This study investigated the effect of formulation parameters on granule properties and growth behavior using a 16 mm twin screw granulator. A model placebo formulation composed of lactose (73.5%), microcrystalline cellulose (20%), hydroxypropylmethyl cellulose (5%) and croscarmellose sodium (1.5%) was used. Variation in the primary particle size was achieved by using three grades of lactose with unique particle size attributes. The incorporation of the binder in a dry versus liquid form was also examined. The granule formation and growth behavior of the different grades of lactose was investigated by varying the liquid to solid (L/S) ratio between 0.15 and 0.45 at 0.05 intervals. The twin screw granulator demonstrated an overall robustness towards remarkable changes in the formulation characteristics, where the three formulation grades displayed similar growth behavior at different L/S ratios. However, granule size analysis demonstrated a bimodal distribution for all formulation grades, with the presence of lumps and un-granulated fines even at the lowest liquid level. This indicated poor liquid distribution inside the granulator, particularly with the liquid addition in a dripping mode and the relatively short residence time available for mixing the different components. The addition of the binder in the liquid phase reduced the level of fines generated in comparison to using binder in the dry form. Granule porosity decreased with the increase in US ratio and percent binder in the liquid phase, indicating more consolidation. The results of this study highlight the need to improve liquid distribution within a twin screw granulator to optimize its utilization in a continuous manufacturing environment. (C) 2012 Elsevier B.V. All rights reserved.