1992 Fiscal Year Final Research Report Summary
A Study of Mechanochemical Effects on the Solid Dispersion of Pharmaceuticals and Molecular Interactions
| Project/Area Number |
03807141
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Physical pharmacy
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| Research Institution | Chiba University |
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Principal Investigator |
YAMAMOTO Keiji Chiba University,Faculty of Pharmaceutical Sciences,Professor, 薬学部, 教授 (50110341)
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| 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)
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| Project Period (FY) |
1991 – 1992
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| Keywords | mechanochemistry / cyclodextrin / inclusion / crystallinity / molecular interaction / fluorescence / infrared spectrum / solid dispersion |
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| 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
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