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.

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Publication Details

Journal
Organic Process Research & Development
Published
2026-04-21
DOI
https://doi.org/10.1021/acs.oprd.5c00517
Primary Topic
Crystallization and Solubility Studies
Type
article
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Particle Size Control in Perampanel and Taurine via Continuous Crystallization Using MSMPR Sonocrystallizer: Comparison to Couette–Taylor Crystallizer

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Organic Process Research & Development
Crystallization and Solubility Studies
article

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

Koji Machida, Shumpei Yonezawa, Akira Nishiyama, Hideo Kawachi, Masayuki Azuma, Koichi Igarashi, Yuka Morishige
article en

Abstract

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.

Organic Process Research & Development
Takasago (Japan) (JP), Kaneka (Japan) (JP), Bioengineering Center (RU), Osaka Metropolitan University (JP)
Openalex Percentile: Top 10%
Crystallization and Solubility Studies
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