The aim of this study was to apply the knowledge of surface free energy for the flowability prediction of pharmaceutical excipients. In order to predict the flowability, the spreading coefficient was calculated from the surface free energy of each material using Wu's equation. The resulting spreading coefficient could indicate which material would spread over another in a binary mixture. In this study, the binary mixture consisted of filler (lactose, or dibasic calcium phosphate) and a lubricant (magnesium stearate), talc or silicon dioxide. The flowability of each binary mixture was assessed using angle of repose and compressibility index data. Finally, the resulting spreading behavior was compared with flowability parameters. The calculated spreading coefficient values revealed that magnesium stearate, talc and silicon dioxide would spread over the surface of lactose and dibasic calcium phosphate. The evaluated flowability from the two methods found that all of the lubricants could improve the flowability of the binary mixtures. Moreover, these results were in accordance with predictions. In conclusion, the spreading coefficient could be a suitable tool for predicting the flowability of powder mixtures.