Densification process of granules from roll-compacted binary mixtures of microcrystalline cellulose, known as ductile powder, and lactose, considered a brittle material, was investigated using a full-instrumented die press. The role of each component and the effect of the granule size on tablet properties were analysed. Based on the stress transmission measurements in axial and radial directions, the densification behaviour of granules and original mixtures was studied and correlated to the deformation mechanisms of the granules. Results showed that tablets produced with granules presented lower tensile strength than the tablets produced with the original binary mixtures. Attending the granule size, an increase in the size was translated into a reduction of tensile strength of tablet. The analysis of the axial stress transmission ratio, which measures the loss of stress from the top to the bottom of the powder bed, showed a lower value for granules than for the original mixtures. This difference was attributed to the work consumed in the fragmentation of granules during the densification process. However, the granules fragmentation limits the development of large contact surface between particles and results in lower tablet's strength. Moreover, the reduction of tensile strength was more significant for a high percentage of the ductile material in the mixture. In order to reduce the effect of loss of reworkability, quality by design should be applied from the process development and formulation perspectives. (C) 2015 Elsevier B.V. All rights reserved.