氨茶碱/壳聚糖/β-环糊精肺吸入微球的工艺研究

Optimization on Theophylline/Chitosan/β-Cyclodextrin Microspheres for Pulmonary Drug Delivery

目的研究喷雾干燥法制备氨茶碱/壳聚糖/β-环糊精微球的制备工艺。方法采用正交设计优化喷雾干燥法制备氨茶碱/壳聚糖/β-环糊精微球的制备条件,考察氨茶碱在β-环糊精溶液中的溶解度以及氨茶碱/壳聚糖/β-环糊精微球的载药量、包封率、产率、含水率和外观形态等特性。结果氨茶碱的溶解度随温度和β-环糊精溶液浓度的增加而增加;根据载药量氨茶碱/壳聚糖/β-环糊精微球喷雾干燥的最佳工艺条件为A_1B_3C_1D_3,即进口温度为150℃,进料速度为8ml/min,空气流量为400L/h,壳聚糖分子量为130万;氨茶碱/壳聚糖/β-环糊精微球的载药量、包封率、产率和含水率分别为19.3%±0.5%,77.4%±0.6%,39.5%±1.0%,9.7%±0.7%;扫描电镜显示微球外观圆整,表面光滑或有少许皱褶;喷嘴直径为0.7mm时制得的微球粒径更小且较均一。结论采用正交设计优选了最佳制备工艺,其制得的氨茶碱/壳聚糖/β-环糊精微球具有较高的载药量、包封率、产率和较低的含水率,微球圆整,带少许皱褶,有望成为肺部吸入的理想药物载体。

Objective To optimize the spray drying technology of theophylline /chitosan/β-cyclodextrin microspheres .Methods The L9（3^4） orthogonal test was used to optimize the spray drying technology of theophylline /chitosan/β-cyclodextrin microspheres.The dissolubility of theophylline and drug loading ,encapsulation efficiency ,yield,water content and morphology of theophylline /chitosan/β-cyclo-dextrin microspheres were studied ,as the investigating indices .Results The dissolubility of theophylline was gradually increasing with the raise of temperature and the concentration of β-cyclodextrin .According to the drug loading ,and the optimum spray drying conditions of theo-phylline/chitosan/β-cyclodextrin microspheres were A 1 B3 C1 D3 ,namely the inlet gas temperature was 150℃,the feed flow rate was 8ml/min, the drying air flow was 400L/h and the molecular weight of chitosan was 13±10^5.The drug loading,encapsulation efficiency,yield,and water content of the theophylline/chitosan/β-cyclodextrin microspheres were 19.3%±0.5%,7.4%±0.6%,39.5%±1.0%,and 9.7%±0. 7%,respectively .Scanning electron micrograph showed that the microspheres were predominantly spherical with smooth surface or slightly wrinkled.The particle diameter of microspheres was smaller and uniform prepared by atomizing nozzles of 0.7mm.Conclusions These results indicate that theophylline/chitosan/β-cyclodextrin microspheres can be successfully prepared by spray drying method ,not only obtained higher drug loading ,but also higher encapsulation efficiency and yield .The lower water content in the microspheres is highly desirable .Micro-spheres are predominantly spherical with smooth surface or slightly wrinkled .It can serve as promising carrier in pulmonary drug delivery system.