Development of CPAP Overlay Interfaces for Efficient Administration of Aerosol Surfactant Therapy to Preterm Infants

IF 3.4 4区 医学 Q2 PHARMACOLOGY & PHARMACY AAPS PharmSciTech Pub Date : 2025-01-16 DOI:10.1208/s12249-024-02987-4
Hasan Jubaer, Sarah Strickler, Dale Farkas, Caleb Dalton, Mohammad A. M. Momin, Kelley M. Dodson, Michael Hindle, Worth Longest
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Abstract

The administration of surfactant aerosol therapy to preterm infants receiving continuous positive airway pressure (CPAP) respiratory support is highly challenging due to small flow passages, relatively high ventilation flow rates, rapid breathing and small inhalation volumes. To overcome these challenges, the objective of this study was to implement a validated computational fluid dynamics (CFD) model and develop an overlay nasal prong interface design for use with CPAP respiratory support that enables high efficiency powder aerosol delivery to the lungs of preterm infants when needed (i.e., on-demand) and can remain in place without increasing the work of breathing compared with a baseline CPAP interface. Realistic in vitro experiments were first conducted to generate baseline validation data, and then the CFD model, once validated, was used to explore key design parameters across a range of preterm infant nose-throat geometries and aerosol delivery conditions. The most important factors for efficient aerosol delivery were shown to be (i) maintaining the aerosol delivery flow rate below the tracheal flow rate (to minimize CPAP line loss) and (ii) concentrating the aerosol within the first portion of the inhalation waveform. An optimized design was shown to deliver approximately 37–60% of the nominal dose through the system and to the lungs with low intersubject variability (1050–2200 g infants) across two modes of device actuation (automated and manual) with room for further improvement. Ergonomic curvatures and streamlining of the prong geometries were also found to reduce work of breathing and flow resistance compared with a commercial alternative.

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用于早产儿气溶胶表面活性剂有效给药的CPAP覆盖界面的开发
对于接受持续气道正压通气(CPAP)呼吸支持的早产儿,表面活性剂气雾剂治疗具有很高的挑战性,因为其气道小,通气流速相对较高,呼吸急促,吸入量小。为了克服这些挑战,本研究的目的是实施一个经过验证的计算流体动力学(CFD)模型,并开发一种覆盖鼻尖接口设计,用于CPAP呼吸支持,能够在需要时(即按需)高效地将粉末气溶胶输送到早产儿的肺部,并且与基线CPAP接口相比,可以保持在适当的位置,而不会增加呼吸工作。首先进行实际的体外实验以生成基线验证数据,然后使用CFD模型,一旦验证,用于探索一系列早产儿鼻-喉几何形状和气溶胶输送条件的关键设计参数。有效气溶胶输送的最重要因素被证明是(i)保持气溶胶输送流速低于气管流速(以尽量减少CPAP线路损耗)和(ii)将气溶胶集中在吸入波形的第一部分。优化设计表明,通过两种装置驱动模式(自动和手动),通过系统和肺部提供约37-60%的标称剂量,受试者间可变性低(1050-2200 g婴儿),并有进一步改进的空间。与商业替代品相比,符合人体工程学的曲率和尖头几何形状的流线型也减少了呼吸和流动阻力的工作。图形抽象
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来源期刊
AAPS PharmSciTech
AAPS PharmSciTech 医学-药学
CiteScore
6.80
自引率
3.00%
发文量
264
审稿时长
2.4 months
期刊介绍: AAPS PharmSciTech is a peer-reviewed, online-only journal committed to serving those pharmaceutical scientists and engineers interested in the research, development, and evaluation of pharmaceutical dosage forms and delivery systems, including drugs derived from biotechnology and the manufacturing science pertaining to the commercialization of such dosage forms. Because of its electronic nature, AAPS PharmSciTech aspires to utilize evolving electronic technology to enable faster and diverse mechanisms of information delivery to its readership. Submission of uninvited expert reviews and research articles are welcomed.
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