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A Study of Mechanochemical Effects on the Solid Dispersion of Pharmaceuticals and Molecular Interactions

Research Project

Project/Area Number 03807141
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Physical pharmacy
Research InstitutionChiba University

Principal Investigator

YAMAMOTO Keiji  Chiba University,Faculty of Pharmaceutical Sciences,Professor, 薬学部, 教授 (50110341)

Co-Investigator(Kenkyū-buntansha) YONEMOCHI Etsuo  Chiba University,Faculty of Pharmaceutical Sciences,Research Associate, 薬学部, 助手 (40201090)
OGUCHI Toshio  Chiba University,Faculty of Pharmaceutical Sciences,Lecturer, 薬学部, 講師 (30169255)
Project Period (FY) 1991 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1992: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1991: ¥1,100,000 (Direct Cost: ¥1,100,000)
Keywordsmechanochemistry / cyclodextrin / inclusion / crystallinity / molecular interaction / fluorescence / infrared spectrum / solid dispersion / メカノケミストリ- / 非晶質 / 包接化合物
Research Abstract

Mechanochemical effects have been investigated on the molecular states of drugs and the molecular interactions between drug and additives,e.g.cyclodextrins,microcrystalline cellulose,etc.
(1)We have reported Sealed-Heating as a novel method for preparing cyclodextrin inclusion compound. Thermal analysis,powder X-ray diffractometry and IR spectrometry were carried out to clarify the mechanism of inclusion formation between drug and cyclodextrin during the process of sealed-heating. The most important step was considered to be the transformation of cyclodextrin crystal structure,hence the binding molar ratio of drug to cyclodextrin could be enhanced by means of grinding cyclodextrin crystals before sealed-heating.
(2)Fluorescence study was made to provide clearer evidences of inclusion formation between cyclodextrins and guest drugs during mechanochemical process. Fluorescence spectrometry and fluorescence lifetime measurements supplied a quantity of suggestive information for the physicoc … More hemical change of drug molecules during the process of grinding.
(3)Solubility parameters of ground samples of cefalexine were found to depend on the degree of crystallinity. The apparent solubility of the cefalexine was correlated to the solubility parameter, demonstrating the applicability of solubility parameter in pharmaceutical field.
(4)Organic solvents were used as dissolution media in the dissolution test of drug from the ground mixture with microcrystalline cellulose. The methodology seemed to be effective to characterize the hydrogen-bond network of cellulose molecules in the ground mixtures.
(5)The change in physicochemical properties of medicinals were investigated by means of thermal analysis,X-ray diffractometry,infrared and fluorescence spectrophotometry,etc.when the crystalline medicinals were stored in the presence of either florite or synthetic aluminum silicate(SAS),which had large surface areas. The adsorbing behavior and stability of medicinals were affected by the microporous structure,surface area,surface acidity of the florite and SAS.
(6)The IR carbonyl band of benzoic acid crystals was shifted to a higher frequency through compressing with di-O-methyl-beta-cyclodextrin. It was considered as a possible mechanism that the IR change arose from 'proton transfer' in the dimerized hydrogen-bonding structure of benzoic acid crystal. Less

Report

(3 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Y.NAKAI,K.YAMAMOTO,T.OGUCHI, E.YONEMOCHI,and T.Han: "New Methods for Preparing Cyclodextrin Inclusion Compounds .IV.Enhancement of Combining Molar Rstio by Using a Ground Mixture in Heptakis-(2,6-di-O-me" Chemical&Pharmaceutical Bulletin Acid.39. 1532-1535 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Keiji YAMAMOTO and Yoshinobu NAKAI: "Inclusion Compound Formation by Co-grinding of Cyclodextrin and Host Drugs." Siberian Journal of Chemistry. 5. 51-55 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] A.S.ALI,K.YAMAMOTO,A.M.El-Sayed,F.S.Habib and Y.Na: "Molecular Interaction between Benzoic Acid and Florite and Complex Formation." Chemical&Pharmaceutical Bulletin. 40. 467-471 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K.YAMAMOTO: "On the Drug Molecular States Dispersed in Cyclodextrin Matrices." Yakugaku Zasshi. 112. 161-173 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] H.EGAWA,S MAEDA,E.RONEMOCHI,T.OGUCHI,K.YAMAMOTO、an: "Solubility Parameter and Dissolution Behavior of Cefalexin Powders with Different Crystallinity." Chemical&Pharmaceutical Bulletin. 40. 819-820 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] A.S.Ali,K.YAMAMOTO,A.M.El-Sayed,F.S.Habib and Y.Na: "Molecular Behavior of Flufenamic Acid in Physical and Ground Mixtures with Florite." Chemical&Pharmaceutical Bulletin. 40. 1289-1294 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] E.YONEMOCHI,T. OGUCHI,K.YAMOTATO and Y.NAKAI: "Acceleration of Addition Reaction of Succinic Anhydrde and ρ-Nitroaniline in Synthetic Aluminium Silicate." Advanced Powder Technolpogy. (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] T.HANAWA,E.YONEMOCHI,T.OGUCHI,Y.NAKAI: "Thermal Behavior of Ground Mixtures of Heptakis(2,6-di-o-methyl)-β-cyclodextrin and Benzoic Acid." Journal of Inclusion Phenomena. (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yoshinobu Nakai, Keiji Yamamoto, Toshio Oguchi, Etsuo Yonemochi, and Takehisa Hanawa: "New Methods for Preparing Cyclodextrin Inclusion Compounds.IV.Enhancement of Combining Molar Ratio by Using a Ground Mixture in Heptakis-(2,6-di-O-methyl)-beta- cyclodextrin and Benzoic Acid." Chem. Pharm. Bull.,. 39. 1532-1535 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Keiji Yamamoto and Yoshinobu Nakai: "Inclusion Compound Formation by Co-grinding of Cyclodextrin and Host Drugs." Siberian J. Chem.5. 51-55 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Ahmed Shaker Ali, Keiji Yamamoto, Ahmed Moustafa El-Sayed,Fawzia Sayed Habib and Yoshinobu Nakai: "Molecular Interaction between Benzoic Acid and Florite and Complex Formation." Chem. Pharm. Bull.,. 40. 467-471 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Keiji Yamamoto: "On the Drug Molecular States Dispersed in Cyclodextrin Matrices." Yakugaku Zasshi. 112. 161-173 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hiroaki Egawa, Shuei Maeda, Etsuo Yonemochi, Toshio Oguchi, Keiji Yamamoto, and Yoshinobu Nakai: "Solubility Parameter and Dissolution Behavior of Cefalexin Powders with Different Crystallinity." Chem. Pharm. Bull.,. 40. 819-820 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Ahmed Shaker Ali, Keiji Yamamoto, Ahmed Moustafa El-Sayed, Fawzia Sayed Habib and Yoshinobu Nakai: "Molecular Behavior of Flufenamic Acid in Physical and Ground Mixtures with Florite." Chem. Pharm. Bull.,. 40. 1289-1294 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Keiji Yamamoto, Toshio Oguchi, Etsuo Yonemochi, and Yoshinobu Nakai: "IR Study of Drug-Mechanochemical Mixtures." Proceeding of 4th Japan-Soviet Mechanochemistry Symposium. (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Etsuo Yonemochi, Toshio Oguchi, Keiji Yamamoto and Yoshinobu Nakai: "Acceleration of the Addition Reaction of Succinic Anhydride and p-Nitroaniline in Synthetic Aluminium Silicate." Adv. Powder Tech.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Takehisa Hanawa, Etuso Yonemochi, Toshio Oguchi, Yoshinobu Nakai and Keiji Yamamoto: "Thermal Behavior of Ground Mixtures of Heptakis(2,6-di-O-methyl)-beta-cyclodextrin and Benzoic Acid." J. Inclusion Phenomena.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Y. Nakai, K. Yamamoto, T.Oguchi, E. Yonemochi, and T.Hanawa: "New Methods for Preparing Cyclodextrin Inclusion Compounds.IV.Enhancement of Combining Molar Ratio by Using a Ground Mixture in Heptakis-(2,6-di-O-methyl)-β-cyclodextrin and Benzoic Acid." Chemical & Pharmaceutical Bulletin. 39. 1532-1535 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] Keiji Yamamoto and Yoshinobu Nakai: "Inclusion Compound Formation by Co-grinding of Cyclodextrin and Host Drugs." Siberian Journal of Chemistry. 5. 51-55 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] A. S. Ali, K. Yamamoto, A. M.El-Sayed, F. S. Habib and Y.Nakai: "Molecular Interaction between Benzoic Acid and Florite and Complex Formation." Chemical & Pharmaceutical Bulletin. 40. 467-471 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] K. Yamamoto: "On the Drug Molecular States Dispersed in Cyclodextrin Matrices." Yakugaku Zasshi. 112. 161-173 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] H. Egawa, S. Maeda, E.Yonemochi, T. Oguchi, K.Yamamoto,and Y.Nakai: "Solubility Parameter and Dissolution Behavior Cefalexin Powders with Different Crystallinity." Chemical & Pharmaceutical Bulletin. 40. 819-820 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] A. S. Ali, K. Yamamoto, A. M.El-Sayed, F. S. Habib and Y.Nakai: "Molecular Behavior of Flufenamic Acid in Physical and Ground Mixtures with Florite." Chemical & Pharmaceutical Bulletin. 40. 1289-1294 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] E. Yonemochi, T. Oguchi, K.Yamamoto and Y.Nakai: "Acceleration of the Addition Reaction of Succinic Anhydride and p-Nitroaniline in Synthetic Aluminium Silicate." Advanced Powder Technology. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] T. Hanawa, E. Yonemochi, T.Oguchi, Y. Nakai and K.Yamamoto: "Thermal Behavior of Ground Mixtures of Heptakis(2,6-di-O-methyl)-β-cyclodextrin and Benzoic Acid." Journal of Inclusion Phenomena. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Keiji Yamamoto,Yoshinobu Nakai: "Inclusion compound formation by coーgrinding of cyclodextrin and host drugs" Siberian Journal of Chemistry. 51-55 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Ahmed Shaker Ali,Keiji Yamamoto,Ahmed Moustafa Elーsaid,Fawzia Sayed Habib,Yoshinobu Nakai: "Molecular interation between benzoic acidand florite and complex formation" Chemical Pharmaceutical Bulletin. 40. 467-471 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] H.Egawa,S.Maeda,E.Yonemochi,T.Oguchi,K.Yamamoto,Y.Nakai: "Solubility parameter and dissolution behavior of various cefalexin powders" Chemical Pharmaceutical Bulletin. 40. 819-820 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] 山本 恵司: "シクロデキストリン固体分散系中での医薬品分子状態の研究" 薬学雑誌. 112. 161-173 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] "Molecular behavior of flufenamic acid in the physical and ground mixtures with florite" Chemical Pharmaceutical Bulletin. 40. (1992)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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