Young Paul M, Crapper John, Philips Gary, Sharma Ketan, Chan Hak-Kim, Traini Daniela
1 Respiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology, Sydney Medical School, The University of Sydney , NSW 2037, Australia .
J Aerosol Med Pulm Drug Deliv. 2014 Apr;27(2):138-47. doi: 10.1089/jamp.2013.1080. Epub 2013 Sep 4.
A new approach to delivering high doses of dry powder medicaments to the lung is presented. The Orbital(®) dry powder device is designed to deliver high doses of drugs to the respiratory tract in a single dosing unit, via multiple inhalation maneuvers, overcoming the need to prime or insert multiple capsules.
The Orbital was tested in its prototype configuration and compared with a conventional RS01 capsule device. Three formulations were evaluated: 200 mg of spray-dried ciprofloxacin formulation for respiratory infection, 200 mg of spray-dried mannitol formulation for mucus clearance, and 100, 200, and 400 mg of co-spray-dried 1:8 formulations containing ciprofloxacin and mannitol as combination therapy. The systems were evaluated in terms of physicochemical properties and tested using a multistage liquid impinger at 60 L/min. Emptying rates were evaluated, and the aerosolization performance compared with 10 capsules used sequentially in the RS01.
The systems were different in terms of morphology, thermal response, moisture sorption, and stability; however, they had similar sizes when measured by laser diffraction, making them suitable for comparison in the Orbital and RS01 devices. The aerosolization performance from the Orbital device and RS01 was dependent on the formulation type; however, the fine particle fraction (FPF) produced by the Orbital device was higher than that by the RS01. The FPFs for ciprofloxacin, mannitol, and co-spray-dried formulation were 67.1±1.8, 47.1±2.2, and 42.0±1.8, respectively. For the Orbital, 90% of the loaded dose was delivered within 10 inhalation maneuvers, with the profile being dependent on the formulation type.
The Orbital provides a means of delivering high doses of medicine to the respiratory tract through multiple breath maneuvers after a single actuation. This approach will allow the delivery of a wide range of high-payload formulations (>100 mg) for the treatment of a variety of lung disorders. To date, no such passive device exists that meets these crucial criteria.
介绍一种向肺部输送高剂量干粉药物的新方法。Orbital（®）干粉装置旨在通过多次吸入动作，在单个给药单元中将高剂量药物输送到呼吸道，无需预充或插入多个胶囊。
对Orbital的原型配置进行测试，并与传统的RS01胶囊装置进行比较。评估了三种制剂：用于呼吸道感染的200毫克喷雾干燥环丙沙星制剂、用于黏液清除的200毫克喷雾干燥甘露醇制剂，以及100、200和400毫克含环丙沙星和甘露醇的共喷雾干燥1:8制剂作为联合治疗。从物理化学性质方面对这些系统进行评估，并使用多级液体撞击器以60升/分钟的速度进行测试。评估排空率，并将雾化性能与在RS01中依次使用的10个胶囊进行比较。
这些系统在形态、热响应、吸湿和稳定性方面存在差异；然而，通过激光衍射测量时它们的尺寸相似，这使得它们适合在Orbital和RS01装置中进行比较。Orbital装置和RS01的雾化性能取决于制剂类型；然而，Orbital装置产生的细颗粒分数（FPF）高于RS01。环丙沙星、甘露醇和共喷雾干燥制剂的FPF分别为67.1±1.8、47.1±2.2和42.0±1.8。对于Orbital，90%的加载剂量在10次吸入动作内输送完毕，其分布情况取决于制剂类型。
Orbital提供了一种在单次启动后通过多次呼吸动作向呼吸道输送高剂量药物的方法。这种方法将允许输送各种高载量制剂（>100毫克）用于治疗多种肺部疾病。迄今为止，不存在满足这些关键标准的此类被动装置。
