氟替卡松乌美溴铵维兰特罗固定剂量复方干粉吸入剂的药物递送。
Drug Delivery of a Fixed-Dose Combination of Fluticasone Furoate/Umeclidinium/Vilanterol from a Dry Powder Inhaler.
机构信息
GSK, R&D, Ware, Hertfordshire, United Kingdom.
Karolinska Institutet, Stockholm, Sweden.
出版信息
J Aerosol Med Pulm Drug Deliv. 2023 Feb;36(1):34-43. doi: 10.1089/jamp.2021.0061. Epub 2023 Jan 25.
Dry powder inhalers (DPIs) require patients to impart sufficient energy through inhalation to ensure adequate dose emission, medication deaggregation, and resultant particle sizes suitable for lung deposition. There is an ongoing debate regarding the level of inspiratory effort, and therefore inspiratory flow rate, needed for optimal dose delivery from DPIs. The delivered dose (DD) and fine particle fraction (FPF) for each component of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 μg and FF/UMEC/VI 200/62.5/25 μg ELLIPTA DPIs were assessed at flow rates of 30, 60, and 90 L/min. Electronic lung (eLung) (eLung; an electronic breathing simulator) assessments were conducted to replicate inhalation profiles representing a wide range of inhalation parameters and inhaled volumes achieved by patients with chronic obstructive pulmonary disease (COPD) or asthma of all severity levels. Timing and duration of dose emission were assessed using a particle detector located at the entrance of an anatomical throat cast attached to the eLung. During DD assessment, a mean of >80% of the nominal blister content (nbc) was emitted from the ELLIPTA DPI at all flow rates. In Next Generation Impactor assessments, the observed mean DD across flow rates for FF/UMEC/VI 100/62.5/25 μg ranged from 85.9% to 97.0% of nbc and 84.0% to 93.5% for FF/UMEC/VI 200/62.5/25 μg. In eLung assessments, 82.8% to 95.5% of nbc was delivered across the PIF range, 43.5 to 129.9 L/min (COPD), and 85.1% to 92.3% across the PIF range, 67.4 to 129.9 L/min (asthma). The FPF (mass <5 μm; % nbc) for each component was comparable across all flow rates and inhalation profiles. Dose emission timings indicated that near-complete dose emission occurs before reaching PIF. Dose delivery assessments across all flow rates and inhalation profiles indicate that patients with all severity levels of COPD or asthma can achieve the required inspiratory effort for efficient delivery of all components of FF/UMEC/VI from the ELLIPTA DPI. Dose emission profiles suggest rapid and near-complete dose delivery from the ELLIPTA DPI before reaching PIF.
干粉吸入器(DPIs)需要患者通过吸入来施加足够的能量,以确保足够的剂量释放、药物解聚和产生适合肺部沉积的颗粒大小。对于 DPI 达到最佳剂量输送所需的吸气努力程度(因此吸气流速),目前存在持续的争论。对每个 fluticasone furoate/umeclidinium/vilanterol(FF/UMEC/VI)100/62.5/25μg 和 FF/UMEC/VI 200/62.5/25μg ELLIPTA DPIs 组件的输送剂量(DD)和细颗粒分数(FPF),在 30、60 和 90 L/min 的流速下进行了评估。使用电子肺(eLung)(电子呼吸模拟器)进行电子肺(eLung)评估,以复制代表慢性阻塞性肺疾病(COPD)或各种严重程度哮喘患者吸入参数和吸入量范围广泛的吸入特征。使用位于附着在 eLung 的解剖学喉咙铸型入口处的颗粒探测器评估剂量释放的时间和持续时间。在 DD 评估过程中,在所有流速下,ELLIPTA DPI 从每个泡罩中释放出的名义泡罩含量(nbc)的平均值均超过 80%。在下一代撞击器评估中,观察到的 FF/UMEC/VI 100/62.5/25μg 的跨流速平均 DD 范围为 nbc 的 85.9%至 97.0%,FF/UMEC/VI 200/62.5/25μg 的 84.0%至 93.5%。在 eLung 评估中,在 PIF 范围内(43.5 至 129.9 L/min,COPD),82.8%至 95.5%的 nbc 被输送,在 PIF 范围内(67.4 至 129.9 L/min,哮喘),85.1%至 92.3%被输送。每个组件的 FPF(质量 <5 μm;%nbc)在所有流速和吸入特征下均相当。剂量释放时间表明,在达到 PIF 之前,几乎可以完全释放剂量。在所有流速和吸入特征下进行的剂量输送评估表明,患有 COPD 或哮喘的所有严重程度的患者都可以达到高效输送 FF/UMEC/VI 所有组件所需的吸气努力程度。从 ELLIPTA DPI 输送的剂量发射特性表明,在达到 PIF 之前,剂量迅速且几乎完全释放。