School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia 23298-0533, USA.
J Aerosol Med Pulm Drug Deliv. 2010 Dec;23 Suppl 2:S59-69. doi: 10.1089/jamp.2010.0846.
In order to answer the question "what research remains to be done?" we review the current state of the art in pharmaceutical aerosol deposition modeling and explore possible in vivo- in vitro correlations (IVIVC) linking drug deposition in the human lung to predictions made using in vitro physical airway models and in silico computer models. The use of physical replicas of portions of the respiratory tract is considered, alongside the advantages and disadvantages of the different imaging methods used to obtain their dimensions. The use of airway replicas to determine drug deposition in vitro is discussed and compared with the predictions from different empirical curve fits to long-standing in vivo deposition data for monodisperse aerosols. The use of improved computational models and three-dimensional computational fluid dynamics (CFD) to predict aerosol deposition within the respiratory tract is examined. CFD's ability to predict both drug deposition from pharmaceutical aerosol sprays and powder behavior in dry powder inhalers is examined; both were highlighted as important areas for future research. Although the authors note the abilities of current in vitro and in silico methods to predict in vivo data, a number of limitations remain. These include our present inability to either image or replicate all but the most proximal airways in sufficient spatial and temporal detail to allow full capture of the fluid and aerosol mechanics in these regions. In addition, the highly complex microscale behavior of aerosols within inhalers and the respiratory tract places extreme computational demands on in silico methods. When the complexity of variations in respiratory tract geometry is associated with additional factors such as breathing pattern, age, disease state, postural position, and patient-device interaction are all considered, it is clear that further research is required before the prediction of all aspects of inhaled pharmaceutical aerosol deposition is possible.
为了回答“还有哪些研究工作要做？”这个问题，我们回顾了药物气溶胶沉积建模的当前现状，并探讨了将药物在人体肺部的沉积与使用体外物理气道模型和计算机模型进行预测的体内-体外相关性（IVIVC）。我们考虑了使用呼吸道部分的物理复制品，以及使用不同的成像方法来获取其尺寸的优缺点。讨论了使用气道复制品来确定体外药物沉积，并将其与不同经验曲线拟合对单分散气溶胶的长期体内沉积数据的预测进行了比较。还研究了使用改进的计算模型和三维计算流体动力学（CFD）来预测呼吸道内的气溶胶沉积。检查了 CFD 预测药物从药物气溶胶喷雾器沉积和干粉吸入器中粉末行为的能力；这两者都被认为是未来研究的重要领域。尽管作者注意到当前的体外和计算方法能够预测体内数据，但仍存在一些局限性。这些包括我们目前无法对所有但最接近的气道进行足够的空间和时间细节成像或复制，以允许充分捕获这些区域中的流体和气溶胶力学。此外，干粉吸入器和呼吸道内气溶胶的高度复杂的微观行为对计算方法提出了极高的要求。当与呼吸模式、年龄、疾病状态、姿势位置和患者-设备相互作用等其他因素相关的气道几何形状的变化复杂性被考虑在内时，很明显，在能够预测吸入药物气溶胶沉积的所有方面之前，还需要进一步研究。
