This paper elucidates the important role of numerical technique in investigating powder dispersion mechanisms in pharmaceutical dry powder inhalers, using the commercial Aerolizer as a model inhaler device. A coupled computational fluid dynamics (CFD) and discrete element method (DEM) technique was adopted to simulate fluid flow and particles, respectively. The shear stress of turbulent flow had no visible effect on powder dispersion while the agglomerate-agglomerate interactions occurred only when the agglomerates were ejected from the capsule. Multiple major impactions occurred between the agglomerates and the chamber wall, which fragmented the agglomerates into large pieces without generating many fine particles. The subsequent impactions between the fragments with the grid were identified as the key factor for the dramatic increase in FPF (i.e. amount of fine particles below 5 pm in the aerosol). The inhaler was more efficient with increasing air flow rate in terms of the FPF, but its performance decreased at a higher flow of 130 Lmin(-1) due to much larger depositions (i.e. increased device retention). This work has demonstrated the capability of CFD-DEM modeling to study various dispersion mechanisms and their relative importance, which provides a rational basis for future improvement of inhaler devices. (C) 2012 Elsevier B.V. All rights reserved.