The effect of primary particle surface wettability by a binder solution on the rate of agglomeration in a fluid-bed top-spray granulation process was investigated. A model system consisting of hydrophilic and hydrophobic spherical primary particles with a narrow size distribution, and an aqueous solution of hydroxy propyl-cellulose (HPC) as binder, was used. The surface energy of the primary particles was measured by inverse gas chromatography (IGC) and their wettability was characterised by static and dynamic contact angle. Granulation was carried out in a desktop fluid-bed granulator and the resulting granule size distribution and granule microstructure were analysed. The hydrophobic particles gave a wider granule size distribution (larger maximum granule size) than hydrophilic ones under otherwise identical conditions, and the granules were notably rounder and more compact. However, the fraction of un-granulated fines was also higher in the case of hydrophobic primary particles. SEM analysis of granule microstructure revealed that the hydrophilic particles were coated by the binder solution, which left a smaller amount of binder available to form bonds at particle contacts. On the other hand, all of the binder was found to form solid bridges in the case of hydrophobic primary particles. A population balance model was used to explain the observed granulation behaviour. (c) 2006 Elsevier B.V. All rights reserved.