The compression behavior of binary mixtures with a large size disparity has been investigated using an instrumented tableting emulator. The stress-strain correlations obtained during the compaction of blends of microcrystalline cellulose and varying amounts of micronized active ingredient have been analyzed in order to identify the nature of the phenomena controlling the densification of the different ingredients throughout the tableting process. It has been discovered that, cocurrently to the elastic and plastic deformation of the excipient, the API particles can migrate into the intrinsic void spaces of the powder bed. This secondary rearrangement step occurs on a characteristic time scale and, therefore, exhibits a strong sensitivity to the speed of compaction. The implications of this phenomenon can be far reaching, with the most significant impact manifesting in the area of tablet weight control. Most currently-implemented tableting control schemes (usually found in development and research-scale devices) rely on empirical models correlating compaction force measured by the tablet press instrumentation to the composition/mass of powder in the die. Based on these correlations the die-fill settings can be adjusted to maintain tablet weight. Since the secondary rearrangement mechanism effectively shields the smaller particles from deformation, their mass cannot be detected by the strain gauges measuring compaction force, which renders the control scheme unreliable. (C) 2012 Elsevier B.V. All rights reserved.