Comparative Assessment of Computational vs. In Vitro Methods for the Estimation of Dry Powders for Inhalation Emitted Fraction

Emitted fraction (EF) is one of the critical quality attributes of dry powders for inhalation (DPIs). Traditionally, different in vitro methods have been used for the assessment of DPIs EF. However, the evolution in computer-based (in silico) methods led to the development of special fields, such as Computational Fluid Dynamics (CFD) coupled with fluid-particle dynamics models e.g., Discrete Phase Model (DPM) as a useful alternative for the assessment of DPIs aerodynamic performance. The aim of this study was to design a CFD-DPM model for the prediction of model DPIs EF, and assess the prediction power of this method by comparing the in silico prediction results with in vitro determined EF values, obtained by three different methods. The EFs of the solid lipid microparticles (SLM) DPIs were determined in vitro by Twin stage impinger, Next generation impactor and Fast Screening Impactor. CFD-DPM model was successfully designed, and then the simulation results indicated the percentage of particles that remained in the inhaler. Based on those data, DPI EFs were calculated to be in the range of 83 % and 92%, indicating that CFD-DPM simulations were able to catch the differences between five SLM DPI formulations. In addition, CFD-DPM predicted the regional particle deposition in the inhaler, which cannot be precisely determined based on in vitro experiments. CFD-DPM predicted EF values were generally comparable to the EF values obtained by three in vitro methods, although some differences were observed between in vitro and in silico values. Therefore, it can be concluded that although additional improvements of CFD-DPM designed model are still necessary in order to be able to precisely describe aerodynamic performance of SLM DPIs, CFD-DPM modeling can be considered as a very useful tool in DPIs development.