Analysis of Molecular Interactions in Solid Pharmaceuticals

固体药物中的分子相互作用分析

基本信息

批准号：
07672309
负责人：
YAMAMOTO Keiji
金额：
$ 1.47万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

项目摘要

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

已经研究了药物与固体药物分散体中药物与添加剂之间的晶体状态。在将晶体药物的物理混合物和环糊精的物理混合物在玻璃安培中加热后，发现成立包含复合物晶体。自从这一发现以来，我们开发了“密封加热方法”作为制备环糊精融合复合物的一种新方法。此方法在不需要任何溶解度方面具有很大的优势。在本项目中，通过调查对密封加热条件和分子行为之间的关系进行了澄清，系统中环糊精和水分含量的结晶度将是置换形成的重要因素。在二甲基-Beta-cyclodextrin的系统中，与1-二甲基或1-二氨甲醇的结构相互融合的结构，相互融合的结构相互融合。据认为，由于结晶的非等效过程，出现了一个metasta……更易碎的状态。胆汁酸的晶体被格林迪格（Grindig）无形，同时与某些药物共同汇总提供了结晶样品。从粉末X射线衍射，热分析和光谱镜中，发现胆酸通过共同环境形成具有多种客人化合物的包容性复合物，并阐明了化合物结构和混合摩尔比的进一步效果。我们还研究了在整个过程和磨砂过程中，在整个过程中，我们还调查了集体活跃化合物的物理化学变化的物理化学变化。从砾岩到外消旋化合物的易于转化与晶体结构中的融化点和氢键特征的差异相关。将结晶药物与多孔材料（如多孔纤维素纤维素和控制孔玻璃）混合在一起时，很容易变化，该药物很容易变化，并更改了化学稳定性。可以澄清的是，这导致了通过气态态将药物吸附到添加剂的微孔中的现象。关于这些机制，获得了一些有趣的结果。较少的