In Vitro Dosing Performance of the ELLIPTA® Dry Powder Inhaler Using Asthma and COPD Patient Inhalation Profiles Replicated with the Electronic Lung (eLung™).
In Vitro Dosing Performance of the ELLIPTA® Dry Powder Inhaler Using Asthma and COPD Patient Inhalation Profiles Replicated with the Electronic Lung (eLung™).
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DOI：
10.1089/jamp.2015.1225
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发表时间：
2015-12
影响因子：
3.4
通讯作者：
Prime D
中科院分区：
文献类型：
--
作者：
Hamilton M;Leggett R;Pang C;Charles S;Gillett B;Prime D
背景：为了评估经批准的哮喘和慢性阻塞性肺疾病（COPD）疗法通过ELLIPTA®干粉吸入器在代表目标患者群体的吸入终点上的体外剂量传递特性，使用电子肺（eLung™）复制先前在体内记录的吸入器特异性患者吸入谱。方法：选定的代表所有严重哮喘和COPD患者达到的吸入终点范围的概况，使用eLung呼吸模拟器和口咽铸型进行复制。将下一代冲击器连接到eLung上，以确定通过ELLIPTA吸入器输送的哮喘和COPD治疗的喉前剂量（ETD）的空气动力学粒径分布。测定糠酸氟替卡松(FF)/维兰特罗（VI） 100/25 μg和200/25 μg（哮喘和COPD）、乌莫替尼(UMEC)/VI 62.5/25 μg （COPD）、FF 100 μg和200μg单药（哮喘）和UMEC 62.5 μg单药（COPD）的递送剂量（DD）、ETD和细颗粒剂量（FPD，定义为活性物质质量小于5 μm）。结果：eLung复制的吸入谱覆盖了较大范围的峰值吸入流量（41.6 ~ 136.9 L/min）、压降（1.2 ~ 13.8 kPa）和吸入量（0.7 ~ 4.2L）。DD在评估的每种治疗的所有成分（FF、VI和UMEC）的患者代表性吸入参数范围内是一致的；虽然ETD和FPD也基本一致，但观察到一些小的变化。无论是单独给药还是联合给药，每种成分的给药剂量都是一致的。结论：ELLIPTA吸入器的体外性能已被证明可用于FF/VI、UMEC/VI、FF单药治疗和UMEC单药治疗。在整个吸气剖面范围内，DD是一致的，而ETD和FPD几乎没有流量依赖性。
Background: To evaluate the in vitro dose delivery characteristics of approved asthma and chronic obstructive pulmonary disease (COPD) therapies delivered via the ELLIPTA® dry powder inhaler across inhalation endpoints representative of the target patient population, using the Electronic Lung (eLung™) to replicate inhaler-specific patient inhalation profiles that were previously recorded in vivo. Methods: Selected profiles, representative of the range of inhalation endpoints achieved by patients with all severities of asthma and COPD, were replicated using the eLung breathing simulator in conjunction with an oropharyngeal cast. A Next Generation Impactor was coupled to the eLung to determine the aerodynamic particle size distribution of the ex-throat dose (ETD) of asthma and COPD therapies delivered via the ELLIPTA inhaler. Delivered dose (DD), ETD, and fine particle dose (FPD; defined as a mass of active substance less than 5 μm) were determined for fluticasone furoate (FF)/vilanterol (VI) 100/25 μg and 200/25 μg (asthma and COPD), umeclidinium (UMEC)/VI 62.5/25 μg (COPD only), FF 100 μg and 200μg monotherapy (asthma only), and UMEC 62.5 μg monotherapy (COPD only). Results: Inhalation profiles replicated by eLung covered a wide range of peak inspiratory flow rates (41.6–136.9 L/min), pressure drops (1.2–13.8 kPa), and inhaled volumes through the inhaler (0.7–4.2L). DD was consistent across the range of patient representative inhalation parameters for all components (FF, VI, and UMEC) of each therapy assessed; although ETD and FPD were also generally consistent, some small variation was observed. Dose delivery was consistent for each of the components, whether delivered as mono- or combination therapy. Conclusions: The in vitro performance of the ELLIPTA inhaler has been demonstrated for the delivery of FF/VI, UMEC/VI, FF monotherapy, and UMEC monotherapy. Across a range of inspiratory profiles, DD was consistent, while ETD and FPD showed little flow dependency.