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1996 Fiscal Year Final Research Report Summary

Analysis of Molecular Interactions in Solid Pharmaceuticals

Research Project

Project/Area Number 07672309
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
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 Research Associate, 薬学部, 助手 (40201090)
OGUCHI Toshio  Chiba University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (30169255)
NAKAJIMA Shinichiro  Yamanashi Medical University Hospital Pharmacy, Professor, 教授 (80009175)
Project Period (FY) 1995 – 1996
Keywordspharmaceutics / crystal / molecular interaction / mechanochemistry / sealed-heating / cholic acid / enantiotropic / porous
Research Abstract

Crystalline state of drugs and molecular interaction between drugs and additives in solid pharmaceutical dispersions have been investigated.
When a physical mixture of crystalline drug and cyclodextrin was heated in a glass ampoule, inclusion complex crystals were found to be formed. Since this findings, we have developed the "Sealed-Heating Method" as a new methodology for preparing cyclodextrin inclusion complex. This method have a great advantage in terms of no need of any solvent. In the present project, it was clarified through the investigations about the relationship between sealed-heating conditions and molecular behavior that the degree of crystallinity of cyclodextrin and moisture content in the system will be important factors for inclusion formation.
In the systems of dimethyl-beta-cyclodextrin with either naphthalene or 1-adamantanol, sealed-heating process provided a inclusion compound having different crystal structure from coprecipitation. It was considered that a metasta … More ble state appeared due to the non-equibrium process of crystallization.
Crystals of cholic acids were amorphised by grindig, while co-grinding with some drugs provided crystalline samples. From powder X-ray diffraction, thermal analysis and spectroscopies, cholic acids were found to form inclusion complexes with a variety of guest compound by means of co-grinding, and further effects of structure of the compounds and mixing molar ratio were clarified.
We also investigated physico-chemical change of conglomerate of optically active compounds during the process of grinding and humidifying. The ease of transformation from the conglomerate to the racemic compound was considered to be correlated to the difference of melting points between conglomerate and racemic compound and the hydrogen-bonding feature in the crystal structure.
When mixing a crystalline drug with porous materials such as porous cellulose and controlled pore glass, the drug was easily amorphisted and the chemical stability was changed. It was clarified that this resulted in the phenomena of adsorption of drug into the micro-pore of the additives through gaseous state. With regard to the mechanisms, some interesting results were obtained. Less

  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] D.Watanabe,M.Ohta,Z.J.Yaug E,Yaeinoching T.Oguchi,K.Yamamoto: "Formation of Heptakis-(2.6-cli-O-metlyl)-β-cyclodextrin-p-nitroplenol Inclusion Componvol by Sakil-Herting" Chem.Pharm.Bull. 44・4. 833-836 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Yamamoto.T.Nakao.E.Yonemochi T,Oguchi: "Tine Resolvod Fluorescent Analysis for Sealed"Heating of Dinotlyl-β-Cyclodextrin and Naththolene Syctem" J.Inclusion.Phemon.Mol.Recognit,Chem.25・1. 121-124 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Matsumoto,Y.Nakai,E.Yonemochi T.Oguchi,K.Yamamoto: "Aspirin Hydiolysis in wixtures with porous chystallice cellulose." Drug Stability. 1・2. 92-97 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Oguchi,K.Kojima,D.Watanabe E.Yonemochi,K.Yamamoto: "Preparation of Inclusion Couplexes of 1-Axamautanol with Heptokis-(2・6-dio-wetlyl)-β-cyclodextrin by Sealed-Heatirg" Yakuza : gaku. 56・2. 92-102 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] E.Yonemochi,Y.Ueno,T.Ohno e.T.guchi.S-I Nakajima,K.Yamamoto: "Evaluation of Aworphous Ursodeoxy Cholic Acid by Thormal Methods" Phara.Res.14(印刷中). (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Piyarom.E.Yonemochi T.Oguchi K.Yamamoto: "Eftects of Griuding and Humidification on Transformetion of Couglomerate to Racemic Compound in Optically Active Compowds" J.Pharmacy Pharmacology. 49(印刷中). (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Kawashima, E.Yonemochi, T.Oguchi, K.Yamamoto: "Factors Affecting the Formation in the Solid State of the Metastable Complex between Naphthalene and Dimethyl-beta-Cyclodextrin." J.Inclusion Phenom.Mol.Recognit.Chem.23. 65-72 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] D.Watanabe, M.Ohta, Z.J.Yang, E.Yonemochi, T.Oguchi, and K.Yamamoto: "Formation of a Heptakis-(2,6-di-O-methyl)-beta-Cyclodextrin-p-nitorophenol Inclusion Compound by Sealed-Heating." Chem.Pharm.Bull.44. 833-836 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Matsumoto, Y.Nakai, E.Yonemochi, T.Oguchi, and K.Yamamoto: "Aspirin Hydrolysis in Mixtures with Porous Crystalline Cellulose." Drug Stability. 1. 92-97 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Oguchi, K.Kojima, D.Watanabe, E.Yonemochi, and K.Yamamoto: "Preparation of Inclusion Complexes of 1-Adamantanol with Heptakis-(2,6-di-O-methyl)-beta-Cyclodextrin by Sealed-Heating." YAKUZAIGAKU. 56. 92-102 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Yamamoto, T.Nakao, E.Yonemochi and T.Oguchi: "Time Resolved Fluorescent Analysis for Sealed Heating of Dimethyl-beta-Cyclodextrin and Naphthalene System." J.Inclusion Phenom.Mol.Recognit.Chem.25. 121-124 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] E.Yonemochi, Y.Ueno, T.Ohmae, T.Oguchi, S.Nakajima and K.Yamamoto: "Evaluation of Amorphous Ursodeoxycholic Acid by Thermal Methods." Pharm.Res.14 (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Sujimon, E.Yonemochi, T.Oguchi and K.Yamamoto: "Effects of Grinding and Humidification on Transformation of Conglomerate to Racemic Compound in Optically Active Compounds." J.Pharm.Pharmacol.49 (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Okonogi, E.Yonemochi, T.Oguchi, S.Puttipipatkhachorn and K.Yamamoto: "Enhancement of Ursodeoxycholic Acid from the Solid Dispersion." Drug Dev.Ind.Pharm.(in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Limmatvapirat, K.Yamaguchi, E.Yonemochi, T.Oguchi and K.Yamamoto: "Deoxycholic Acid-Salicylic Acid 1 : 1 Complex." Acta Cryst.C54 (in press). (1997)

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      「研究成果報告書概要(欧文)」より

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Published: 1999-03-09  

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