Advances in Discrete Element Modeling of High-Shear Wet Granulation Process Using Rocky-DEM

High-shear wet granulation process is widely used in the pharmaceutical industry to improve the bulk density and flow characteristics of a formulation. There are different particle-level phenomenon and mechanisms at play during a granulation process, such as nucleation, agglomeration and breakage. The challenge is to ensure that these mechanisms occur similarly at different scales of the granulator to keep consistency in the quality of the granules. The ability to accurately predict the stress and collisional behavior in a granulator, would not only help our fundamental understanding of the process but also help alleviate experimental costs during scale-up studies.

Discrete element method (DEM) is a valuable tool to model such particle-level interactions, but in the past, has suffered from practically restrictive run times. In order to circumvent this, assumptions on particle size and shape (modeled as spheres or glued-spheres) were routinely made. However, more recently, advances in DEM technology, such as that provided by software Rocky-DEM, have addressed some of these limitations. Rocky-DEM provides a step-change in the ability to perform large scale DEM simulations significantly faster by utilizing the large number of cores available in NVIDIA® graphics card (GPU processing). The simulation run times using the GPU were compared with traditional and more expensive CPU solvers.  In addition, several capabilities unique to Rocky-DEM in comparison with other commercially available DEM codes were utilized in this study; a few of them include the representation of Avicel using non-spherical particle shapes (polyhedral shape representation) and the ability to include cohesive forces and breakage without loss of mass or volume.

Rocky-DEM was used to predict the movement of Avicel particles in a Diosna® granulator at 50% volume fill (Figure 1).  The simulations were validated by comparing results to experimentally-obtained surface velocity profile measurements using video-imaging.   The validated DEM model was then used to establish a relationship between various parameters on simulation measurements of bulk properties (such as average velocity and stress distributions in the powder).  Some of the variables included the particle stiffness (low and high), particle shape (spherical vs Avicel-shaped), particle size (0.8, 1.8 mm), impeller speed (Froude number vs tip speed), granulation type (wet vs dry particles), and granulator scale (1L, 10L and 150L). Thus, by numerically predicting granular pressures, velocities, and stresses in different regions of the granulator, this study provides guidelines on achieving reproducible particle environments with changes in scale and impeller speeds, and establishes the effect of particle shape and size. The Rocky DEM platform enabled the utilization of actual particle shapes and sizes in these studies and therefore are a closer reflection of a real-case scenario.

Figure 1. A cross-section of the granulator colored by the particle initial fill position to show mixing profiles