This study is concerned with quantifying the effect of primary particle size polydispersity on granule inhomogeneity for fluid-bed granulation. Specifically, it looks at how the variability in the PSD affects key granule properties at the granulation end-point. For the first time, the distribution of primary particles among different size fractions of the final granules was investigated computationally, together with experimental validation. Granulation was carried out from primary particles with the same mean size but different widths of the size distribution and the granules were subsequently "disassembled" both physically and computationally to analyze their composition. The particle size distribution did not have any effect on the size distribution of the granules, but strongly influenced their composition and porosity. Interestingly, the incidence of coarse primary particles (>180 mu m) was highest within the smallest granule size fractions, and conversely, large granules contained predominantly fine (<125 mu m) primary particles. These findings have significant implications for the granulation of heterogeneous powder mixtures (e.g. API and excipient). (C) 2011 Elsevier Ltd. All rights reserved.