Development of a Stochastic Individual Path (SIP) Model for Predicting the Deposition of Pharmaceutical Aerosols: Effects of Turbulence, Polydisperse Aerosol Size, and Evaluation of Multiple Lung Lobes

作者：Longest P Worth^*; Tian Geng; Delvadia Renishkumar; Hindle Michael

来源：Aerosol Science and Technology, 2012, 46(12): 1271-1285.

DOI：10.1080/02786826.2012.708799

In this study, a new computational fluid dynamics (CFD) modeling approach for pharmaceutical aerosols is further developed by evaluating the effects of turbulence, polydisperse aerosol size distribution, and multiple lung lobes on deposition in the mouth-throat (MT) and entire tracheobronchial (TB) airways. To evaluate a range of respiratory drug delivery conditions, a model dry powder inhaler (DPI; Novolizer (TM)) and a model spray soft-mist inhaler (SMI; Respimat (TM)) were considered. The respiratory geometry consisted of a previously developed characteristic MT and complete upper TB geometry through the third bifurcation (B3). More distal TB airways were simulated using stochastic individual path (SIP) models extending into each of the five lung lobes through bifurcation B15. Based on comparisons with new in vitro deposition data, results indicated that the low Reynolds number (LRN) k-omega turbulence model with near-wall corrections for anisotropic turbulence and velocity conditions accurately predicted deposited drug mass from both inhalers. Simulating the polydisperse aerosol size distribution had a large impact on overall deposited drug mass compared with a monodisperse approximation. However, a new equivalent mass median diameter (MMD), calculated as MMDeq = 1.25 x MMD, was shown to provide a good monodisperse estimate of the aerosol deposition from both inhalers considered in this study used with different inhalation flow conditions in the SIP models. Large variations in deposition were observed among the five lung lobes. However, deposition in the left lower lobe (scaled by a factor of 5) was found to be characteristic of total lobar deposition in the range of B4-B15 and allowed for the simulation of only one lobe. Implementing the approximations of an equivalent MMD and simulating deposition in one characteristic lung lobe increased the efficiency of the airway CFD simulations by over 25 times at the expense of a maximum 12% relative error compared with the more exact simulations. As an example of model utility, results indicated that the state-of-the-art SMI improved delivery efficiency of drug by a factor of 1.5 in the upper TB region and by over an order of magnitude in the lower TB airways compared with a commonly used high quality DPI.

• 出版日期2012