Quantitative Simulation on Powder Shear Flow Using Discrete Element Method

Abstract

In the pharmaceutical industry, a deep understanding on the physical properties of drug substance (DS) and excipients, such as the powder flowability and compressibility, is critical for the quality control of solid dose drug product (DP). The purpose of this work is to develop a quantitative simulation method to model powder flow by applying the discrete element method (DEM) simulation on the ring shear testing process. A commercially available software Star CCM+ v10.2 by Siemens (New York, NY, USA) was applied as the DEM simulation software. A workstation with Dual CPUs Intel® Xeon® E5-2640 @ 2.50 GHz (24 processors) was applied as the simulation hardware. The Hertz-Mindlin non-slip contact model was applied for particle-particle and particle-wall interactions. The Johnson-Kendall-Roberts (JKR) model was applied to model the cohesion between particles. Original data of powder flowability was measured using the Ring Shear Tester RST-XS by Jenike & Johanson, Inc. (Tyngsborough, MA, USA). The sliding friction coefficient and the work of cohesion were determined as influential parameters on the flowability of DEM particles in the scope of this study. Correlation was established between DEM parameter setting and shear flow behavior of bulk DEM particles by applying multiple linear regression and was verified by comparing simulation with shear flow data of common pharmaceutical excipients. This method is recommended for general formulation and manufacture development of solid dose DP.