Drug Dynamics Institute, The University of Texas at Austin, 1 University Station, Mail Stop A1915, Austin, Texas 78712, USA.
Pharm Res. 2013 Mar;30(3):813-25. doi: 10.1007/s11095-012-0922-2. Epub 2012 Nov 15.
Inhalation of low-density porous particles enables deep lung delivery with less dependence on device design and patient inspiration. The purpose of this study was to implement Thin Film Freezing (TFF) to investigate a novel approach to dry powder inhalation.
Powders produced by TFF were evaluated for aerodynamic and geometric particle size by cascade impaction and laser light scattering, respectively. Density measurements were conducted according to USP methods and calculated using data from particle size measurements. Excipient inclusion and its effect on moisture sorption was measured by Dynamic Vapor Sorption (DVS).
TFF-produced brittle matrix powders were sheared apart into respirable microparticles using a passive DPI device, producing fine particle fractions (FPF) up to 69% and mass median aerodynamic diameters (MMAD) as low as 2.6 μm. Particles had a mean geometric diameter ranging from 25 μm to 50 μm and mass densities of approximately 0.01 g/cm(3). Powders were susceptible to moisture-induced matrix collapse, capillary forces and electrostatic charging; although formulations containing mannitol or no sugar excipient proved to be more robust.
Aerosolized brittle matrices produced by TFF may prove to be a useful platform for highly efficient pulmonary delivery of thermally labile, highly potent, and poorly soluble drugs.
吸入低密度多孔颗粒可以实现更深入的肺部输送，而对设备设计和患者吸气的依赖性较小。本研究的目的是采用薄膜冷冻（TFF）技术来探索干粉吸入的新方法。
通过级联撞击和激光光散射分别对 TFF 制得的粉末进行空气动力学和几何粒径评估。根据 USP 方法进行密度测量，并使用粒径测量数据进行计算。通过动态蒸汽吸附（DVS）测量赋形剂的包含及其对吸湿性的影响。
使用被动 DPI 装置将 TFF 制得的脆性基质粉末剪切为可吸入的微粉，产生高达 69%的细颗粒分数（FPF）和低至 2.6μm 的质量中值空气动力学直径（MMAD）。颗粒的平均几何直径范围为 25μm 至 50μm，质量密度约为 0.01g/cm³。粉末容易受到水分引起的基质塌陷、毛细作用力和静电充电的影响；尽管含有甘露醇或无糖赋形剂的配方表现出更强的稳定性。
TFF 制得的雾化脆性基质可能成为一种有用的平台，可用于高效肺部输送热敏、高活性和难溶性药物。
