Wet granulation processes typically start with a dry premixing stage in which the objective is to homogenize and prepare the powder materials for further granulation stages. This work was aimed at studying the influence of premixing conditions on the wettability of formulations that contain hydrophobic components and the potential implications on early granulation stages. A binary lactose-based formulation was chosen as the model system and magnesium stearate (MgSt) as the hydrophobic ingredient The formulations were processed in a laboratory-scale high shear granulator according to a factorial experimental design to evaluate the effect of MgSt concentrations and applied premixing shear strains on the hydrophobicity of the formulation. The experimental design included five concentrations of MgSt (from 0% to 3% w/w) and three levels of applied shear strain ranging from 450 to 1800 blade passes (bp). A modified Washburn method was implemented to determine the hydrophobicity of blend samples after the premixing and hyperspectral images, collected with a NIR Chemical Imaging (NIR-CI), were used to assess the spatial dispersion of MgSt. Statistical results demonstrated that both studied factors increase the hydrophobicity of the formulation and suggest that the magnitude of this effect depends on the mixing mechanism of the hydrophobic ingredient. The findings can be of interest in the formulation and process design to modify the wettability of hydrophobic blends before granulation. (C) 2015 Elsevier B.V. All rights reserved.