In this study, a novel multi-component population balance model (PBM) for the twin-screw granulation (TSG) process was developed, taking into account the rate processes of aggregation, breakage, liquid addition, and consolidation. Interactions between multiple solid components (e.g. active pharmaceutical ingredient and excipient) and the amount of liquid were accounted for in quantifying the aggregation and breakage rates. Experimental data was obtained for the TSG process, whereby the effect of initial particle size distribution and liquid-to-solid ratios on key granule properties was studied. The data was used to estimate adjustable parameters in the proposed mechanistic kernels and to validate the calibrated process model as a predictive tool. The simulation results showed a good agreement with experimental data. (C) 2014 Elsevier B.V. All rights reserved.