Application of the Discrete Element Method for Manufacturing Process Simulation in the Pharmaceutical Industry

Abstract

Process simulation using mathematical modeling tools is becoming more common in the pharmaceutical industry. A mechanistic model is a mathematical modeling tool that can enhance process understanding, reduce experimentation cost and improve product quality. A commonly used mechanistic modeling approach for powder is the discrete element method (DEM). Most pharmaceutical materials have powder or granular material. Therefore, DEM might be widely applied in the pharmaceutical industry. This review focused on the basic elements of DEM and its implementations in pharmaceutical manufacturing simulation. Contact models and input parameters are essential elements in DEM simulation. Contact models computed contact forces acting on the particle-particle and particle-geometry interactions. Input parameters were divided into two types—material properties and interaction parameters. Various calibration methods were presented to define the interaction parameters of pharmaceutical materials. Several applications of DEM simulation in pharmaceutical manufacturing processes, such as milling, blending, granulation and coating, were categorized and summarized. Based on this review, DEM simulation might provide a systematic process understanding and process control to ensure the quality of a drug product.

Comparative 3D DEM simulations of sand–structure interfaces with similarly shaped clumps versus spheres with contact moments

“…A simple linear elastic normal contact was chosen to capture on average various contact possibilities present in real sands [39] and to reduce the computation time [67]. We performed comparative simulations for spheres with contact moments between a linear and nonlinear contact model [36] following Hertz [18] and Mindlin and Deresiewicz [35], based on a plane compression test without shear localization.…”

“…5). Although a nonlinear contact model is more realistic (in particular for small loads) [39], a linear elastic contact law provides similar DEM results with the significantly reduced computation time [67] and therefore was used in current simulations. The elastic constants of the grain contact in our DEM model do not correspond to the elastic constants of the spheres' material in the Hertz law (the parameter K n in Eq.…”

Simulation of flow properties of differently shaped particles using the discrete element method

“…The particles are allowed to overlap one another during a few time intervals. The flowchart of DEM simulation is illustrated in Figure 3 [49].…”

Control Strategy for Process Development of High-Shear Wet Granulation and Roller Compaction to Prepare a Combination Drug Using Integrated Quality by Design

“…The empirical models are used to identify the relationship between input (control factors) and output variables (response factors) [ 5 ]. Empirical models include multivariate analysis (MVA), design of experiment (DoE), and process analytical technology (PAT) based on empirical, semi-empirical, or statistical methods [ 6 ]. Physics-based models include the discrete element model, computational fluid dynamics, the finite element method, and hybrid models [ 5 ].…”