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Design of drug amorphous nanosuspension to achieve a pharmaceutical formulation of poorly water-soluble drug

Research Project

Project/Area Number 18K06592
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
Research InstitutionChiba University

Principal Investigator

Higashi Kenjirou  千葉大学, 大学院薬学研究院, 准教授 (40451760)

Co-Investigator(Kenkyū-buntansha) 植田 圭祐  千葉大学, 大学院薬学研究院, 助教 (40755972)
森部 久仁一  千葉大学, 大学院薬学研究院, 教授 (50266350)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords非晶質ナノ粒子 / Cryo-TEM / suspended-state NMR / 溶解性改善 / 非晶質固体分散体 / 固液界面 / 難水溶性薬物 / 界面活性剤 / 安定化 / 固体NMR / 安定性 / 分子間相互作用 / 湿式粉砕 / STEM-EDX / 表面エネルギー / 溶解性 / cryo-TEM
Outline of Final Research Achievements

Amorphous nanoparticles attract much attentions as a method for dramatically improving the solubility of poorly water-soluble drugs. However, amorphous nanosuspensions are not easy to prepare and the analytical methods to evaluate their structure and molecular state has not been established. In this study, we succeeded in preparing three types of amorphous nanosuspensions using the anti-solvent method, the wet grinding method, and the amorphous solid dispersion. Furthermore, by applying the advanced microscopy and spectroscopy techniques, the structure and molecular state of the obtained amorphous nanosuspensions were evaluated, and the formation and stabilization mechanism was analyzed precisely.

Academic Significance and Societal Importance of the Research Achievements

近年開発されている医薬品候補化合物の70%~90%は難水溶性であり、溶解性を改善する製剤技術が切望されている。本研究で得られた知見は、溶解性改善手法として期待されている非晶質ナノ懸濁液の形成・安定化メカニズムに新しい知見を与えるものである。今後益々求められていく非晶質ナノ懸濁液製剤の開発において本研究が新しい指針となり、高品質の医薬品製剤の創生に役立つものと期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (24 results)

All 2021 2020 2019 2018

All Journal Article (4 results) (of which Peer Reviewed: 2 results) Presentation (16 results) (of which Int'l Joint Research: 5 results,  Invited: 8 results) Book (4 results)

  • [Journal Article] 固体NMRによる医薬品原薬・製剤の評価2021

    • Author(s)
      東 顕二郎
    • Journal Title

      Pharm Stage

      Volume: 20(10) Pages: 59-64

    • NAID

      40022464832

    • Related Report
      2020 Annual Research Report
  • [Journal Article] 固体NMRの原薬・製剤評価への応用2020

    • Author(s)
      東 顕二郎
    • Journal Title

      Farumashia

      Volume: 56 Issue: 8 Pages: 739-743

    • DOI

      10.14894/faruawpsj.56.8_739

    • NAID

      130007883599

    • ISSN
      0014-8601, 2189-7026
    • Related Report
      2020 Annual Research Report
  • [Journal Article] Cryo-TEM and AFM Observation of the Time-Dependent Evolution of Amorphous Probucol Nanoparticles Formed by the Aqueous Dispersion of Ternary Solid Dispersions.2019

    • Author(s)
      Zhao Z, Katai H, Higashi K, Ueda K, Kawakami K, Moribe K
    • Journal Title

      Mol Pharm

      Volume: 印刷中 Issue: 5 Pages: 2184-2198

    • DOI

      10.1021/acs.molpharmaceut.9b00158

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Morphological and physicochemical evaluation of two distinct glibenclamide/hypromellose amorphous nanoparticles prepared by the antisolvent method.2018

    • Author(s)
      Yonashiro, H., Higashi, K., Morikawa, C., Ueda, K., Itoh, T., Ito, M., Masu, H., Noguchi, S., Moribe, K.
    • Journal Title

      Molecular Pharamceutics

      Volume: 15(4) Issue: 4 Pages: 1587-1597

    • DOI

      10.1021/acs.molpharmaceut.7b01122

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 固体NMRの原薬・製剤評価への応用2021

    • Author(s)
      東 顕二郎
    • Organizer
      情報機構WEBセミナー
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 固体NMRによる薬物溶解性を改善する特殊製剤の評価2020

    • Author(s)
      東 顕二郎
    • Organizer
      第64回日本薬学会関東支部大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 調製条件がglibenclamide非晶質ナノ粒子の物理的安定性に及ぼす影響2020

    • Author(s)
      東 顕二郎、森川  千佳子、植田 圭祐、森部 久仁一
    • Organizer
      日本薬学会第140年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Effect of surfactant in ternary solid dispersion on the formation of amorphous probucol nanoparticles by aqueous dispersion2019

    • Author(s)
      Zhao, Z., Ueda, K., Higashi, K., Moribe, K.
    • Organizer
      The 3rd Workshop for Japan-Korea Young Scientists on Pharmaceutics
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Preparation of amorphous nanoparticles for drugs with mid-molecular weight by wet bead milling and its characterization2019

    • Author(s)
      Chen, Z., Ueda, K., Higashi, K., Moribe, K.
    • Organizer
      The 3rd Workshop for Japan-Korea Young Scientists on Pharmaceutics
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Effect of molecular state of ternary solid dispersion on the physical property and stability of amorphous drug nanoparticles formed by aqueous dispersion2019

    • Author(s)
      Zhao, Z., Katai, H., Ueda, K., Higashi, K., Moribe, K.
    • Organizer
      The 1st Pharmaceutial Sciences Asia Conference 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Preformulation study to enhance the drug solubility based on solid state NMR methodology2019

    • Author(s)
      Higashi, K.
    • Organizer
      2019 International Conference of the KSPST
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 医薬品ナノ粒子製剤の設計とその構造解析2019

    • Author(s)
      東 顕二郎
    • Organizer
      第25回創剤フォーラム若手研究会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 固体NMRによる薬物溶解性改善製剤の分子状態評価2019

    • Author(s)
      東 顕二郎
    • Organizer
      製剤機械技術学会第29回大会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] NMRによる難水溶性薬物の溶解性を改善する特殊製剤の構造評価2019

    • Author(s)
      東 顕二郎
    • Organizer
      高分子学会19-2 NMR研究会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Preparation of cholesteryl oleate/g-cyclodextrin nanoparticles by solvent diffusion method2018

    • Author(s)
      Ishimoto, A., Ueda, K., Higashi, K., Sasako, H., Koyama, K., Moribe, K.
    • Organizer
      The 19th International Cyclodextrin Symposium
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Formation mechanism of drug nanoparticles obtained by aqueous dispersion of amorphous solid dispersion.2018

    • Author(s)
      Higashi, K.
    • Organizer
      The 2nd Workshop for Korea-Japan Young Scientists on Pharmaceutics
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] コアシェル構造を有するオレイン酸コレステリル/g-シクロデキストリンナノ粒子の調製2018

    • Author(s)
      石本 有沙, 植田 圭祐, 笹子 浩史, 東 顕二郎, 神山 和夫, 森部 久仁一
    • Organizer
      第35回シクロデキストリンシンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] Effect of preparation method of ternary solid dispersion on the evolution of amorphous probucol nanoparticles formed after aqueous dispersion2018

    • Author(s)
      Zhijing Zhao, Hiroaki Katai, Keisuke Ueda, Kenjirou Higashi, Kunikazu Moribe
    • Organizer
      製剤機械技術学会第28回大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Molecular-level understanding of stabilization mechanism of amorphous cyclosporin A nanosuspension prepared by wet bead milling with Pluronic F1272018

    • Author(s)
      Ziqiao Chen, Keisuke Ueda, Kenjirou Higashi, Kunikazu Moribe
    • Organizer
      第35回製剤と粒子設計シンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] 医薬品製剤開発におけるNMRの応用 :非晶質・ナノ製剤の評価を中心として2018

    • Author(s)
      東 顕二郎
    • Organizer
      JEOL RESONANCE NMR ユーザーズミーティング
    • Related Report
      2018 Research-status Report
    • Invited
  • [Book] ナノ・マイクロ微粒子の分散評価技術 核磁気共鳴(分担)2020

    • Author(s)
      東 顕二郎、植田 圭祐、森部 久仁一 (分担)
    • Total Pages
      227
    • Publisher
      シーエムシー出版
    • ISBN
      9784781314907
    • Related Report
      2019 Research-status Report
  • [Book] 固体医薬品の物性評価 第2版2018

    • Author(s)
      東顕二郎 分担執筆、日本薬剤学会物性FG 監修
    • Total Pages
      413
    • Publisher
      じほう
    • ISBN
      4840751072
    • Related Report
      2018 Research-status Report
  • [Book] 最新製剤学 第11版2018

    • Author(s)
      東顕二郎、分担執筆、尾関哲也、井上勝央 編集
    • Total Pages
      527
    • Publisher
      廣川書店
    • ISBN
      4567480279
    • Related Report
      2018 Research-status Report
  • [Book] 粉体の表面処理・複合化技術集大成2018

    • Author(s)
      東顕二郎、植田圭祐、森部久仁一 分担執筆、内藤 牧男 監修
    • Total Pages
      752
    • Publisher
      テクノシステム
    • ISBN
      9784924728813
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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