Geller David E
Aerosol Research Laboratory and Cystic Fibrosis Center, The Nemours Children's Clinic, Orlando, FL 32806, USA.
Respir Care. 2002 Dec;47(12):1392-404; discussion 1404-5.
Over the past few decades, aerosol delivery devices have been relatively inefficient, wasteful, and difficult for patients to use. These drawbacks have been tolerated because the drugs available for inhalation have wide therapeutic margins and steep dose-response curves at low doses. Recently several forces have converged to drive innovation in the aerosol device industry: the ban on chlorofluorocarbon propellants in metered-dose inhalers, the need for more user-friendly devices, and the invention of expensive inhalable therapies for topical and systemic lung delivery. Numerous devices are in development to improve the efficiency, ease of use, and reproducibility of aerosol delivery to the lung, including systems that force liquid through a nozzle to form the aerosol cloud. The Respimat is a novel, compact, propellant-free, multi-dose inhaler that employs a spring to push drug solution through a nozzle, which generates a slow-moving aerosol. Deposition studies show that the Respimat can deliver 39-44% of a dose to the lungs. Clinical asthma and chronic obstructive pulmonary disease trials with bronchodilators show that the Respimat is 2-8 times as effective as a metered-dose inhaler. Respimat has been tested with bronchodilators and inhaled corticosteroids. The AERx device uses sophisticated electronics to deliver aerosol from a single-dose blister, using an integral, disposable nozzle array. The electronics control dose expression and titration, timing of aerosol generation with the breath, and provide feedback for proper inhalation technique. Lung deposition ranges from 50 to 80% of the loaded dose, with remarkable reproducibility. AERx has been tested with a variety of drugs, for both topical and systemic delivery, including rhDNase (dornase alfa), insulin, and opioids. These novel devices face competition from other technologies as well as financial and regulatory hurdles, but they both offer a marked improvement in the efficiency of pulmonary drug delivery.
在过去几十年中，气雾剂递送装置相对效率低下、浪费且患者使用困难。由于可供吸入的药物具有较宽的治疗窗和低剂量下陡峭的剂量反应曲线，这些缺点一直被容忍。最近，多种因素共同推动了气雾剂装置行业的创新：计量吸入器中氯氟烃推进剂的禁令、对更用户友好型装置的需求以及用于局部和全身肺部递送的昂贵可吸入疗法的发明。为提高肺部气雾剂递送的效率、易用性和可重复性，有许多装置正在研发中，包括迫使液体通过喷嘴以形成气雾剂云的系统。Respimat是一种新型、紧凑、无推进剂的多剂量吸入器，它利用弹簧推动药物溶液通过喷嘴，从而产生缓慢移动的气雾剂。沉积研究表明，Respimat可将剂量中39%至44%递送至肺部。使用支气管扩张剂进行的临床哮喘和慢性阻塞性肺疾病试验表明，Respimat的效果是计量吸入器的2至8倍。Respimat已使用支气管扩张剂和吸入性糖皮质激素进行了测试。AERx装置使用复杂的电子设备从单剂量泡罩中递送气雾剂，采用一体式一次性喷嘴阵列。电子设备控制剂量表达和滴定、气雾剂与呼吸同步产生的时间，并为正确的吸入技术提供反馈。肺部沉积量占加载剂量的50%至80%，具有显著的可重复性。AERx已使用多种药物进行了测试，用于局部和全身递送，包括重组人脱氧核糖核酸酶（多纳培南）、胰岛素和阿片类药物。这些新型装置面临来自其他技术以及财务和监管方面的障碍，但它们都在肺部药物递送效率方面有显著提高。
