Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, 401 West Main Street, P.O. Box 843015, Richmond, Virginia, 23284-3015 , USA.
Department of Pharmaceutics, Virginia Commonwealth University, Richmond, Virginia, USA.
Pharm Res. 2023 May;40(5):1193-1207. doi: 10.1007/s11095-022-03316-9. Epub 2022 Jun 27.
This study evaluated the in vitro aerosol performance of a dry powder antibiotic product that combined a highly dispersible tobramycin powder with a previously optimized pediatric air-jet dry powder inhaler (DPI) across a subject age range of 2-10 years.
An excipient enhanced growth (EEG) formulation of the antibiotic tobramycin (Tobi) was prepared using a small particle spray drying technique that included mannitol as the hygroscopic excipient and trileucine as the dispersion enhancer. The Tobi-EEG formulation was aerosolized using a positive-pressure pediatric air-jet DPI that included a 3D rod array. Realistic in vitro experiments were conducted in representative airway models consistent with children in the age ranges of 2-3, 5-6 and 9-10 years using oral or nose-to-lung administration, non-humidified or humidified airway conditions, and constant or age-specific air volumes.
Across all conditions tested, mouth-throat depositional loss was < 1% and nose-throat depositional loss was < 3% of loaded dose. Lung delivery efficiency was in the range of 77.3-85.1% of loaded dose with minor variations based on subject age (~ 8% absolute difference), oral or nasal administration (< 2%), and delivered air volume (< 2%). Humidified airway conditions had an insignificant impact on extrathoracic depositional loss and significantly increased aerosol size at the exit of a representative lung chamber.
In conclusion, the inhaled antibiotic product nearly eliminated extrathoracic depositional loss, demonstrated high efficiency nose-to-lung antibiotic aerosol delivery in pediatric airway models for the first time, and provided ~ 80% lung delivery efficiency with little variability across subject age and administered air volume.
本研究评估了一种干粉抗生素产品的体外气溶胶性能，该产品将高度可分散的妥布霉素粉末与之前优化的儿科空气射流干粉吸入器（DPI）结合使用，涵盖了 2-10 岁的受试者年龄范围。
使用包括甘露醇作为吸湿剂和三亮氨酸作为分散增强剂的小颗粒喷雾干燥技术，制备抗生素妥布霉素（Tobi）的赋形剂增强生长（EEG）制剂。使用包括 3D 棒阵列的正压儿科空气射流 DPI 使 Tobi-EEG 制剂气溶胶化。使用符合 2-3 岁、5-6 岁和 9-10 岁儿童的代表性气道模型进行了现实的体外实验，使用口服或鼻-肺给药、非加湿或加湿气道条件以及恒定或特定年龄的空气量。
在所有测试条件下，口腔-咽喉沉积损失均<加载剂量的 1%，鼻-咽喉沉积损失均<加载剂量的 3%。肺部输送效率在加载剂量的 77.3-85.1%范围内，基于受试者年龄（~8%的绝对差异）、口服或鼻内给药（<2%）和输送空气量（<2%）略有变化。加湿气道条件对胸外沉积损失的影响不大，但显著增加了代表性肺室出口处的气溶胶尺寸。
总之，吸入抗生素产品几乎消除了胸外沉积损失，首次在儿科气道模型中证明了高效的鼻-肺抗生素气溶胶输送，并提供了~80%的肺部输送效率，在受试者年龄和输送空气量方面变化很小。
