Kimbell Julia S, Segal Rebecca A, Asgharian Bahman, Wong Brian A, Schroeter Jeffry D, Southall Jeremy P, Dickens Colin J, Brace Geoff, Miller Frederick J
The Hamner Institutes for Health Sciences.
J Aerosol Med. 2007 Spring;20(1):59-74. doi: 10.1089/jam.2006.0531.
Many studies suggest limited effectiveness of spray devices for nasal drug delivery due primarily to high deposition and clearance at the front of the nose. Here, nasal spray behavior was studied using experimental measurements and a computational fluid dynamics model of the human nasal passages constructed from magnetic resonance imaging scans of a healthy adult male. Eighteen commercially available nasal sprays were analyzed for spray characteristics using laser diffraction, high-speed video, and high-speed spark photography. Steadystate, inspiratory airflow (15 L/min) and particle transport were simulated under measured spray conditions. Simulated deposition efficiency and spray behavior were consistent with previous experimental studies, two of which used nasal replica molds based on this nasal geometry. Deposition fractions (numbers of deposited particles divided by the number released) of 20- and 50-microm particles exceeded 90% in the anterior part of the nose for most simulated conditions. Predicted particle penetration past the nasal valve improved when (1) the smaller of two particle sizes or the lower of two spray velocities was used, (2) the simulated nozzle was positioned 1.0 rather than 0.5 or 1.5 cm into the nostril, and (3) inspiratory airflow was present rather than absent. Simulations also predicted that delaying the appearance of normal inspiratory airflow more than 1 sec after the release of particles produced results equivalent to cases in which no inspiratory airflow was present. These predictions contribute to more effective design of drug delivery devices through a better understanding of the effects of nasal airflow and spray characteristics on particle transport in the nose.
许多研究表明,喷雾装置用于鼻腔给药的效果有限,主要原因是药物在前鼻处的高沉积和清除率。在此,利用实验测量和基于一名健康成年男性磁共振成像扫描构建的人类鼻腔通道计算流体动力学模型,对鼻腔喷雾行为进行了研究。使用激光衍射、高速视频和高速火花摄影对18种市售鼻腔喷雾剂的喷雾特性进行了分析。在测量的喷雾条件下模拟了稳态吸气气流(15升/分钟)和颗粒传输。模拟的沉积效率和喷雾行为与先前的实验研究一致,其中两项研究使用了基于这种鼻腔几何形状的鼻腔复制模具。在大多数模拟条件下,20微米和50微米颗粒在前鼻处的沉积分数(沉积颗粒数除以释放颗粒数)超过90%。当使用以下条件时,预测的颗粒通过鼻瓣的穿透性会提高:(1)两种颗粒尺寸中较小的尺寸或两种喷雾速度中较低的速度;(2)模拟喷嘴位于鼻孔内1.0厘米而非0.5厘米或1.5厘米处;(3)存在吸气气流而非无气流。模拟还预测,在颗粒释放后延迟正常吸气气流出现超过1秒所产生的结果与无吸气气流的情况相当。这些预测有助于通过更好地理解鼻腔气流和喷雾特性对鼻腔内颗粒传输的影响,更有效地设计给药装置。