Spherical agglomeration kinetics: a mechanistic approach

Spherical agglomeration, a process of in-suspension particle size enlargement, can substantially improve critical quality attributes of powders. In this work, a paracetamol-heptane-water system is used to investigate the kinetics of spherical agglomeration, demonstrating for the first time the influence of true bridging liquid to solid ratio (TBSR) and suspension loading on the evolving size, shape and density of agglomerates. A critical range of TBSR is identified where robust agglomerates are formed that are round, moderately dense, and have a controlled size distribution. Immersion nucleation, drop breakage, and agglomerate densification by impact are the controlling rate processes. Increasing mixing intensity reduces agglomerate size, porosity and agglomeration time. Increasing solids loading increases agglomeration time while yielding smaller agglomerates with lower porosity. A first order consolidation model quantitatively predicts the agglomeration kinetics as well as agglomerate properties with increasing TBSR, and is a powerful tool for design and scale up.