The objective of this study was to investigate the mutual interaction behavior of magnesium stearate (MgSt) and colloidal silica (CS) affecting their smear coating phenomena on excipient and active ingredient particles during shear mixing of pharmaceutical blends. Multiple pharmaceutical blends were processed in a v-blender under high shear condition by simultaneously varying the mixing orders of blends and concentration of additives. Uniformity of smeared patterns of additives was found to be affected by the physical and chemical nature of excipient surfaces. Although, an increase in concentration of lubricant in the formulation increased the amount of smeared lubricant coating on surrounding particles, the hydrophobic behavior was found to be predominantly dependent upon the order of mixing of constituent components of additives. More interestingly, prior mixing of the blend with MgSt followed by other components although increased the smearing area, surprisingly decreased the hydrophobic behavior, indicating a strong interaction parametric effect of MgSt with CS. For the first time, this work successfully demonstrated the limits of additive concentration in the blends governing the smearing at nanoscale. A phenomenal increase in nanosmearing area of CS compared to MgSt also prolonged the dissolution of tablets, indicating a strong interaction effect of both additives at nanoscale. (C) 2014 Elsevier B.V. All rights reserved.