In pharmaceutical industry, a deep understanding on the physical properties of drug substance and excipients is critical for the quality control of solid dose drug product. The purpose of this work is to develop a quantitative simulation calibration and prediction platform to model powder compression by applying the Discrete Element Method (DEM). The Luding elasto-plastic contact model was applied for particle-particle interactions. The loading stiffness, the unloading stiffness ratio, and the particle density (which served by adjusting the bulk volume of a specificmass of particles) were determined as influential parameters in this study. Calibration was established between DEM parameters and compression profile of pharmaceutical powders in a short timeframe. This platform could capture the main compressibility characteristics of pharmaceutical materials and could successfully provide quantitative predictions on compression profiles of mixtures. It was recommended for development of solid dose DP especially when the amount of DS was limited. (C) 2020 Elsevier B.V. All rights reserved.