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目的:采用纳米喷雾干燥(NSD)技术制备粒径在理想肺吸入尺度范围内的纳微颗粒,并系统考察不同辅料对NSD颗粒的影响,以获得具有良好吸入效率的NSD粉雾剂。方法:以一水合乳糖(LAC)、可溶性淀粉(STA)、海藻糖(TRE)和-环糊精(-CD)为辅料,制备硫酸沙丁胺醇的NSD颗粒。采用扫描电镜观察NSD颗粒形貌;激光粒度仪表征NSD颗粒粒度分布情况;新一代药用撞击器测定NSD颗粒的排空率及有效部位沉积率。结果:LAC-1 NSD颗粒呈光滑圆球状、黏附力强,产率为77.7%,体积平均粒径12.184μm,用其制得的粉雾剂排空率(ED)和微颗粒(<4.46μm)比例(FPF)为78.9%和11.2%;而采用STA-,TRE-和-CD修饰的NSD颗粒表面褶皱、分散性良好,体积平均粒径、产率、ED和FPF分别在2.2~2.4μm,80.1%~81.6%,90%~93%和40%~47%范围内。结论:采用NSD技术可显著提高粉雾剂的回收率,可获得具有更小空气动力学直径的药物颗粒,这展现了NSD技术在获得和优化纳微干粉颗粒以实现药物高效肺吸入方面的巨大潜力。
OBJECTIVE: To prepare nano-particles with particle size within the range of ideal pulmonary ingestion by nano-spray-drying (NSD) technique and systematically investigate the effect of different excipients on NSD particles to obtain NSD powder aerosol with good inhalation efficiency. Methods: Salbutamol sulphate (NSD) granules were prepared with lactose monohydrate (LAC), soluble starch (STA), trehalose (TRE) and cyclodextrin (-CD) as excipients. The morphology of NSD particles was observed by scanning electron microscopy. The particle size distribution of NSD particles was characterized by laser particle sizer. A new generation of medical impactor was used to determine the voidage and deposition rate of NSD particles. Results: The particles of LAC-1 NSD showed a smooth spherical shape with strong adhesion and a yield of 77.7%. The volume average particle size was 12.184μm. ) Ratio (FPF) of 78.9% and 11.2%, respectively. However, the average particle size, yield, ED and FPF of NSD particles modified with STA-, TRE- and -CD were well distributed at 2.2-2.4μm , 80.1% -81.6%, 90% -93% and 40% -47%. CONCLUSIONS: The use of NSD technology to significantly increase the recovery of powder aerosols and to obtain drug particles with smaller aerodynamic diameters demonstrates the tremendous volume of NSD technology in obtaining and optimizing nanoparticulate dry powder particles for efficient drug pulmonary ingestion potential.