In powder mixtures, the interactions between the particles are determined by the forces of adhesion and cohesion. The size and the specific surface area of the particles are also determinative factors in the interparticle interactions. The aim of the present work was to investigate the surface properties of different physical mixtures of meloxicam (ME) and find a possible relation between surface properties and dissolution of physical mixtures. The contact angle, surface free energy, polarity, work of adhesion, and work of cohesion of the drug, the carrier, and their physical mixtures were calculated. ME samples with different particle sizes were investigated without the carrier and in two different ratios with mannitol. A smaller (micronized) particle size without the carrier did not improve the dissolution of the drug. However, with the ideal particle size of the drug (ME2) and the ideal ratio of ME and mannitol (1: 10), total dissolution of drug was achieved. In this case, mannitol functioned as a core covered with a monolayer of ME particles. The contact angle, the surface free energy, the polarity, and the work of adhesion can be used as critical parameters to characterization of a powder mixtures and determination of optimum dissolution profile.