Polymorph control of pharmaceutical compounds

• Project/Area Number: 15K14942
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Physical pharmacy
• Research Institution: Osaka University
• Principal Investigator: YOSHIMURA MASASHI 大阪大学, レーザーエネルギー学研究センター, 教授 (60314382)
• Co-Investigator(Kenkyū-buntansha): 高橋 晋 八戸工業大学, 大学院工学研究科, 准教授 (30337125)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 薬剤有機分子 / アセトアミノフェン / 準安定形選択晶出 / ソノクリスタリゼーション / ポリマー誘起核発生 / 溶液媒介相転移 / クラスター溶解制御 / レーザー誘起核発生

Outline of Final Research Achievements

We have developed an original method for selective crystallization of metastable phase acetaminophen form II　by applied ultrasonic irradiation. In this research, we attempted to control the crystallinity in order to improve temporal stability of form II.　We found that crystals of form II grown at low growth rate have high transparency and fewer defects. Powder X-ray diffraction measurement reveals that form II grown at low growth rate shows higher temporal stability than seed crystals nucleated by ultrasonic irradiation. We have also developed a new method of obtaining the metastable phase form II crystals of acetaminophen. Solution-mediated phase transformation (SMPT) from trihydrate into form II is utilized to obtain form II crystals. SMPT is triggered by seeding form II crystals into a saturated solution including trihydrate crystals, which are less stable than form II crystals.

Research Products

• [Journal Article] Crystallization of acetaminophen form II by plastic-ball-assisted ultrasonic irradiation (2017)
  • Author(s): Yo. Mori, M. Maruyama, Y. Takahashi, H. Y. Yoshikawa, S. Okada, H. Adachi, S. Sugiyama, K. Takano, S. Murakami, H. Matsumura, T. Inoue, M. Yoshimura, and Yu. Mori
  • Journal Title: Applied Physics Express Volume: Vol.10, No.2 Issue: 2 Pages: 025501-025501
  • DOI: 10.7567/apex.10.025501
  • NAID: 210000135769
  • Peer Reviewed
• [Journal Article] Matastable crystal growth of acetaminophen using solution-mediated phase transformation (2016)
  • Author(s): Yo. Mori, M. Maruyama, Y. Takahashi, H. Y. Yoshikawa, S. Okada, H. Adachi, S. Sugiyama, K. Takano, S. Murakami, H. Matsumura, T. Inoue, M. Yoshimura, and Yu. Mori
  • Journal Title: Applied Physics Express Volume: Vol.10, No.1 Issue: 1 Pages: 015501-015501
  • DOI: 10.7567/apex.10.015501
  • Peer Reviewed
• [Journal Article] Selective crystallization of metastable phase of acetaminophen by ultrasonic irradiation (2015)
  • Author(s): Y. Mori, M. Maruyama, Y. Takahashi, K. Ikeda, S. Fukukita, H. Y. Yoshikawa, S. Okada, H. Adachi, S. Sugiyama, K. Takano, S. Murakami, H. Matsumura, T. Inoue, M. Yoshimura, and Y. Mori
  • Journal Title: Applied Physics Express Volume: Vol.8, No.6 Issue: 6 Pages: 065501-065501
  • DOI: 10.7567/apex.8.065501
  • NAID: 210000137563
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 溶液媒介相転移による医薬化合物アセトアミノフェンの準安定形成長（Ⅱ） (2017)
  • Author(s): 藤本吏輝, 森陽一朗, 高橋義典, 丸山美帆子, 吉川洋史, 岡田詩乃, 安達宏昭, 杉山成, 高野和文, 村上聡, 松村浩由, 井上豪, 塚本勝男, 吉村政志, 森勇介
  • Organizer: 第64回応用物理学会春季学術講演会
  • Place of Presentation: パシフィコ横浜, 神奈川
  • Year and Date: 2017-03-14
• [Presentation] Metastable crystal growth of acetaminophen using solvent-mediated phase transformation (2016)
  • Author(s): R. Fujimoto, Yo. Mori, Y. Takahashi, M. Maruyama, H. Yoshikawa, S. Okada, H. Adachi, S. Sugiyama, K. Takano, S. Murakami, H. Matsumura, T. Inoue, K. Tsukamoto, M. Yoshimura, and Yu. Mori
  • Organizer: The 5th China-Japan Symposium on Crystal Growth and Crystal Technology
  • Place of Presentation: Fuzhou, China
  • Year and Date: 2016-11-21
  • Int'l Joint Research
• [Presentation] Metastable crystal growth of acetaminophen in low supersaturated solution (2016)
  • Author(s): K. Nii, M. Maruyama, Y. Takahashi, H. Yoshikawa, S. Okada, H. Adachi, S. Sugiyama, K. Takano, S. Murakami, H. Matsumura, T. Inoue, K. Tsukamoto, M. Yoshimura, and Yu. Mori
  • Organizer: The 5th China-Japan Symposium on Crystal Growth and Crystal Technology
  • Place of Presentation: Fuzhou, China
  • Year and Date: 2016-11-21
  • Int'l Joint Research
• [Presentation] 超音波結晶化法におけるアセトアミノフェンΙΙ形結晶の経時安定性向上 (2016)
  • Author(s): 藤原慎, 森陽一朗, 高橋義典, 丸山美帆子, 吉川洋史, 岡田詩乃, 安達宏昭, 杉山成, 高野和文, 村上聡, 松村浩由, 井上豪, 吉村政志, 森勇介
  • Organizer: 第77回応用物理学会秋季学術講演会
  • Place of Presentation: 朱鷲メッセ, 新潟
  • Year and Date: 2016-09-14
• [Presentation] 溶媒媒介相転移による医薬化合物アセトアミノフェンの準安定形成長 (2016)
  • Author(s): 藤本吏輝, 森陽一朗, 高橋義典, 丸山美帆子, 吉川洋史, 岡田詩乃, 安達宏昭, 杉山成, 高野和文, 村上聡, 松村浩由, 井上豪, 吉村政志, 森勇介
  • Organizer: 第77回応用物理学会秋季学術講演会
  • Place of Presentation: 朱鷲メッセ, 新潟
  • Year and Date: 2016-09-14
• [Presentation] 徐冷法を用いた医薬化合物アセトアミノフェンの準安定形成長 (2016)
  • Author(s): 仁井滉允, 森陽一郎, 高橋義典, 丸山美帆子, 吉川洋史, 岡田詩乃, 安達宏昭, 杉山成, 高野和文, 村上聡, 松村浩由, 井上豪, 塚本勝男, 吉村政志, 森勇介
  • Organizer: 第77回応用物理学会秋季学術講演会
  • Place of Presentation: 朱鷲メッセ, 新潟
  • Year and Date: 2016-09-14
• [Presentation] Growth of acetaminophen form Ⅱ by using solven-mediated phase transformation (2016)
  • Author(s): Yo. Mori, M. Maruyama, Y. Takahashi, H. Yoshikawa, S. Okada, H. Adachi, S. Sugiyama, K. Takano, S. Murakami, H. Matsumura, T. Inoue, K. Tsukamoto, M. Yoshimura, and Yu. Mori
  • Organizer: The 18th International Conference on Crystal Growth and Epitaxy (ICCGE-18)
  • Place of Presentation: Nagoya, Aichi
  • Year and Date: 2016-08-11
  • Int'l Joint Research
• [Presentation] Temporal stability improvement of the metastable phase of acetaminophen using low supersaturated solution growth (2016)
  • Author(s): K. Nii, M. Maruyama, Y. Takahashi, H. Yoshikawa, S. Okada, H. Adachi, S. Sugiyama, K. Takano, S. Murakami, H. Matsumura, T. Inoue, K. Tsukamoto, M. Yoshimura, and Y. Mori
  • Organizer: The 18th International Conference on Crystal Growth and Epitaxy (ICCGE-18)
  • Place of Presentation: Nagoya, Aichi
  • Year and Date: 2016-08-09
  • Int'l Joint Research
• [Presentation] 溶媒媒介相転移を用いたアセトアミノフェンⅡ形の結晶化 (2016)
  • Author(s): 森陽一朗, 高橋義典, 丸山美帆子, 岡田詩乃, 安達宏昭, 吉村政志, 森勇介
  • Organizer: 日本薬剤学会第31年会
  • Place of Presentation: 長良川国際会議場, 岐阜
  • Year and Date: 2016-05-19
• [Presentation] 低過飽和育成によるアセトアミノフェンⅡ形結晶の経時安定性向上 (2016)
  • Author(s): 仁井滉允, 森陽一郎, 高橋義典, 丸山美帆子, 岡田詩乃, 安達宏昭, 吉村政志, 森勇介
  • Organizer: 日本薬剤学会第31年会
  • Place of Presentation: 長良川国際会議場, 岐阜
  • Year and Date: 2016-05-19
• [Presentation] 超音波結晶化法におけるアセトアミノフェンⅡ形結晶の経時安定性向上 (2016)
  • Author(s): 藤原慎, 森陽一朗, 高橋義典, 丸山美帆子, 岡田詩乃, 安達宏昭, 吉村政志, 森勇介
  • Organizer: 日本薬剤学会第31年会
  • Place of Presentation: 長良川国際会議場, 岐阜
  • Year and Date: 2016-05-19
• [Presentation] 超音波印加で得たアセトアミノフェンⅡ形の安定性に及ぼす過飽和度の影響 (2015)
  • Author(s): 福喜多俊, 丸山美帆子, 森陽一朗, 高橋義典, 吉川洋史, 岡田詩乃, 安達宏昭, 杉山成, 高野和文, 村上聡, 松村浩由, 井上豪, 吉村政志, 森勇介
  • Organizer: 第45回結晶成長国内会議(NCCG-45)
  • Place of Presentation: 北海道大学学術交流会館（北海道・札幌市）
  • Year and Date: 2015-10-19
• [Presentation] 医薬化合物アセトアミノフェンの結晶多形制御 (2015)
  • Author(s): 森陽一朗, 丸山美帆子, 髙橋義典, 吉川洋史, 岡田詩乃, 安達宏昭, 杉山成, 高野和文, 村上聡, 松村浩由, 井上豪, 吉村政志, 森勇介
  • Organizer: 第39回結晶成長討論会
  • Place of Presentation: 同志社びわこリトリートセンター（滋賀県・大津市）
  • Year and Date: 2015-09-24
• [Presentation] SELECTIVE CRYSTALLIZATION OF ACETAMINOPHEN POLYMORPH WITH HIGH SOLUBILITY (2015)
  • Author(s): Y. Mori, M. Maruyama, Y. Takahashi, H. Yoshikawa, S. Okada, H. Adachi, S. Sugiyama, K. Takano, S. Murakami, H. Matsumura, T. Inoue, M. Yoshimura, and Y. Mori
  • Organizer: 20th American Conference on Crystal Growth and Epitaxy (ACCGE-20)
  • Place of Presentation: Big Sky Resort（Big Sky, Montana, USA）
  • Year and Date: 2015-08-03
  • Int'l Joint Research