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Nucleation Mechanism of Organic Compound Crystals and Crystallization for Production of Nano-Medicine

Research Project

Project/Area Number 17560664
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Properties in chemical engineering process/Transfer operation/Unit operation
Research InstitutionOsaka City University

Principal Investigator

OOSHIMA Hiroshi  Osaka City University, Graduate School of Engineering, Professor, 大学院工学研究科, 教授 (20112526)

Co-Investigator(Kenkyū-buntansha) IGARASHI Koichi  Osaka City University, Graduate School of Engineering, Research Associate, 大学院工学研究科, 助手 (70315977)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥2,700,000 (Direct Cost: ¥2,700,000)
KeywordsNucleation of crystals / Crystal size distribution / Crystal polymorphs / Irradiation of microwave / Crystallization of organic compounds / Nano-medicine / Solution structure / Anti-solvent crystallization / 核発生 / 粒径制御 / マイクロ波 / 晶折 / 有機化合物の晶折 / 貧溶媒晶折 / 晶析
Research Abstract

1. In order to elucidate mechanism of crystal nucleation of organic compounds, the relationship between crystallization of polymorphs of an organic compound BPPI(C16H12C12F3N302) and the solution structure was investigated. The B02 form of BPPI crystals was precipitated from a methanol solution and the B01 form appeared from an ethanol solution. We compared crystal structures of those polymorphs with each solution structures determined by NMR analysis for solution. As a result, it was found that the conformation of BPPI molecules in each solution was similar to that of BPPI molecules forming each polymorph. The structure of molecular aggregates formed in each solution before nucleation was also similar to each crystal structure. However the structure of molecular aggregates was not completely the same as the corresponding crystal structure. This suggests that nucleation requires structure-transformation of molecular aggregates from a certain random structure to a crystal structure, namely the structure-transformation step should be the nucleation. We also obtained a result suggesting a novel concept about nucleation, that is the propagation of nucleation in solution.
2. We showed that the irradiation of microwave during crystallization suppresses nucleation even under a high super-saturation. The controlled suppression of nucleation must play an important role for production of crystals with small size and a narrow size distribution.
3. We developed a novel continuous crystallizer with a mL-scale for production of micro crystals and production of an unstable polymorph. We could operate this crystallizer at a mean residence time of sub-second without clogging of crystals.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (7 results)

All 2006

All Journal Article (5 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Crystallization of Ergosterol from Hexane Solution by a Continuous Column Crystallizer Equipped with a Water Feeding System2006

    • Author(s)
      H.Kawachi, H.Ooshima
    • Journal Title

      J. Chem. Eng. Japan 39

      Pages: 1200-1205

    • NAID

      10018401733

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Crystallization of β -Sitosterol Using a Water-Immiscible Solvent Hexane2006

    • Author(s)
      H.Kawachi, R.Tanaka, M.Hirano, K.Igarashi, H.Ooshima
    • Journal Title

      J. Chem. Eng. Japan 39

      Pages: 869-875

    • NAID

      10018206234

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Tubular Structure Agglomerates of Calcium Carbonate Crystals Formed on a Cation-Exchange Membrane2006

    • Author(s)
      M.Takiguchi, K.Igarashi, M.Azuma, H.Ooshima
    • Journal Title

      Crystal Growth and Design 6

      Pages: 1611-1614

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Flower-like Agglomerates of Calcium Carbonate Crystals on an Eggshell Membrane2006

    • Author(s)
      M.Takiguchi, K.Igarashi, M.Azuma, H.Ooshima
    • Journal Title

      Crystal Growth and Design 6

      Pages: 2754-2757

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Crystallization of β-Sitosterol Using a Water-Immiscible Solvent Hexane2006

    • Author(s)
      H.Kawachi, R.Tanaka, M.Hirano, K.Igarashi, H.Ooshima
    • Journal Title

      J. Chem. Eng. Japan 39

      Pages: 869-875

    • NAID

      10018206234

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 晶析装置および方法2006

    • Inventor(s)
      大嶋寛, 五十嵐幸一
    • Industrial Property Rights Holder
      大嶋寛
    • Industrial Property Number
      2006-229954
    • Filing Date
      2006-08-26
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 結晶化制御方法2006

    • Inventor(s)
      大嶋寛, 五十嵐幸一
    • Industrial Property Rights Holder
      大嶋寛
    • Industrial Property Number
      2006-240951
    • Filing Date
      2006-09-06
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary

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Published: 2005-04-01   Modified: 2016-04-21  

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