Design of Experiments for Optimization of the Lactose Spherical Crystallization Process.

This study provides a comprehensive assessment of the parameters of the spherical crystallization process and their impact on the micromeritic properties of lactose spherical agglomerates. A recently introduced definitive screening design was used to study various process parameters, with particular focus on building predictive models. The parameters included were: lactose solution concentration; volume ratio between the antisolvent and the whole crystallization system; crystallization system temperature; velocity of the addition of the lactose water solution; agitation velocity; and agitation time after whole addition of the lactose solution. Their effects on process yield, particle size parameters D10, D50 and D90, particle size distribution, morphological properties (roundness, solidity) and Hausner ratio were studied. Active effects were identified for all of these responses, with quadratic and interaction effects included. Lactose concentration, volume ratio, crystallization system temperature, and agitation velocity were identified as critical process parameters. For every response, a statistical model was built, where those for Hausner ratio, yield and roundness provided the best predictive performances. Based on these models, D10 and yield were successfully optimized. Definitive screening design proved as useful especially in the screening phase; however, additional experiments are needed to build models with high predictive power for all of these responses.