The segregation phenomena is one of the most important problems in tablet press machines, as it can induce an incorrect composition of the tablets and, thereby, modify its mechanical or physical properties. For that reason, the purpose of this work is to analyze the segregation of a binary mixture that is produced in the tank of a prototype of a rotary tablet press machine with gravity feeder using the discrete element method (DEM). For that purpose, a DEM simulation model was used to identify the mechanisms of segregation in several tanks of differing shapes with two widths and various filling and feeding methods. Thus, it was possible to determine that the segregation index (SI) that was obtained in the Short design was the lowest, regardless of the width of the tank or the method of feeding that was used. Moreover, by analyzing the effect of the width and the method of feeding the tanks, it can be concluded that it is possible to predict the segregation that is created in the prototype of a rotary tablet press machine with gravity feeder by a simplified simulation model (in which a narrow tank is filled once) that reduces the simulation time by 95%. (C) 2018 Elsevier B.V. All rights reserved.