Longest P Worth, Golshahi Laleh, Behara Srinivas R B, Tian Geng, Farkas Dale R, Hindle Michael
1Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, Virginia.
2Department of Pharmaceutics, Virginia Commonwealth University, Richmond, Virginia.
J Aerosol Med Pulm Drug Deliv. 2015 Jun;28(3):189-201. doi: 10.1089/jamp.2014.1158. Epub 2014 Sep 5.
Delivering aerosols to the lungs through the nasal route has a number of advantages, but its use has been limited by high depositional loss in the extrathoracic airways. The objective of this study was to evaluate the nose-to-lung (N2L) delivery of excipient enhanced growth (EEG) formulation aerosols generated with a new inline dry powder inhaler (DPI). The device was also adapted to enable aerosol delivery to a patient simultaneously receiving respiratory support from high flow nasal cannula (HFNC) therapy.
The inhaler delivered the antibiotic ciprofloxacin, which was formulated as submicrometer combination particles containing a hygroscopic excipient prepared by spray-drying. Nose-to-lung delivery was assessed using in vitro and computational fluid dynamics (CFD) methods in an airway model that continued through the upper tracheobronchial region.
The best performing device contained a 2.3 mm flow control orifice and a 3D rod array with a 3-4-3 rod pattern. Based on in vitro experiments, the emitted dose from the streamlined nasal cannula had a fine particle fraction <5 μm of 95.9% and mass median aerodynamic diameter of 1.4 μm, which was considered ideal for nose-to-lung EEG delivery. With the 2.3-343 device, condensational growth in the airways increased the aerosol size to 2.5-2.7 μm and extrathoracic deposition was <10%. CFD results closely matched the in vitro experiments and predicted that nasal deposition was <2%.
The developed DPI produced high efficiency aerosolization with significant size increase of the aerosol within the airways that can be used to enable nose-to-lung delivery and aerosol administration during HFNC therapy.
通过鼻腔途径将气溶胶输送到肺部有诸多优点，但其应用受到胸外气道中高沉积损失的限制。本研究的目的是评估使用新型在线干粉吸入器（DPI）产生的赋形剂增强生长（EEG）制剂气溶胶的鼻至肺（N2L）输送。该装置还进行了改进，以实现向同时接受高流量鼻导管（HFNC）治疗的呼吸支持的患者输送气溶胶。
吸入器输送抗生素环丙沙星，其被配制成含有通过喷雾干燥制备的吸湿赋形剂的亚微米级复合颗粒。在延伸至上气管支气管区域的气道模型中，使用体外和计算流体动力学（CFD）方法评估鼻至肺输送。
性能最佳的装置包含一个2.3毫米的流量控制孔和一个具有3-4-3杆图案的三维杆阵列。基于体外实验，流线型鼻导管的发射剂量中粒径<5μm的细颗粒分数为95.9%，质量中位空气动力学直径为1.4μm，这被认为是鼻至肺EEG输送的理想值。使用2.3-343装置时，气道中的凝结生长将气溶胶尺寸增加到2.5-2.7μm，胸外沉积<10%。CFD结果与体外实验密切匹配，并预测鼻腔沉积<2%。
所开发的DPI产生了高效雾化，气道内气溶胶尺寸显著增加，可用于在HFNC治疗期间实现鼻至肺输送和气溶胶给药。
