用于肺部药物递送的纳米喷雾干燥粉雾剂  

Nano spray-dried powders for pulmonary drug delivery

作　　者：徐恩宇[1] 姜俊峰[2] 徐颖[3] 王洋[4] 李浩莹 

机构地区：[1]中国医科大学法医学院,沈阳110122 [2]辽宁师范大学化学化工学院,大连116029 [3]苏州大学分析测试中心,苏州215123 [4]中国医科大学公共基础学院,沈阳110122 [5]苏州惠仁生物科技有限公司,苏州215513

出　　处：《中国新药杂志》2016年第19期2262-2267,共6页Chinese Journal of New Drugs

基　　金：青年科学基金资助项目(21404120);中国医科大学校内基金资助项目(XZR20160033)

摘　　要：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 spray-dried（ NSD） drug particles with diameters in the range for efficient delivery to alveoli and investigate the effects of different excipients on the NSD powders to obtain dry powder inhalation（ DPI） with improved flowability,dispersibility,and deposition in lungs. Methods： The NSD powders loaded with salbutamol sulphate were prepared with lactose monohydrate（ LAC）,water soluble starch（ STA）,trehalose（ TRE） and-cyclodextrin（-CD） as excipients. The morphology of NSD powders was investigated using scanning electron microscope. The particle size and its distribution were determined by laser diffraction with dry dispenser. In vitro deposition performance and emitted dose of NSD powders were determined by a new generation of impactor（ NGI）. Results： The LAC-1 NSD powders demonstrated exact spherical shapes with smooth surface and strong adhesion,and the yield and volume average diameter were 12. 184 μm and 77. 7%,respectively. The powders generated a poor aerosolization performance with the emitted dose（ ED） and fine particle fraction（ FPF, 4. 46 μm） of only 78. 9% w / w and 11. 2%,respectively. However,the STA-,TRE- and-CD-modified NSD powders showed wrinkled surfaces with volume average diameters of 2. 2 - 2. 4 μm and yields of 80. 1% - 81. 6%.Unsurprisingly,these types of NSD powders demonstrated amazing EDs of 90% - 93% and remarkably augmented FPFs of 40% - 47%. Conclusion： NSD technology may improve the recovery of powders and obtain powders with smaller aerodynamic diameter,suggesting that NSD is a powerful technique to prepare respirable powders for efficient pulmonary drug delivery.

关 键 词：纳米喷雾干燥 硫酸沙丁胺醇 粉雾剂 辅料 

分 类 号：R943.4[医药卫生—药剂学]