Acoustic Streaming to Control the Nucleation Kinetics of Paracetamol in a Tubular Microcrystallizer

While tubular microcrystallizers offer distinct advantages over conventional crystallization setups for manipulating crystallization conditions, precisely controlling mixing, fluid shear, and therefore also the nucleation step remains a challenge. In this study, the potential of acoustic streaming as a tool to manipulate nucleation was investigated. Acoustic streaming is fluid flow as a result of the attenuation of an ultrasonic wave propagating through a viscous medium, which in the developed setup leads to the formation of reproducible and controllable rotating and counterrotating vortices (known as Rayleigh streaming). By increasing the ultrasound wave amplitude, the fluid shear within the microcrystallizer also increases. This method to precisely control the shear rate was exploited for manipulating the primary nucleation kinetics of paracetamol from an aqueous solution. Additionally, the acoustic streaming microcrystallizer was utilized as an in-line nuclei generator for continuous crystallization. By narrowing the residence time distribution in the microcrystallizer with the acoustic streaming, the variability in the number of produced crystals can be substantially decreased, thus improving the reliability and controllability of continuous microscale crystallization processes. By demonstrating nucleation control and outlooks for continuous applications, this research highlights the potential of acoustic streaming as a powerful tool to manipulate nucleation events in small scale setups.