Virginia Commonwealth University, Richmond, Virginia, USA.
Pharm Res. 2012 Mar;29(3):707-21. doi: 10.1007/s11095-011-0596-1. Epub 2011 Sep 27.
The objective of this study was to investigate the hygroscopic growth of combination drug and excipient submicrometer aerosols for respiratory drug delivery using in vitro experiments and a newly developed computational fluid dynamics (CFD) model.
Submicrometer combination drug and excipient particles were generated experimentally using both the capillary aerosol generator and the Respimat inhaler. Aerosol hygroscopic growth was evaluated in vitro and with CFD in a coiled tube geometry designed to provide residence times and thermodynamic conditions consistent with the airways.
The in vitro results and CFD predictions both indicated that the initially submicrometer particles increased in mean size to a range of 1.6-2.5 μm for the 50:50 combination of a non-hygroscopic drug (budesonide) and different hygroscopic excipients. CFD results matched the in vitro predictions to within 10% and highlighted gradual and steady size increase of the droplets, which will be effective for minimizing extrathoracic deposition and producing deposition deep within the respiratory tract.
Enhanced excipient growth (EEG) appears to provide an effective technique to increase pharmaceutical aerosol size, and the developed CFD model will provide a powerful design tool for optimizing this technique to produce high efficiency pulmonary delivery.
本研究旨在通过体外实验和新开发的计算流体动力学（CFD）模型，研究组合药物和辅料亚微米气溶胶的吸湿性生长，以用于呼吸药物输送。
使用毛细管气溶胶发生器和 Respimat 吸入器，实验性地生成亚微米级的组合药物和辅料颗粒。在设计为与气道保持一致的停留时间和热力学条件的螺旋管几何形状中，对气溶胶的吸湿性生长进行了体外评估和 CFD 预测。
体外结果和 CFD 预测都表明，对于非吸湿性药物（布地奈德）和不同吸湿性赋形剂的 50:50 组合，最初的亚微米颗粒的平均粒径增加到 1.6-2.5μm 的范围。CFD 结果与体外预测的偏差在 10%以内，并突出了液滴逐渐稳定的尺寸增加，这将有效减少胸外沉积并产生深呼吸道内的沉积。
增强赋形剂生长（EEG）似乎提供了一种有效增加药物气溶胶尺寸的技术，而开发的 CFD 模型将为优化该技术以产生高效肺输送提供强大的设计工具。
