(303f) Discrete Element Modeling of the Role of Shear Rate, Fill Level, Scale, and Equipment Design on High Shear Wet Granulation (HSWG) Processes

Remy, B., Bristol-Myers Squibb Co.
Dubey, A., Tridiagonal Solutions Inc.
Cole, S., DEM Solutions Ltd.
LaRoche, R. D., DEM Solutions USA Inc.
Narang, A., Bristol-Myers Squibb

Wet granulation is a commonly employed unit operation in the pharmaceutical manufacturing of many oral solid dosage products. Several mechanisms are at play during wet granulation. These include wetting and nucleation, growth and consolidation, and breakage/attrition. Being a complex process makes it difficult to describe mathematically all the associated physical sub-phenomena. However, it is possible to decouple certain aspects and analyze them using computational techniques. Using numerical modelling tools, studies were performed to understand the effect of tip speed (shear rate), fill level, granulator scale and design on particle velocities and stress profiles. The discrete element method (DEM) was used to discretize the powder particles as elements suitable for computational analysis. Element computational calibration was performed to ensure that the elements represent a typical pharmaceutical excipient (microcrystalline cellulose). The studies provide a quantitative relationship between the process variables (impeller tip speed, granulator fill level, granulator design and equipment scale) and measurable properties (velocity profiles, normal, and shear stress distribution) in the radial, tangential and axial directions. The DEM simulations showed that impeller tip speed had the most significant effect on resulting particle velocities while fill level, granulator design and equipment scale had minimal impact on particle velocities. Normal and shear stress distribution were affected by impeller tip speed, fill level and equipment scale while granulator design had minimal impact. By numerical calculations of pressure, velocity, and shear stress in different regions of the granulator, this study provides guidelines on achieving reproducible particle environment with change in scale, device design, fill level, and speed.