Particle Size Control in Perampanel and Taurine via Continuous Crystallization Using MSMPR Sonocrystallizer: Comparison to Couette–Taylor Crystallizer

Crystal size reduction is a promising strategy to enhance drug dissolution, particularly for poorly soluble drugs. We previously developed a mixed-suspension, mixed-product removal (MSMPR) crystallizer incorporating an ultrasonication unit and demonstrated its capability for crystal size control and scale-up for perampanel synthesis. In this study, we aimed to establish a robust continuous sonocrystallization process. The effects of key parameters, including residence time, slurry volume, temperature, antisolvent ratio, and ultrasonic frequency, on the crystallization of perampanel and taurine were examined. Additionally, the performance of the MSMPR sonocrystallizer was compared with that of a Couette–Taylor crystallizer, with both systems producing similar fine crystals under the optimized conditions. The MSMPR sonocrystallizer enabled the direct production of fine crystals to improve the dissolution of active pharmaceutical ingredients without subsequent milling.

• Machida K^1,2
• Kawachi H¹
• Yonezawa S¹
• Morishige Y¹
• Azuma M²
• Nishiyama A¹
• Igarashi K²

•   ¹Pharma & Supplemental Nutrition Solutions Vehicle, Pharma Business Division, Kaneka Corporation, 1-8, Miyamae-cho, Takasago-cho, Takasago, Hyogo 676-8688, Japan
• ²Department of Chemistry and Bioengineering, Graduate School of Engineering, Osaka Metropolitan University, Osaka 558-8585, Japan

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