Department of Pharmaceutics, Virginia Commonwealth University, 410 N 12th St., Box 980533, Richmond, Virginia, USA,
Pharm Res. 2013 Nov;30(11):2917-30. doi: 10.1007/s11095-013-1123-3. Epub 2013 Jun 26.
The objective of this study was to evaluate the delivery of nasally administered aerosols to the lungs during noninvasive ventilation using controlled condensational growth techniques.
An optimized mixer, combined with a mesh nebulizer, was used to generate submicrometer aerosol particles using drug alone (albuterol sulfate) and with mannitol or sodium chloride added as hygroscopic excipients. The deposition and growth of these particles were evaluated in an adult nose-mouth-throat (NMT) model using in vitro experimental methods and computational fluid dynamics simulations.
Significant improvement in the lung dose (3-4× increase) was observed using excipient enhanced growth (EEG) and enhanced condensational growth (ECG) delivery modes compared to control studies performed with a conventional size aerosol (~5 μm). This was due to reduced device retention and minimal deposition in the NMT airways. Increased condensational growth of the initially submicrometer particles was observed using the ECG mode and in the presence of hygroscopic excipients. CFD predictions for regional drug deposition and aerosol size increase were in good agreement with the observed experimental results.
These controlled condensational growth techniques for the delivery of submicrometer aerosols were found to be highly efficient methods for delivering nasally-administered drugs to the lungs.
本研究旨在评估使用控制冷凝生长技术在无创通气期间将鼻腔内给予的气雾剂输送到肺部。
采用优化的混合器与网式雾化器结合,使用单独的药物(硫酸沙丁胺醇)以及添加作为吸湿赋形剂的甘露醇或氯化钠来生成亚微米气溶胶颗粒。使用体外实验方法和计算流体动力学模拟在成人口鼻咽喉(NMT)模型中评估这些颗粒的沉积和生长。
与使用传统大小气溶胶(~5μm)进行的对照研究相比,使用赋形剂增强生长(EEG)和增强冷凝生长(ECG)输送模式,观察到肺剂量(增加 3-4 倍)显著改善。这是由于装置保留减少和 NMT 气道中的沉积最小化。使用 ECG 模式和存在吸湿赋形剂时,观察到初始亚微米颗粒的增加冷凝生长。CFD 预测的区域药物沉积和气溶胶尺寸增加与观察到的实验结果非常吻合。
这些用于输送亚微米气溶胶的控制冷凝生长技术被发现是将鼻内给予的药物高效输送到肺部的方法。