This study is concerned with the development of a novel population balance model (PBM) framework that can qualitatively capture the dynamics of a continuous powder mixing process. For the first time, a PBM has been developed to model powder mixing and it accounts for key design and process parameters such as mixer RPM, processing angle in terms of powder fluxes, along with the effect of number of axial and radial compartments. Via this approach, results clearly show the qualitative validity of the PBM as a tool to capture the dynamics of the process that affect API composition, RSD and RTD. The model also demonstrates the use of the PBM as an overall multi-scale modeling tool to combine micro-level models such as DEM in a hybrid framework. Due to the relative computational simplicity of solving the PBM (as compared to DEM), the developed model can be used effectively in control and optimization of the mixing process. (C) 2012 The Society of Powder Technology Japan. Published by Elsevier B.V. and The Society of Powder Technology Japan. All rights reserved.