Antisolvent Crystallization using a Fluidic Oscillator: Modeling and Validation

There is increasing interest in developing new fluidic devices with and without moving parts for crystallization. The goal is to gain better control of particle size distribution of produced crystals. Recently, the feasibility of using a planar fluidic oscillator for crystallization was demonstrated by Pandit and Ranade (Pandit, A. V.; Ranade, V. V. Fluidic Oscillator as a Continuous Crystallizer: Feasibility Evaluation. Ind. Eng. Chem. Res. 2020, 59 (9), 3996–4006). A novel “loop setup” using a fluidic oscillator was used for carrying out seeded antisolvent crystallization of paracetamol in a methanol–water system. Because of the novel mode of operation, the conventional models are not directly applicable for interpreting the reported data on the influence of key operating parameters such as residence time, supersaturation ratio, and seed particle size distribution (PSD). In this study, a rigorous mathematical model was developed to simulate the antisolvent crystallization experiments of Pandit and Ranade. A generalized multistage model comprising mass balances, population balances, and crystallization kinetics was developed. A population balance model (PBM) was formulated in terms of the standard method of moments (MOM). A predefined log-normal distribution function with moment-based parameters (mean, μ, and variance, σ²) was used to predict PSD. The model was used to fit relevant kinetic parameters using the experimental data reported by Pandit and Ranade. A new parameter characterizing the effectiveness of mixing in the fluidic oscillator is defined. An empirical relation between this mixing parameter and other parameters is proposed. The developed model and results will be useful for extending applications of the fluidic oscillator and other fluidic devices for antisolvent crystallization.