具有复合功能的肺吸入粉雾制剂的研究

Multifunctional dry powder formulations for pulmonary drug delivery

目的：获得既具有优异的肺部递送效率又能够实现药物在肺部缓释的新型复合功能肺吸入粉雾剂。方法：选用3种不同相对分子质量的壳聚糖为载体，利用喷雾干燥技术制备高分散性的硫酸沙丁胺醇粉雾剂，乳糖制剂做参比。采用扫描电镜观察粉粒表面形态；激光粒度仪检测粒径大小和分布情况；新一代药用撞击器测定粉雾剂的排空率及有效部位沉积率；采用“桨法”初步考察粉雾剂缓释能力。结果：壳聚糖载体粉雾剂粉粒表面褶皱，体积平均粒径小于4．5μm，乳糖载体制剂大于16．4μm；壳聚糖载体中药物的有效部位沉积率55％～65％，比乳糖制剂（11％）有显著性提高；在1min内药物经乳糖载体可释放出80％，壳聚糖载体中释放出等量药物需20min，说明壳聚糖粉雾剂缓释效果明显。结论：壳聚糖可显著提高粉雾剂的分散性和有效部位沉积率，还可制备成缓释粉雾剂用于治疗肺部疾病。

Objective： To develop muhifunctional spraydried powders with enhanced dispersibility and sustained drug release characteristics for pulmonary drug delivery. Methods： Three groups of chitosan with differ ent molecular weights were employed as the excipients to prepare spraydried powders containing the model drug salbutamol sulfate （SS） or lactoseSS （control）. The morphology of spraydried particles was investigated using a scanning electron microscope. Particle size and its distribution were determined by laser diffraction with a dry dis penser. Invitro deposition performance of spraydried powders was determined by a new generation of impactor （NGI）. The invitro dissolution of model drug released from the dry powders was investigated using a modified USP II dissolution apparatus. Results： The spraydried chitosanSS powders showed wrinkled surfaces with an average size of 4.5μm, which is much smaller than that of the lactoseSS spraydried smooth powders （ 16.4 μm）. The spraydried chitosanSS powders showed a dramatically increased predominate deposition in the target sites with fractions of 55% 65% , which is much higher than that （11.2%） of the lactoseSS powders. Additionally, the time for release of 80% model drug was 1 rain for lactoseSS powders, but was 20 rain for chitosanSS powders, suggesting a sustained drug release from chitsonmodified spraydried powders. Conclusion： Chitosan can not only enhance the dispersibility and lung deposition of spraydried powders but also elongate the time of drug release,which is beneficial for the treatment of lung diseases.