Golshahi Laleh, Longest P Worth, Azimi Mandana, Syed Aamer, Hindle Michael
Department of Pharmaceutics.
Department of Pharmaceutics Department of Mechanical and Nuclear Engineering.
Respir Care. 2014 Oct;59(10):1476-86. doi: 10.4187/respcare.02903. Epub 2014 Jun 10.
Use of submicrometer particles combined with condensational growth techniques has been proposed to reduce drug losses within components of high-flow nasal cannula therapy systems and to enhance the dose reaching the lower respiratory tract. These methods have been evaluated using continuous inhalation flow rather than realistic inhalation/exhalation breathing cycles. The goal of this study was to evaluate in vitro aerosol drug delivery using condensational growth techniques during high-flow nasal cannula therapy using realistic breathing profiles and incorporating intermittent aerosol delivery techniques.
A mixer-heater combined with a vibrating mesh nebulizer was used to generate a submicrometer aerosol using a formulation of 0.2% albuterol sulfate and 0.2% sodium chloride in water. Delivery efficiency of the aerosol for 1 min through a nasal cannula was considered using an intermittent delivery regime with aerosol being emitted for either the entire inhalation time (2 s) or half of the inhalation period (1 s) and compared with continuous delivery. The deposition of the aerosol was evaluated in the nasal delivery components (ventilator tubing and cannula) and an in vitro adult nose-mouth-throat (NMT) model using 3 realistic breathing profiles.
Significant improvements in dose delivered to the exit of the NMT model (ex-NMT) were observed for both condensational growth methods using intermittent aerosol delivery compared with continuous delivery, and increasing the tidal volume was found useful. The combination of the largest tidal volume with the shortest intermittent delivery time resulted in the lowest respiration losses and the highest ex-NMT delivered dose.
Intermittent aerosol delivery using realistic breathing profiles of submicrometer condensational growth aerosols was found to be efficient in delivering nasally administered drugs in an in vitro airway model.
有人提出使用亚微米颗粒结合凝结生长技术,以减少高流量鼻导管治疗系统组件内的药物损失,并提高到达下呼吸道的剂量。这些方法已通过持续吸入气流而非实际的吸入/呼出呼吸周期进行评估。本研究的目的是在高流量鼻导管治疗期间,使用实际呼吸曲线并结合间歇性气溶胶输送技术,评估凝结生长技术的体外气溶胶药物递送情况。
使用混合加热器与振动网式雾化器相结合,以水中0.2%硫酸沙丁胺醇和0.2%氯化钠的配方生成亚微米气溶胶。通过鼻导管进行1分钟的气溶胶递送效率,采用间歇性递送方案进行评估,气溶胶在整个吸气时间(2秒)或吸气期的一半(1秒)内喷出,并与持续递送进行比较。使用3种实际呼吸曲线,在鼻递送组件(呼吸机管路和鼻导管)和体外成人鼻-口-喉(NMT)模型中评估气溶胶的沉积情况。
与持续递送相比,使用间歇性气溶胶递送的两种凝结生长方法在递送至NMT模型出口(ex-NMT)的剂量方面均有显著改善,并且发现增加潮气量是有用的。最大潮气量与最短间歇性递送时间的组合导致呼吸损失最低,ex-NMT递送剂量最高。
在体外气道模型中,使用亚微米凝结生长气溶胶的实际呼吸曲线进行间歇性气溶胶递送,被发现能有效地递送经鼻给药的药物。