Continuous Sonocrystallization\nProcess for Controlling\nthe Polymorphs and Particle Size of Perampanel

Sonocrystallization\nis a promising technology for improving the\nreproducibility and productivity of the crystallization process because\nof the unique cavitation effect of ultrasound as well as for controlling\ncrystal polymorphs and particle size. Despite these advantages, the\nuse of ultrasound for crystallization has typically been limited to\nlaboratory studies and has not been widely adopted on an industrial\nscale by the pharmaceutical industry. In this study, ultrasound was\ncombined with continuous crystallization using a mixed-suspension,\nmixed-product removal (MSMPR) crystallizer, and this technology was\napplied to the crystallization of perampanel, demonstrating the effects\nof ultrasound and its practicality. Finally, the continuous sonocrystallization\nprocess was successfully scaled up using a 10 L ultrasonic crystallizer\ncapable of direct ultrasound irradiation, providing a methodology\nfor the scale-up of the continuous sonocrystallization process.