Computational fluid dynamics modeling of mixing effects for crystallization in coaxial nozzles

A leading method for the crystallization of pharmaceutical compounds is to rapidly mix an antisolvent with a solvent saturated with the desired drug. Compared to cross-flow mixers, coaxial nozzles have negligible buildup of crystalline material on their surfaces and are less likely to plug. Rather than requiring moving parts, the inlet velocities of the input solvent and antisolvent streams provide the necessary mechanical energy for turbulent mixing. Computational fluid dynamics (CFD), micromixing modeling, and the population balance equation (PBE) are coupled in the simulation of coaxial nozzle crystallization of lovastatin-saturated methanol by intense mixing with the antisolvent water. The simulations show that flow rates of inlet streams have a profound effect on crystal size distribution (CSD), which is caused by different degrees of inhomogeneity in the supersaturation and nucleation and growth rates. Other important process parameters are pipe length of pipe downstream of the injection point and the inner and outer pipe diameters. To the authors' knowledge, this is the most detailed simulation study on coaxial crystallizers reported to date. The simulation results show the feasibility of tailoring a specific crystal size distribution by adjusting the operating conditions (such as inlet stream velocities) of the coaxial crystallizer. (C) 2015 Elsevier B.V. All rights reserved.