Barry P W, O'Callaghan C
Department of Child Health, University of Leicester, Leicester, United Kingdom.
J Allergy Clin Immunol. 1999 Dec;104(6):1205-10. doi: 10.1016/s0091-6749(99)70014-x.
Spacer devices are increasingly used to aid inhalational therapy, and many different devices are available. Patient and spacer size and spacer static charge may affect drug delivery, but the optimum spacer size and method of reducing static charge is not certain.
We sought to determine the output of budesonide from 3 different spacer devices when assessed by using simulated breathing at different tidal volumes and to assess the effect of washing and handling the spacer on drug output.
Three spacer types were assessed: 2 polycarbonate spacers, the Aerochamber and the Nebuhaler, and the metal Nebuchamber or Non-Electrostatic-Spacer. Breathing was simulated by using a sinus flow pump. Metered-dose inhalers of budesonide 200 microg were actuated into the spacer, which was attached to the breathing simulator for 5 simulated breathing cycles. Budesonide was collected on a filter placed between the spacer and breathing simulator and was assayed by HPLC. Spacers were assessed after they had been washed briefly in water, after they had been washed briefly in cetrimide solution in an attempt to reduce their static charge, and after they had been handled to simulate normal use. In separate experiments budesonide particle size from the spacers was measured by using a multistage liquid impinger.
Drug output from the Nebuchamber was greater than that from the other 2 spacers, especially at lower tidal volumes. With 150 mL of tidal volume, the Nebuchamber delivered 36% of the nominal dose to the filter versus 13% from the Nebuhaler and 7% from the Aerochamber. The output from the Aerochamber and Nebuhaler increased linearly with tidal volume, but this was not the case with the Nebuchamber, in which output was constant at tidal volumes of 150 mL and above. Compared with washing in tap water, neither washing the spacers in 0.1% cetrimide solution nor vigorous wiping with a paper towel changed their output. Thirty-eight percent of the drug from the Nebuchamber was contained in particles smaller than 4.7 microm in diameter compared with 47% from the Nebuhaler and 53% from the Aerochamber.
The Nebuchamber increases in vitro budesonide delivery compared with the polycarbonate spacers tested but delivers a greater percentage of the drug in large particles. No increase in delivery with tidal volume was seen with the Nebuchamber, which would deliver a higher dose of drug per kilogram of body weight to smaller patients. Briefly washing the polycarbonate spacers in water or in a weak detergent solution, simulating household washing, did not make them as effective as the metal spacer. Further research is needed to determine a practical washing and handling method to reduce static charge on polycarbonate spacers.
储雾罐装置越来越多地用于辅助吸入治疗，市面上有许多不同的装置可供选择。患者和储雾罐的尺寸以及储雾罐的静电荷可能会影响药物递送，但最佳的储雾罐尺寸和减少静电荷的方法尚不确定。
我们试图通过在不同潮气量下模拟呼吸来测定布地奈德从3种不同储雾罐装置中的输出量，并评估清洗和操作储雾罐对药物输出的影响。
评估了3种储雾罐类型：2种聚碳酸酯储雾罐，即爱全乐储雾罐（Aerochamber）和碟式吸入器储雾罐（Nebuhaler），以及金属的碟式吸入器储雾罐（Nebuchamber）或非静电储雾罐（Non-Electrostatic-Spacer）。使用正弦流泵模拟呼吸。将200微克布地奈德的定量吸入器喷入储雾罐，该储雾罐连接到呼吸模拟器进行5个模拟呼吸周期。布地奈德收集在置于储雾罐和呼吸模拟器之间的滤器上，并通过高效液相色谱法进行测定。储雾罐在水中短暂冲洗后、在西曲溴铵溶液中短暂冲洗以试图减少其静电荷后以及在模拟正常使用进行操作后进行评估。在单独的实验中，使用多级液体冲击器测量储雾罐中布地奈德的粒径。
碟式吸入器储雾罐（Nebuchamber）的药物输出量大于其他2种储雾罐，尤其是在较低潮气量时。潮气量为150毫升时，碟式吸入器储雾罐（Nebuchamber）将36%的标称剂量递送至滤器，而碟式吸入器储雾罐（Nebuhaler）为13%，爱全乐储雾罐（Aerochamber）为7%。爱全乐储雾罐（Aerochamber）和碟式吸入器储雾罐（Nebuhaler）的输出量随潮气量呈线性增加，但碟式吸入器储雾罐（Nebuchamber）并非如此情况，其在潮气量为150毫升及以上时输出量恒定。与在自来水中冲洗相比，在0.1%西曲溴铵溶液中冲洗储雾罐或用纸巾大力擦拭均未改变其输出量。碟式吸入器储雾罐（Nebuchamber）中38%的药物包含在直径小于4.7微米的颗粒中，而碟式吸入器储雾罐（Nebuhaler）为47%，爱全乐储雾罐（Aerochamber）为53%。
与所测试的聚碳酸酯储雾罐相比，碟式吸入器储雾罐（Nebuchamber）增加了布地奈德的体外递送，但较大颗粒中的药物所占百分比更高。碟式吸入器储雾罐（Nebuchamber）未观察到随潮气量递送增加的情况，这将向较小的患者每千克体重递送更高剂量的药物。在水中或弱洗涤剂溶液中短暂冲洗聚碳酸酯储雾罐，模拟家庭清洗，并未使其与金属储雾罐一样有效。需要进一步研究以确定一种实用的清洗和操作方法来减少聚碳酸酯储雾罐上的静电荷。
