Continuous Antisolvent Crystallization Using Fluidic Devices: Fluidic Oscillator, Helical Coil, and Coiled Flow Inverter

Fluidic devices without moving parts are gaining more attention for continuous crystallization as they offer better mixing and number-up/scale-up possibilities. In this study, a loop setup with various combinations of devices, such as a fluidic oscillator, helical coils, and coiled flow inverters, was designed as a continuous crystallizer for seeded antisolvent crystallization of paracetamol in a methanol-water system. Care was taken to avoid particle settling and clogging while providing adequate residence time in the devices under consideration. The particle size distribution (PSD) of produced crystals was measured by offline imaging method using microscopy. The influence of fluidic device configurations, mode of operation, and residence time/batch time on the PSD of paracetamol crystals was investigated. A population balance model (PBM) was developed to interpret experimentally the observed PSD. The standard method of moments and lognormal distribution function with moment-based parameters (σ and μ) were used for simulating the evolution of PSD. Fitted kinetic parameters and developed PBM were able to simulate PSD over a wide operating range. The setup, approach, and model presented in this paper will be useful for understanding and designing continuous antisolvent crystallization using fluidic devices.