背景:COPD患者的个性化治疗需要适当选择药物和递送装置。吸入器和雾化器的药物输送特性各不相同,特别是需要被动或主动吸入患者以进行适当的药物分散和递送。在这个体外分析中,我们评估了两种长效毒蕈碱拮抗剂的气溶胶性能和药物递送,格隆溴铵(GLY;25µg溶液;1ml)和噻托铵(TIO;18µg粉末)通过各自的输送系统:eFlow®封闭系统(CS)振动膜雾化器和HandiHaler®干粉吸入器(DPI)。
方法:使用下一代级联冲击器测定eFlow®CS雾化器和HandiHaler®的气溶胶性能。使用不同的呼吸模式确定GLY和TIO的递送剂量,潮气量和峰值吸气流速不同,分别,模拟从正常到严重阻塞的呼吸条件。
结果:空气动力学颗粒分析显示质量中值空气动力学直径大致相似(MMAD,范围,3.6-4.6µm)和细颗粒分数(FPF,范围,48.2%-63.7%),在所有测试的呼吸模式下,使用eFlow®CS雾化器输送GLY。TIO,通过HandiHaler®交付,显示MMAD的变化(范围,3.8-5.8µm)和FPF(范围,16.1%-32.4%)在不同吸气流速下。GLY的大部分沉积在撞击器的第2-5级,与可吸入范围内的颗粒尺寸(<5µm)相对应,而大部分TIO沉积在喉部/烟嘴预分离器中,无论测试条件如何。与使用HandiHaler®的TIO相比,使用eFlow®CS的GLY的中位残留剂量明显更低(2.4%-4.4%vs.40%-67%,分别)。
结论:这些模拟结果突出了DPI设备和振动膜雾化器产生的不同沉积模式,这可能有助于在COPD管理中告知设备选择和治疗决策。
BACKGROUND: Personalized therapy for patients with COPD requires appropriate choice of drug and delivery device. Inhalers and nebulizers vary in their drug delivery characteristics, particularly the need for passive or active patient inhalation for appropriate drug dispersal and delivery. In this in vitro analysis, we assessed the aerosol performance and drug delivery of two long-acting muscarinic antagonists, glycopyrrolate (GLY; 25 µg solution; 1 ml) and tiotropium (TIO; 18 µg powder) through their respective delivery systems: the eFlow® Closed System (CS) vibrating membrane nebulizer and the HandiHaler® dry-powder inhaler (DPI).
METHODS: The aerosol performances of the eFlow® CS nebulizer and the HandiHaler® were determined using the Next Generation cascade Impactor. The delivered dose of GLY and TIO was determined using different breathing patterns, which varied in tidal volume and peak inspiratory flow rate, respectively, to simulate breathing conditions ranging from normal to severe obstruction.
RESULTS: Aerodynamic particle analysis showed generally similar mass median aerodynamic diameter (MMAD, range, 3.6-4.6 µm) and fine particle fraction (FPF, range, 48.2%-63.7%) with GLY delivered using the eFlow® CS nebulizer under all breathing patterns tested. TIO, delivered via the HandiHaler®, showed variations in MMAD (range, 3.8-5.8 µm) and FPF (range, 16.1%-32.4%) under different inspiratory flow rates. The majority of GLY was deposited in stages 2-5 of the impactor, which corresponds with particle sizes in the respirable range (< 5 µm), whereas a large proportion of TIO was deposited in the throat/mouthpiece pre-separator, irrespective of test conditions. The median residual dose of GLY with eFlow® CS was notably lower compared to that of TIO with HandiHaler® (2.4%-4.4% vs. 40%-67%, respectively).
CONCLUSIONS: These simulation results highlight the different deposition patterns generated by a DPI device and a vibrating membrane nebulizer, which may help inform device selection and treatment decision in COPD management.