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A redesigned pulmonary formulation platform: Preparation of carrier particles with advanced alveolar transportability

Research Project

Project/Area Number 21K06504
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 InstitutionOsaka Medical and Pharmaceutical University

Principal Investigator

Tozuka Yuichi  大阪医科薬科大学, 薬学部, 教授 (50312963)

Co-Investigator(Kenkyū-buntansha) 門田 和紀  大阪医科薬科大学, 薬学部, 准教授 (50709516)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords吸入粉末剤 / コンポジット粒子 / 噴霧乾燥法 / 実験計画法 / フィトグリコーゲン / マトリックス / デキストラン / 噴霧凍結乾燥法 / リファンピシン / 粒子設計 / 粒子形態制御 / 肺深部到達性
Outline of Research at the Start

肺深部到達率の極めて高いキャリア微粒子の調製のために、in silico粒子設計技術を組み合わせ、有効性の高い新たなプラットフォーム開発により、市販製剤処方をリデザインする。具体的には、以下の3つの最新アプローチを取り入れた予測精度の高い設計を行う。
(1)実験計画法による処方最適化 ⇔ データマイニングによる最適調製条件改善
(2)in silico評価による肺内部での粒子挙動解析および到達部位予測
(3)調製粒子のin vitro物性評価・形態学的評価とin silico形態学的解析

Outline of Final Research Achievements

Phytoglycogen (PyG) was used as a multi-functional additive that enhances pulmonary delivery of drugs. Dry powder inhaler (DPI) formulations of an antitubercular drug, rifampicin, were fabricated by spray drying with PyG. Extra-fine particle fraction (eFPF, the fraction of particles with aerodynamic size <2 μm) is an essential metric to evaluate the deep lung delivery of DPIs. The product of spray-drying has the potential to be applied in DPI formulations regarding its controllable size. By using a design space compiled from response surfaces, the most critical factor controlling inhalation properties was gas flow rate. The fine particle fraction of the porous particle batch reached nearly 60%, whereas in the formulation containing wrinkled carrier particles, eFPF was 25.0%. The inclusion of PyG dramatically improved the inhalation performance of porous and wrinkled powder formulations.

Academic Significance and Societal Importance of the Research Achievements

経肺投与製剤は、薬効の発現が早く、気管支喘息などの肺局所治療だけでなく、全身性疾患治療にも応用可能である。経肺投与製剤のうち、吸入粉末剤は携帯性に優れ、吸入しやすい利点を有するが、現行市販品の製剤処方による吸入粉末剤は気管支までの到達が限度であり、薬物を肺深部炎症部位に直接到達可能なキャリアの開発には至っていない。
薬物と添加剤との間でコンポジット粒子を作製する場合には、粒子径や形状などの粒子物性を制御した粒子設計が課題であり、本研究成果で得られた、医薬品―添加剤による高度肺到達性の可能性を持ったコンポジット粒子作成法は、吸入粉末剤設計の新たな可能性を示している。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (10 results)

All 2023 2022 2021

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (6 results) (of which Int'l Joint Research: 2 results) Book (1 results)

  • [Journal Article] Tuning the Phytoglycogen Size and Aggregate Structure with Solvent Quality: Influence of Water?Ethanol Mixtures Revealed by X-ray and Light Scattering Techniques2023

    • Author(s)
      Kamarainen Tero、Kadota Kazunori、Tse Jun Y.、Uchiyama Hiromasa、Oguchi Toshio、Arima-Osonoi Hiroshi、Tozuka Yuichi
    • Journal Title

      Biomacromolecules

      Volume: 24 Issue: 1 Pages: 225-237

    • DOI

      10.1021/acs.biomac.2c01093

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Modulating Pore Space Architecture of Ice-Templated Dextran Microparticles Using Molecular Weight and Concentration2022

    • Author(s)
      T. Kamarainen, K. Kadota, J. Y. Tse, H. Uchiyama, S. Yamanaka, Y. Tozuka
    • Journal Title

      Langmuir

      Volume: 38 Issue: 21 Pages: 6741-6751

    • DOI

      10.1021/acs.langmuir.2c00721

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Porous particles and novel carrier particles with enhanced penetration for efficient pulmonary delivery of antitubercular drugs2021

    • Author(s)
      Tse Jun Yee、Koike Atsushi、Kadota Kazunori、Uchiyama Hiromasa、Fujimori Ko、Tozuka Yuichi
    • Journal Title

      European Journal of Pharmaceutics and Biopharmaceutics

      Volume: 167 Pages: 116-126

    • DOI

      10.1016/j.ejpb.2021.07.017

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] Aggregation of phytoglycogen in water-ethanol mixtures characterized by small-angle X-ray scattering and dynamic light scattering measurements, The 7th International Conference on the Characterization and Control of Interfaces for High Quality Advanced Materials2022

    • Author(s)
      T. Kamarainen, K. Kadota, J.Y. Tse, H. Uchiyama, T. Oguchi, H. Arima-Osonoi, Y. Tozuka
    • Organizer
      The 7th International Conference on the Characterization and Control of Interfaces for High Quality Advanced Materials
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Ice templated dextran microparticles by spray freeze drying: Influence of molecular weight and concentration2022

    • Author(s)
      T. Kamarainen, J.Y. Tse, H. Uchiyama, K. Kadota, Y. Tozuka
    • Organizer
      粉体工学会2022年度春期研究発表会シンポジウム
    • Related Report
      2022 Research-status Report
  • [Presentation] 噴霧乾燥法による新規キャリア粒子による吸入粉末製剤の設計2022

    • Author(s)
      門田和紀、謝 晉頤、T. Kamarainen、内山博雅、戸塚裕一
    • Organizer
      粉体工学会第 56 回技術討論会
    • Related Report
      2022 Research-status Report
  • [Presentation] Image analysis routines toward pore characterization of spray freeze dried dextran microparticles2022

    • Author(s)
      T. Kamarainen, H. Uchiyama, K. Kadota, Y. Tozuka
    • Organizer
      粉体工学会第 56 回技術討論会
    • Related Report
      2022 Research-status Report
  • [Presentation] Composite spray freeze-dried particles for functional food with improved dissolution properties by enhanced water dispersibility2021

    • Author(s)
      J. Y. Tse, G. Nemoto, H. Uchiyama, K. Kadota, Y. Tozuka
    • Organizer
      8th Asian Particle Technology Symposium
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 新規キャリア粒子による肺深部への高効率な到達性を実現した抗結核薬吸入粉末剤の設計2021

    • Author(s)
      入船三奈子、謝晉頤、小池敦資、内山博雅、門田和紀、藤森功、戸塚裕一
    • Organizer
      日本薬剤学会第36年会
    • Related Report
      2021 Research-status Report
  • [Book] 医薬品におけるDDS技術と製剤開発への応用2021

    • Author(s)
      戸塚裕一、門田和紀 他多数
    • Total Pages
      401
    • Publisher
      情報機構
    • Related Report
      2021 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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