(461a) Influence of Impeller Geometry on the Formation of Spherical Agglomerates

Spherical agglomeration is a promising particle size enlargement technique for pharmaceutical manufacturing, with ongoing research for industrial applications. In spherical agglomeration the primary crystals are suspended in a solvent system and a bridging liquid is added to create agglomerates. Most research is conducted at bench-top scale, with small stirred tanks commonly used for spherical agglomerate production. While the effect of scale and impeller geometry is known to have strong effects on flow patterns and fluid and particle velocity profiles for suspensions in stirred tanks, little investigation has been conducted on these parameters for spherical agglomeration.

To investigate the effect of impeller configuration on spherical agglomeration, computational fluid dynamics (CFD) simulations were performed using ANSYS Fluent 19.1. Impeller geometries, clearances, and speeds were varied. Flat-blade, pitched-blade, Rushton turbine, and a propeller impellers were tested. These impellers were selected to vary the relative contributions of axial and radial flow on the velocity profile of the stirred tank. The geometry constructed for the CFD simulations was a replication of a 1L stirred tank, used for complementary spherical agglomeration experiments. Standard geometric relationships for stirred tank design were used to determine the impeller clearances; tested clearances are between 1/5 to 1/3 of the tank diameter. Each impeller geometry and clearance were simulated for impeller speeds of 300rpm, 450rpm, and 600rpm.

For the experiments, a suspension of monosized 52μm PMMA plastic beads in water was used as model suspended particles, and toluene was added as a bridging liquid.

Increasing the impeller speed resulted in more spherical and denser agglomerates as increased collision velocity increases the rate of agglomeration and consolidation. Collision velocity also increased when radial flow was promoted in the tank; such as when a Rushton turbine or flat-blade impeller was used.

Lower clearances resulted in a broad particle size distribution; containing unagglomerated primary material and large, dense agglomerates which sank to the bottom of the tank, closer to the impeller flow field. Here they contacted more bridging liquid, increasing growth. This is more apparent at lower impeller speeds as there is insufficient shear to break the larger agglomerates and the velocities further away from the impeller are not high enough to allow for the smaller particles to become entrained in the flow field. This demonstrates that the clearance has a significant impact on mixing efficiency.

The CFD results have been useful to understand the flow behaviours in the stirred tank under the various operating conditions; and how these have influenced the formation of spherical agglomerates. Even though impellers induce the same type of flow in the tank the agglomerates do not undergo the same velocity or shear stress profiles, resulting in differences in the agglomerate formation. The results of the CFD simulations will be used to inform the derivation of an agglomeration kernel that will be implemented into a population balance model (PBM) for spherical agglomeration. This is done with the intention to predict ideal impeller design to produce spherical agglomerates with desired characteristics.