Mechanistic modelling of spherical agglomeration processes

Spherical agglomeration is emerging as an important unit process for pharmaceutical manufacturing. However, at present, quantitative process design to control agglomerate attributes is impossible. A new population balance model to predict agglomerate attributes is presented where for the first time, all of the key rate processes that control agglomerate properties are included. A parameter sensitivity analysis is undertaken to study the effect of process parameters on agglomerate attributes. Bridging liquid droplet size and bridging liquid to solids ratio (BSR) are critical controlling parameters. Good quality agglomerates are formed over a relatively narrow range of BSR. Within this range, bridging liquid droplet size can be used to tune agglomerate size. Primary crystal size and process mixing intensity have only a modest effect on equilibrium agglomerate attributes but do impact agglomerate formation kinetics. This new model provides the basis for improved process understanding and quantitative process design of spherical agglomeration.