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

Abstract

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.

Recent Progress in Antisolvent Crystallization of Pharmaceuticals with a Focus on the Membrane‐Based Technologies

“…Antisolvent crystallization offers superior control over size, morphology and polymorphism of the final crystal, as well as lower energy consumption in supersaturation control [35]. However, scaling up an antisolvent crystallization process is very difficult [36–38], as the crystal size depends on the mixing conditions and whether the antisolvent is uniformly incorporated into the solution; hence, several mixing devices have been developed such as T‐mixer, confined impinging jet, static mixer, and multi‐inlet vortex mixer, to name a few [39–41].…”

Jet Oscillations and Mixing in Fluidic Oscillators: Influence of Geometric Configuration and Scale

“…In the wall-attachment type of FOs, the Coandǎ effect is exploited to generate a self-sustaining oscillation of the jets. This type of FO has generated considerable interest from the process intensification community and has been used for a variety of multiphase processes, such as bubble generation , and liquid–liquid extraction. − FOs are also being reported for antisolvent crystallization of Paracetamol. − Apart from the process applications, FOs also find applications as flow meters, − fluidic actuators, − and flow controllers. ,− In this work, we therefore focus on wall-attachment type FOs.…”