Ultrasound‐assisted cooling crystallization of edaravone for improving the crystal characteristics

Abstract The crystallization of edarvone, an active pharmaceutical ingredient (API), was improved utilizing an ultrasound reactor focusing on understanding the effect of different operating parameters on the yield, particle size distribution, and shape of crystals. The best operating conditions for maximum intensification benefits of using ultrasound were elucidated as 100 W ultrasonic power, 60% duty cycle, and 35 min as sonication time. Use of ultrasound resulted in significant increase in the yield to 81.34% compared to only 35% yield using conventional reactor, under otherwise similar conditions. Particle size analysis also indicated improved particle size distribution with values of D10, D50, and D90 as 3.971, 9.642, and 15.84 μm using ultrasonic reactor whereas in the case of conventional approach, the obtained values were 21.37, 85.94, and 172.7 μm, respectively. It was also observed that the shape of crystal is rod with sharp edges using conventional approach while plate shaped with smooth edges was the observed morphology when operated with ultrasonic reactor. The elucidated findings highlight the potential of crystallization process using ultrasonic reactor as a powerful tool for refining the crystallization process and adapting drug crystal characteristics to specific formulation requirements.