Abstract Summary (Max 250 words)
Pharmaceutical formulations containing low bulk density components present challenges in powder flow and handling. High-shear wet granulation (HSWG) is widely used to improve powder handling and produce granules with controlled particle size. The scale-up of HSWG remains challenging due to several stages of the granulation process, such as dry mixing of formulation components and liquid binder addition, which subsequently influence wet mass formation, granule size, and tablet dissolution profile. In this study, Discrete Element Method (DEM) simulations were used to investigate the dry mixing and wetting stages for two different scales of HSWGs. Dry mixing performance was evaluated using Lacey’s Mixing Index (LMI), with both scales showing comparable mixing behaviour, indicating that dry mixing was not a differentiating factor between the scales. During the wetting stage, DEM simulations showed that differences in powder bed structure and particle velocity influence liquid binder distribution. The PMA 300 exhibited a higher powder bed accumulation near the vessel wall, which reduced the effective interaction between the liquid binder spray and the circulating powder bed. Further analysis showed that matching impeller tip speed alone does not ensure similar powder flow dynamics during scale-up. Evaluation using the Froude number demonstrated that maintaining a similar moving powder flow profile provides a more appropriate scale-up criterion. These results demonstrate how DEM-based digital modelling can support the scale-up of wet granulation processes by linking equipment design, operating conditions, and powder flow dynamics.
