The die filing process within a lab-scale rotary tablet press is simulated using the Discrete Element Method (DEM). Powder is transferred from a gravity feeder (comprising of a cylindrical pipe, an inclined chute, and a rectangular box) into rotating dies. Spherical shape micro-crystalline cellulose particles serve as an experimental pendant to measure the particle size distribution (PSD) and to calibrate the micro-mechanical material properties entering in the DEM calculations. At first, the die filling process of the particles having poly-dispersity in size is explored by analyzing the basic metrics such as tablet mass, tablet mass variation, and mass flow rate. Particle size segregation is investigated by computing the PSD development in different locations of the feeding system and in the filled dies. In addition, particles' velocity and coloring analysis (both qualitative and quantitative) are performed. Results show that different zones of the system are involved in various powder flow phenomena constituting varying particle size segregation causes. Next, the micro-mechanical properties, namely inter-particle cohesion, particle-particle and particle-wall friction, are varied one at a time to shed light on their influence on the particle size segregation and tablet quality. Finally, the influence of different material properties on various metrics are compared with each other providing a guide towards formulation optimization resulting in optimal tableting process performance. (C) 2017 The Society of Powder Technology Japan. Published by Elsevier B.V. and The Society of Powder Technology Japan. All rights reserved.