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

药物固体分散体的机械化学效应及分子相互作用研究

基本信息

批准号：
03807141
负责人：
YAMAMOTO Keiji
金额：
$ 1.15万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

项目摘要

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

机械力化学效应主要研究药物分子状态以及药物与添加剂（如环糊精、微晶纤维素等）之间的分子相互作用。(1)We已经报道了密封加热作为制备环糊精包合物的新方法。通过热分析、粉末X射线衍射、红外光谱等方法研究了密封加热过程中药物与环糊精包合的机理。环糊精晶体结构的转变是最重要的一步，因此在密封加热前研磨环糊精晶体可以提高药物与环糊精的结合摩尔比。（2）荧光光谱研究为环糊精与客体药物在机械力化学过程中形成包合物提供了更清晰的证据。荧光光谱法和荧光寿命测量提供了大量的物理信息， ...更多信息药物分子在研磨过程中的化学变化。（3）头孢氨苄研磨样品的溶解度参数与结晶度有关。将头孢氨苄的表观溶解度与溶解度参数进行了相关性分析，验证了溶解度参数在制药领域的适用性。（4）以有机溶剂为溶出介质，对微晶纤维素研磨液进行溶出度试验。该方法似乎是有效的，在地面混合物中的纤维素分子的氢键网络的特征。（5）采用热分析、X射线衍射、红外光谱和荧光光谱等方法，研究了结晶药物在大比表面积的硅酸铝（SAS）和氟铝石（Florite）存在下的理化性质变化。氟硅酸钠和SAS的微孔结构、比表面积、表面酸性等因素影响其对药物的吸附行为和稳定性。（6）苯甲酸晶体经二-O-甲基-β-环糊精压缩后，红外羰基谱带向高频移动。认为苯甲酸晶体二聚氢键结构中的“质子转移”是引起红外光谱变化的一种可能机制。少