Koji Machida*, Koichi Igarashi, Hideo Kawachi, Mai Okamoto, Shumpei Yonezawa, Yuka Morishige, Masayuki Azuma and Akira Nishiyama,
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Continuous Sonocrystallization Process for Controlling the Polymorphs and Particle Size of Perampanel
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.
期刊介绍:
The journal Organic Process Research & Development serves as a communication tool between industrial chemists and chemists working in universities and research institutes. As such, it reports original work from the broad field of industrial process chemistry but also presents academic results that are relevant, or potentially relevant, to industrial applications. Process chemistry is the science that enables the safe, environmentally benign and ultimately economical manufacturing of organic compounds that are required in larger amounts to help address the needs of society. Consequently, the Journal encompasses every aspect of organic chemistry, including all aspects of catalysis, synthetic methodology development and synthetic strategy exploration, but also includes aspects from analytical and solid-state chemistry and chemical engineering, such as work-up tools,process safety, or flow-chemistry. The goal of development and optimization of chemical reactions and processes is their transfer to a larger scale; original work describing such studies and the actual implementation on scale is highly relevant to the journal. However, studies on new developments from either industry, research institutes or academia that have not yet been demonstrated on scale, but where an industrial utility can be expected and where the study has addressed important prerequisites for a scale-up and has given confidence into the reliability and practicality of the chemistry, also serve the mission of OPR&D as a communication tool between the different contributors to the field.