Burnell Patricia K P, Asking Lars, Borgström Lars, Nichols Steve C, Olsson Bo, Prime David, Shrubb Ian
GlaxoSmithKline R&D, Ware, Herts, United Kingdom.
J Aerosol Med. 2007 Fall;20(3):269-81. doi: 10.1089/jam.2007.0566.
Magnetic resonance imaging (MRI) of the oropharyngeal region from 20 adult volunteers using four model inhalation devices (varying mouthpiece diameters, airflow resistances) and tidal breathing was carried out. Statistical analysis (convex hull method) selected 12 scans from 80 data sets representing the extremes of all dimensions in the population. Twelve physical mouth-throat models were made by stereolithography using the exact scan data. The aim was to produce models with varying dimensions to span the adult population, and to investigate if oropharyngeal dimensions affected throat retention for different delivery systems. In an in vitro analysis, the models were used to determine the retention effect of the oropharyngeal airspaces when drug aerosols were administered from four inhalation delivery systems: a pressurised metered dose inhaler (pMDI), two different dry powder inhalers (DPIs A and B), and a nebulizer. The aims of this work were to determine the key parameters governing mouth-throat retention and whether retention was dependent on the delivery system used. Characterizing the throat models by measuring 51 different dimensional variables enabled determination of the most influential variables for dose retention for each inhalation delivery system. Throat model retention was found to be dependent on the delivery system (pMDI approximately DPI(A) > DPI(B) > Neb.). The most influential variable was the total throat model volume. Throat models representing high, median, and low oropharyngeal filtration in healthy adults have been identified.
对20名成年志愿者的口咽区域进行了磁共振成像(MRI),使用四种型号的吸入装置(不同的吸嘴直径、气流阻力)并在潮式呼吸状态下进行。统计分析(凸包法)从80个数据集中选取了12次扫描,这些数据集代表了总体中所有维度的极值。利用精确的扫描数据通过立体光刻制作了12个物理口咽模型。目的是制作具有不同尺寸以涵盖成年人群体的模型,并研究口咽尺寸是否会影响不同给药系统的咽部滞留情况。在体外分析中,使用这些模型来确定当从四种吸入给药系统给药药物气雾剂时口咽气腔的滞留效果:一种压力定量吸入器(pMDI)、两种不同的干粉吸入器(DPI A和B)以及一种雾化器。这项工作的目的是确定控制口咽滞留的关键参数以及滞留是否取决于所使用的给药系统。通过测量51个不同的尺寸变量对口咽模型进行表征,从而能够确定每种吸入给药系统中对剂量滞留最具影响力的变量。发现口咽模型滞留情况取决于给药系统(pMDI约等于DPI(A) > DPI(B) > 雾化器)。最具影响力的变量是口咽模型的总体积。已经确定了代表健康成年人高、中、低口咽过滤情况的口咽模型。