1 Sunovion Pharmaceuticals, Inc. , Marlborough, Massachusetts.
2 Pulmonary Research Institute of Southeast Michigan , Farmington Hills, Michigan.
J Aerosol Med Pulm Drug Deliv. 2018 Jun;31(3):162-169. doi: 10.1089/jamp.2017.1384. Epub 2017 Nov 10.
Glycopyrrolate administered by a novel, investigational eFlow Closed System (CS) nebulizer (eFlow CS) is being evaluated for the maintenance treatment of chronic obstructive pulmonary disease (COPD). The eFlow CS is a hand-held, vibrating membrane nebulizer optimized to deliver 1 mL of glycopyrrolate solution into the lung in <3 minutes. Clinical studies have shown improvements in lung function of subjects treated with nebulized glycopyrrolate.
The aerosol performance of the eFlow CS nebulizer was characterized by delivered dose, aerodynamic droplet size distribution and nebulization time. Simulated use nebulizer performance over 60 days was assessed by volume median diameter (VMD), nebulized amount, and nebulization time. Nebulization outputs were assayed to ensure adequate delivery of glycopyrrolate with an acceptable impurity profile. Aerosol condensates were analyzed for glycopyrrolate concentration and impurities by ultra-high-performance liquid chromatography and compared with non-nebulized samples.
The mean mass median aerodynamic diameter, geometric standard deviation, and fine particle fraction were 3.7 μm, 1.7, and 72%, respectively, and independent of formulation strength (25 and 50 μg/mL). Delivered dose was 88% of the nominal dose for both formulation strengths. The mean delivered dose, assessed by breathing simulation, was 56.8% for 25 μg/mL and 62.6% for 50 μg/mL. Nebulization times were 1-2.5 minutes with no apparent increasing trend with use over a 60-day period. The nebulized amount showed no significant changes, whereas the VMD showed a slight, but not pharmaceutically relevant, increase (0.1-0.2 μm) after 60-day simulated use. Glycopyrrolate concentration and impurity levels of nebulized samples were statistically similar to those of non-nebulized samples.
The eFlow CS generates glycopyrrolate aerosols with high delivered dose, short treatment time, and small droplet size with narrow size distribution suitable for central and peripheral airway deposition. The unit dose vial mitigates medication misuse and ensures dose uniformity. Results support the use of glycopyrrolate/eFlow CS for the treatment of COPD.
正在评估新型、研究性的 eFlow 密闭系统（CS）雾化器（eFlow CS）给药的硫酸 格隆溴铵用于慢性阻塞性肺疾病（COPD）的维持治疗。eFlow CS 是一种手持式、振动膜雾化器，优化后可在 <3 分钟内将 1 毫升硫酸格隆溴铵溶液递送至肺部。临床研究表明，接受雾化硫酸格隆溴铵治疗的受试者的肺功能得到改善。
通过递送至剂量、空气动力学雾滴粒径分布和雾化时间来描述 eFlow CS 雾化器的气溶胶性能。通过体积中值直径（VMD）、雾化量和雾化时间评估模拟使用 60 天的雾化器性能。对雾化输出物进行检测，以确保硫酸格隆溴铵的输送量充足，杂质谱可接受。通过超高效液相色谱法对气溶胶冷凝物中的硫酸格隆溴铵浓度和杂质进行分析，并与非雾化样品进行比较。
平均质量中值空气动力学直径、几何标准差和细颗粒分数分别为 3.7μm、1.7 和 72%，且与制剂强度（25 和 50μg/mL）无关。两种制剂强度的递送至剂量均为名义剂量的 88%。通过呼吸模拟评估的平均递送至剂量，25μg/mL 为 56.8%，50μg/mL 为 62.6%。雾化时间为 1-2.5 分钟，在 60 天的模拟使用过程中，无明显的使用时间增加趋势。雾化量无明显变化，而 VMD 在 60 天模拟使用后略有增加（0.1-0.2μm），但无药相关意义。雾化样品的硫酸格隆溴铵浓度和杂质水平与非雾化样品统计学相似。
eFlow CS 产生的硫酸格隆溴铵气溶胶具有高递送至剂量、短治疗时间、小雾滴尺寸和窄粒径分布，适合中央和外周气道沉积。单位剂量小瓶可减少用药不当并确保剂量均匀性。结果支持使用硫酸格隆溴铵/eFlow CS 治疗 COPD。
