Analysis of Molecular Interactions in Solid Pharmaceuticals

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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