Continuous Sonocrystallization Process for Controlling the Polymorphs and Particle Size of Perampanel

Abstract

Sonocrystallization is a promising technology for improving the reproducibility and productivity of the crystallization process because of the unique cavitation effect of ultrasound as well as for controlling crystal polymorphs and particle size. Despite these advantages, the use of ultrasound for crystallization has typically been limited to laboratory studies and has not been widely adopted on an industrial scale by the pharmaceutical industry. In this study, ultrasound was combined with continuous crystallization using a mixed-suspension, mixed-product removal (MSMPR) crystallizer, and this technology was applied to the crystallization of perampanel, demonstrating the effects of ultrasound and its practicality. Finally, the continuous sonocrystallization process was successfully scaled up using a 10 L ultrasonic crystallizer capable of direct ultrasound irradiation, providing a methodology for the scale-up of the continuous sonocrystallization process.