Continuous Sonocrystallization of Acetylsalicylic Acid (ASA): Control of Crystal Size

Abstract

A continuous tubular crystallizer system with an inner diameter of 2.0 mm and an overall length of 27 m was used to generate acetylsalicylic acid seeds in situ from ethanolic solution via cooling and ultrasound irradiation and to grow the crystals in the tubing with a controlled temperature trajectory. In order to minimize the residence time distribution, air bubbles were introduced into the system to generate a segmented gas-slurry flow. The narrow residence time distribution and the tight temperature control in the small tubing due to the large surface to volume ratio resulted in relatively narrow crystal size distributions of the product. Generally, all experiments clearly demonstrated significant crystal growth for the product crystals in comparison to the seeds and yielded product masses on the g/min scale. Furthermore, it was demonstrated that the size of the product can be easily controlled via fines removal by dissolution due to rapid heating and varying the mass of seeds per mL of solution.

The Effect of Ultrasound on the Crystallisation of Paracetamol in the Presence of Structurally Similar Impurities

“…Ultrasound has been widely reported to influence the primary nucleation process accelerating nucleation kinetics, this is typically expressed in terms of reducing the induction time and MSZW [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]. Ultrasound can also increase the rate of secondary nucleation, this is manifested as a reduction on the product crystal size distribution [20,22,24,31,32,[34][35][36][37][38][39][40][41][42][43]. Ultrasound can also influence crystal growth [20,25,26,36,40,[44][45][46] although the effect on crystal growth is not as dramatic as on nucleation and arises largely from enhanced mass transfer [46] and can influence crystal morphology.…”

Continuous Suzuki—Miyaura reactions with novel Ce—Sn—Pd oxides and integrated crystallization as continuous downstream protocol

“…Continuous crystallization is a common unit operation for the purification of organic compounds because of its high efficiency, and the low capital and operational costs [15]. In addition to large-scale batch and continuous crystallizers, numerous small-scale semibatch and continuous setups with high-intensity mixers and impeller jets have been reported in literature [16]. Furthermore, particle formation in flow-through devices with inner diameters of few centimeters has been reported.…”

“…Furthermore, particle formation in flow-through devices with inner diameters of few centimeters has been reported. Our group published several studies focusing on the controlled growth of crystals by selecting precise cooling trajectories in continuous-flow crystallizers [15][16][17][18].…”

Separation units and equipment for lab-scale process development

“…Thus, an efficient particle fluidization is crucial for robust operation. Pulsating flow by piston movement (e.g., COBC) [47] and gas-liquid slug flow [95][96][97] is under discussion to facilitate particle transport in plug flow crystallization. For helically coiled tubes, there is evidence that Dean vortices enhance particle fluidization and reduce scaling of surfaces, e.g., in membrane filtration processes [100].…”