A CFD and experimental investigation of the influence of flow characteristics on spherical agglomeration

Background/Objectives: Spherical agglomeration is a particle size enlargement technique with promise to improve micromeritic properties of active pharmaceutical ingredients. In a spherical agglomeration process, an immiscible bridging liquid is added to suspended crystals, inducing agglomeration. Interaction between primary particles and bridging liquid is essential for agglomeration to occur, and mixing is critical as it influences flow profiles and particle suspension. Benchtop-scale stirred tanks are commonly used for spherical agglomeration research. However, there is little consistency in the tank and impeller design, resulting in limited understanding of the influence mixing has on agglomerate properties. Methods: To inform spherical agglomeration reactor design, four industrial standard impeller geometries promoting differing levels of radial and axial flow in the tank were tested in a 1 L stirred tank at impeller speeds ranging from 300 rpm to 600 rpm. The impeller clearance-to-vessel diameter ratio was varied between 0.18 and 0.33 to determine the influence that impeller characteristics have on spherical agglomerates. Corresponding CFD simulations were conducted in ANSYS Fluent to understand vessel flow patterns with different impeller geometries, speeds and clearances. Results: Experimental results suggest impellers with increased power number produce more consistent agglomerates. CFD simulations showed a clear influence of impeller clearance on particle suspension and velocity profile in the tank. Conclusions: Whilst experimental studies and CFD studies have been conducted for spherical agglomeration, this work provides a systematic investigation that compares both CFD and experimental analysis for industrial standard impeller geometries to understand the important, yet underexamined link between impeller characteristics and spherical agglomerate shape and size.