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Crystallization Diagram for Antisolvent Crystallization of Lactose: Using Design of Experiments To Investigate Continuous Mixing-Induced Supersaturation
journal contribution
posted on 2017-03-28, 00:00 authored by Pól MacFhionnghaile, Vaclav Svoboda, John McGinty, Alison Nordon, Jan SefcikThis
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 a 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 α-lactose monohydrate and β-lactose were crystallized
under most conditions with β-lactose content increasing with
increasing amount of antisolvent. Pure α-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 α-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.