Crystallization Diagram for Antisolvent Crystallization of Lactose: Using Design of Experiments to Investigate Continuous Mixing-Induced Supersaturation

This study investigates the effects of key process parameters of continuous mixing-induced supersaturation on the antisolvent crystallization of lactose using D-optimal Design of Experiments (DoE). Aqueous solutions of lactose were mixed isothermally with antisolvents Using concentric capillary mixer. Process parameters investigated were the choice of antisolvent (acetone or isopropanol), concentration of lactose solution, total mass flow rate, and the ratio of mass flow rates of lactose solution and antisolvent. Using a D-optimal DoE a statistically significant sample set was chosen to explore and quantify the effects of these parameters. The responses measured Were the solid state of the lactose, crystallized, induction time, solid yield and particle size. Mixtures of alpha-lactose monohydrate and beta-lactose were crystallized tinder most conditions with beta-lactose content increasing with increasing amount of antisolvent. Pure alpha-lactose monohydrate was crystallized using acetone as the antisolvent, with mass flow ratios near 1:1, and near saturated solutions of lactose. A higher resolution DoE was adopted for acetone and was processed using multivariate methods to obtain a crystallization diagram of lactose. The:model was used to create an optimized process to produce alpha-lactose monohydrate and predicted results agreed well with those obtained experimentally, validating the model. The solid state of lactose, induction time, and solid yield were accurately predicted.