Structural changes in selected pharmaceutical blends under high process shear and distribution of their constituent additives during tablet compaction were investigated as a function of lubricant composition. An unexpectedly strong influence of shear on the distribution of additives in tablets was found. Pharmaceutical formulations containing avicel 102, pharmatose, micronized acetaminophen and magnesium stearate (MS) were mixed in a v-blender. The shell speed of the blender was maintained at 15 rpm and the intensifier bar was varied between 25, 525 and 1000 rpm. Two sets of blends were prepared by varying the lubricant composition between 0.5 and 1% by weight. The mixing of the blend for each composition of lubricant was performed three times for duration of 5, 10 and 20 min. Tablets were compressed in a rotary tablet press at a compression force of 8 kN. Another set of blends mixed with both MS and colloidal silica (CS) was processed in a shear rheometer. Interestingly, results indicated that the effect of hydrophobic phenomena as a function of lubricant composition was found to influence electrostatic properties, physical behavior and tablet hardness. Hydrophobicity was found to increase with lubricant composition and process shear. Independent of the lubricant composition, average tablet hardness decreased with an increase in hydrophobic and electrostatic phenomena of the blend. Increase in the lubricant content decreased the average hardness of tablets. In addition, distribution of additives in tablets was found to be non-uniform. More interestingly, the distribution of CS was found to be dominant over MS within the tablet at high shear. Surprisingly, due to the physical compression force exerted on tablets, a partial structural transformation of powders was found for blends processed under high shear. (C) 2014 Elsevier B.V. All rights reserved.