| Computational Fluid Dynamics (CFD) and the Population Balance Equation (PBE) are coupled together and employed along with physical property and kinetic data to simulate antisolvent crystallization of glycine from water using ethanol as the anti-solvent. The purpose of the coupled CFD-PBE approach is to investigate nucleation and mixing quantitatively to better understand the scale-up of antisolvent crystallization.; The coupled CFD-PBE approach was validated with experiments conducted in MultiMax, Advanatage, and LabMax systems in terms of onset of nucleation and product CSDs. An examination on the moments obtained from simulations explains the experimental observation that larger crystals are generated in big vessels, indicating the importance of the early stage of crystallization processes and the homogeneity of supersaturation distributions determined by the mixing. A comparison of nucleation time and mesomixing time is proposed to better understand which of these processes is the rate limiting step at different conditions and vessel volumes.; The coupled CFD-PBE approach was applied to investigate the effect of agitation rate, antisolvent addition rate and position, seed amount, and scale of crystallizers on antisolvent crystallization processes in crystallizers bigger than 20 Liter. By comparing CFD-PBE simulation results with experimental observations reported in the literature, the CFD-PBE approach was shown to be capable of modeling the antisolvent crystallization process. Two strategies, batch time extension and multiple feeds, were employed to reduce the localized high supersaturation in a large tank of 1045 Liter by scaling up the process taking place in 21 liter either to maintain tip speed (St) or power input per unit volume (P/V). The rule of P/V offers an improved mixing compared to the rule of St, and generates small crystals with a narrow CSD.; By correlating various operating conditions with supersaturation distributions, a scale up rule to determine antisolvent addition rates is proposed to better replicate mixing and antisolvent crystallization processes upon scale up. The rule is to maintain the dimensionless parameter nfND 3/Q, where nf is the number of feeds, N agitation rate, D the diameter of crystallizers, and Q antisolvent feed rate. |
