Fluidic Oscillator as a Continuous Crystallizer: Feasibility Evaluation

Crystallization is an important separation unit operation accounting for nearly 90% of organic molecules in the pharmaceutical and fine chemical industries. Recently, continuous crystallization was demonstrated to have several advantages over the conventional batch crystallization in terms of improved product consistency, reduced labor costs/economic footprint, and better process control. Continuous stirred tank crystallizers, however, are limited in mixing/heat transfer capabilities and have issues like cyclical oscillations in product quality. Tubular crystallizers can mitigate these issues and, however, suffer from issues related to particle settling and blockages. Fluidic oscillators with one or more feedback channels are gaining popularity in recent years due to the advent of microfluidics. Jet oscillations in fluidic oscillators were shown to consistently provide vigorous mixing and heat transfer above a critical Reynold's number. In the present study, the feasibility of the fluidic oscillator as a continuous crystallizer was evaluated to mitigate challenges faced by previous continuous crystallization technologies. A novel "loop setup" was proposed for continuous crystallization and was investigated using the seeded antisolvent crystallization of paracetamol in a methanol-water system. The effects of key operating conditions of residence time, supersaturation ratio, operational mode, fluidic device, device orientation, and seed size were investigated. Throughout the study, it was observed that the loop setup gave product particle size distributions consistent with enhanced mixing behavior. Further, it was demonstrated that the proposed continuous crystallizer was better in terms of scale up in comparison with batch crystallizers. The presented results and approach will be useful to develop fluidic oscillators as a useful platform for continuous crystallization.