Towards quantitative prediction of the performance of dry powder inhalers by multi-scale simulations and experiments

In Silico Methods for Development of Generic Drug–Device Combination Orally Inhaled Drug Products

“…56 A follow-up study by Tong et al 57 used a CFD-DEM approach to further investigate the impact of API-carrier ratios on the FPF of albuterol sulfate formulations, where it was concluded that by increasing API-carrier ratio the aerosolization efficiency was increased, but the improvement was dependent on carrier size. Recently, Nguyen et al 58 measured the FPF from two devices with the same budesonide formulation using in vitro techniques, where CFD-DEM simulations used a semiempirical approach to provide apparent surface energy of a given formulation to provide predictions that were reasonably close to the measured values of FPF. The efficiency of agglomerate-agglomerate collisions was investigated by Tong et al 59 using a CFD-DEM approach, as illustrated in Figure 3, where a correlation based on the ratio of collision to cohesion energy was able to describe differences in FPF according to differences in air inlet velocity, the Hamaker constant, and collision angle, which may be useful for guiding device design.…”

“…Early development of these models focused on mathematical relationships to characterize particle–particle and particle–wall phenomena such as van der Waals, electrostatic, capillary, and contact forces as well as particle–fluid interactions, whereas some models that actually modeled DPI drug delivery were newly available at the time of those reviews . Since 2015, when those reviews were published, several studies involving CFD‐DEM based models that consider DPI delivery have been published . Leung et al .…”

“…used a CFD‐DEM approach to further investigate the impact of API‐carrier ratios on the FPF of albuterol sulfate formulations, where it was concluded that by increasing API‐carrier ratio the aerosolization efficiency was increased, but the improvement was dependent on carrier size. Recently, Nguyen et al . measured the FPF from two devices with the same budesonide formulation using in vitro techniques, where CFD‐DEM simulations used a semiempirical approach to provide apparent surface energy of a given formulation to provide predictions that were reasonably close to the measured values of FPF.…”

“…19,20 Since 2015, when those reviews were published, several studies involving CFD-DEM based models that consider DPI delivery have been published. [56][57][58][59][60][61][62] Leung et al 56 investigated the effect of two mouthpiece grid mesh designs on FPF of four different albuterol sulfate formulations from an Aerolizer DPI using an in vitro method. By switching from the original grid mesh to a cross-grid design, FPF was reduced for drugonly and 1:5 and 1:10 API-carrier ratio formulations, but not for a 1:100 API-carrier ratio formulation, where corresponding CFD-DEM simulations were able to describe the complex relationship between flow and impaction differences caused by the switch in mesh designs that explained differences in Figure 3 Velocity contours and breakup patterns of agglomerate-agglomerate collision as predicted by Tong et al 59 at times of (a) 0, (b) 0.15, (c) 0.26, and (d) 0.33 seconds after particle release.…”

Comparative Assessment of In Vitro and In Silico Methods for Aerodynamic Characterization of Powders for Inhalation

“…However, intrinsic differences between various in vitro, and in vitro and in silico methods complicate direct comparison between experimental and simulated data. A number of studies in parallel assessed the results of CFD simulations and in vitro experimental results (usually including a single in vitro method such as MSLI, NGI or ACI) [35][36][37][38][39]41,[44][45][46][47][48][49][50][51][52][53]. Overall, some correlation between in vitro and in silico CFD results has been detected [48][49][50][51][52][53], but there is a need for additional comparative assessment of CFD tools in relation to the in vitro methods to evaluate the applicability of CFD in the research and development of various DPI formulations.…”