Size-induced segregation during pharmaceutical particle die filling assessed by response surface methodology using discrete element method

Discrete element method (DEM) combined with response surface methodology (RSM) was carried out for investigating the segregation behaviour of binary particles during die filling of the pharmaceutical tableting machine, which comprised a horizontally moving die equipped with a vertically moving bottom punch. To achieve accurate particle flow simulations, parameters of the pharmaceutical spherical granules were calibrated using experimental bounced height, rolling distance and angle of repose. These parameters were implemented in the DEM simulations and compared with experimental high-speed camera observations and measurements of the filling ratio. Simulations and experimental results showed reasonable qualitative and quantitative agreement, validating the simulation model. The validated model was employed to evaluate the segregation of binary particle mixtures and RSM was used for analysing the DEM results of the segregation. The RSM revealed that, unlike the die velocity, small particle size, horizontal position and vertical position affected the segregation index significantly. The segregation resulted from percolation of small particles between large particles in the feed shoe and bottom back corner of the die. DEM combined with RSM approach will become significantly efficient method to understand the process for implementing the quality by design approach. (C) 2016 Elsevier B.V. All rights reserved.