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

已经研究了机械化学效应对药物的分子态以及药物与添加剂之间的分子相互作用，例如环氯麦克罗斯林，微晶纤维素等。（1）我们报告了作为制备环糊糖症包含化合物的新型方法。在密封加热过程中，进行热分析，粉末X射线衍射法和红外光谱法以阐明药物与环糊精之间的纳入形成机理。最重要的步骤被认为是环糊精晶体结构的转化，因此，可以通过在密封加热之前磨削环糊精晶体的方法来增强药物与环糊精的结合摩尔比。荧光光谱和荧光寿命测量值为物理学提供了大量的暗示信息……在研磨过程中，药物分子的更异质变化。（3）发现头孢菌素地面样品的溶解性参数被发现取决于结晶度。头孢再胺的明显溶解度与可溶性参数相关，证明了溶解度参数在药物领域的适用性。（4）在与微晶纤维素的地面混合物中的药物溶解测试中，将有机溶液用作溶解培养基。该方法似乎有效地表征了地面混合物中纤维素分子的氢键网络。（5）通过热分析，X射线衍射测量，红外和荧光光聚光度测定术，X射线衍射术，X射线分光光度计等。区域。药物的吸附行为和稳定性受到微孔结构，表面积，植物和SAS的表面酸度的影响。（6）苯甲酸晶体的IR羰基带被用DI-O-O-oto-methyly-beta-beta-cycledextrin通过压缩来移动到更高的频率。它被认为是一种可能的机制，即IR变化来自苯甲酸晶体的二聚氢键结构中的“质子转移”。较少的