Walenga Ross L, Longest P Worth
Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, Virginia 23284.
Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, Virginia 23284; Department of Pharmaceutics, Virginia Commonwealth University, Richmond, Virginia 23284.
J Pharm Sci. 2016 Jan;105(1):147-59. doi: 10.1016/j.xphs.2015.11.027. Epub 2016 Jan 13.
To evaluate the regional delivery of conventional aerosol medications, a new whole-lung computational fluid dynamics modeling approach was applied for metered dose inhaler (MDI) and dry powder inhaler (DPI) aerosols delivered to healthy and constricted airways. The computational fluid dynamics approach included complete airways through the third respiratory bifurcation (B3) and applied the new stochastic individual pathway modeling technique beyond B3 through the remainder of the conducting airways together with a new model of deposition in the alveolar region. Bronchiolar (B8-B15) deposition fraction values were low (∼1%) for both MDI and DPI aerosols with the healthy geometry, whereas delivery to the constricted model was even lower, with deposition fraction values of 0.89% and 0.81% for the MDI and DPI, respectively. Calculating dose per unit surface area for the commercial MDI and DPI products resulted in approximately 10(-3) μg/cm(2) in the lower tracheobronchial region of B8-B15 and 10(-4) μg/cm(2) in the alveolar region. Across the lung, dose per unit surface area varied by 2 orders of magnitude, which increased to 4 orders of magnitude when the mouth-throat region was included. The MDI and DPI both provided very low drug dose per unit surface area to the small tracheobronchial and alveolar airways.
为评估传统气雾剂药物的区域递送情况,一种新的全肺计算流体动力学建模方法被应用于定量吸入器(MDI)和干粉吸入器(DPI)递送至健康和狭窄气道的气雾剂。计算流体动力学方法包括完整的气道直至第三级呼吸分支(B3),并在B3之后通过传导气道的其余部分应用新的随机个体路径建模技术以及肺泡区域沉积的新模型。对于具有健康几何形状的MDI和DPI气雾剂,细支气管(B8 - B15)沉积分数值较低(约1%),而在狭窄模型中的递送更低,MDI和DPI的沉积分数值分别为0.89%和0.81%。计算商业MDI和DPI产品的单位表面积剂量,在B8 - B15的下气管支气管区域约为10^(-3) μg/cm²,在肺泡区域约为10^(-4) μg/cm²。在整个肺部,单位表面积剂量变化了2个数量级,当包括口咽区域时增加到4个数量级。MDI和DPI向小气管支气管和肺泡气道提供的单位表面积药物剂量都非常低。