考察和均匀设计法优化天麻素淀粉微球的处方工艺;选择蟾蜍上颚黏膜为评价模型,黏膜平均滞留时间为指标,评价天麻素淀粉微球的黏膜黏附力;以天麻素原料药为对照,采用浆法,进行天麻素淀粉微球体外释药实验,计算累积释药率,并用不同释放模型拟合体外释药曲线,综合考察天麻素淀粉微球的释药特性。结果优化后的处方及制备工艺条件：天麻素2.0 g,淀粉4.5 g,液体石蜡100.0 m L,Span 80用量3.5 g,ECH 5.1 m L,制备温度40℃,搅拌速率1 000 r/min。天麻素淀粉微球的平均粒径为（47.69±1.92）μm,载药量和包封率分别为（9.78±0.70）%和（35.72±3.28）%;无黏附性粉末的平均滞留时间为（176.92±23.25）s,折算为人体鼻黏膜滞留时间仅为20~30 min,而天麻素淀粉微球的平均滞留时间延长至（944.33±68.29）s,折算为人体鼻黏膜滞留时间约为3 h;天麻素淀粉微球3 h累积释药达90%以上,释药过程符合Weibull模型,t50为40.08 min,t90为245.73 min。结论采用复乳化交联法,按所选处方工艺制备可得粒径均匀、载药量和包封率较高的天麻素淀粉微球;所得微球具有良好的黏膜黏附与缓释性能,可保证天麻素在微球鼻腔滞留期间平缓释放,并基本释药完全。

Objective To determine the prescription technology of gastrodin starch microsphere and investigate its nasal mucoadhesion and in vitro release characteristics. Methods Gastrodin starch microspheres were prepared by compound emulsion crosslinking method. According to the particle diameter, drug loading efficiency（DLE）, and entrapment efficiency（EE）, the best prescription technology was selected by using single-factor investigation and uniform design. Using toad palate mucosa as model and average residence time as indicator, mucoadhesion of gastrodin starch microsphere was evaluated. Using gastrodin API as a control, paddle method was applied to in vitro release test of gastrodin starch microspheres. The content of gastrodin was determined to calculate the cumulative release percentage. In addition, the curve of drug release in vitro was fitted with different release model to analyze the in vitro release characteristics of gastrodin starch microsphere in nasal cavity, synthetically. Results The optimum prescription and preparation technology of gastrodin starch microsphere were as follows： gastrodin 2.0 g, starch 4.5 g, liquid paraffin 100.0 m L, Span80 3.5 g, ECH 5.1 m L, preparation temperature 40 ℃, and rotational speed 1000 r/min. The particle diameter of gastrodin starch microsphere was（47.69 ± 1.92） μm, the DLE and EE of microsphere were（9.78 ± 0.70）% and（35.72 ± 3.28）%, respectively. It was about（176.92 ± 23.25） s that in adhesive powder resided in nasal cavity, which translated into human nasal residence time was just 20—30 min, while the average residence time of gastrodin starch microspheres was extended to（944.33 ± 68.29） s, translated into human nasal residence time was about 3 h. The cumulated release percent of gastrodin starch microspheres was more than 90% in 3 h. Compared with other in vitro release models, Weibull model was the fittest model to gastrodin starch microspheres, the t50 of gastrodin starch microspheres was 40.08 min, and t90 was 245.73 min. Conclusion Gastrodin starch microspheres prepared with optimum prescription technology have uniform particle diameter, high DLE and EE. Microspheres have good mucoadhesion and sustained release, ensure that gastrodin release gently and completely during the nasal retention period.