| Summary: | 碩士 === 國立中央大學 === 化學工程與材料工程學系 === 105 === Co-crystal is regarded as an approach to promote the solubility of drugs and is developed rapidly in recent years. The aim of this thesis was to discuss the effects of macro-, meso-, and micro-mixing on the stoichiometry and particle size distribution of benzoic acid-sodium benzoate (HBz-NaBz) co-crystals. According to the literature, 1:1 co-crystals of HBz-NaBz was synthesized by the grinding method in methanol. The 2:1 co-crystals of HBz-NaBz of Form A was synthesized by grinding method in ethanol-water (4:1 v/v) or evaporating in ethanol, and the 2:1 co-crystals of HBz-NaBz of Form B was synthesized by evaporating in methanol. However, in this study, we used only the pure water as a solvent to obtain the co-crystals. The aqueous solution of hydrochloric acid and sodium benzoate were reacted to form benzoic acid, and benzoic acid was co-crystallized with sodium benzoate in the aqueous solution to give the co-crystals of HBz-NaBz. The stoichiometric ratios and crystal structure of the solids were characterized by thermal gravimetric analysis (TGA) and powder X-ray diffraction (PXRD). Different molar ratios of HCl and NaBz, experiment times, and concentrations were screened for the optimal operating condition. In this thesis, only 1: 1 co-crystals of HBz-NaBz and Form A of 2:1 co-crystals of HBz-NaBz were obtained. Form B of 2:1 co-crystals of HBz-NaBz was not detected. 1: 1 co-crystals of HBz-NaBz and Form B of 2:1 co-crystals of HBz-NaBz were unstable forms, and Form A of 2:1 co-crystals of HBz-NaBz was the thermodynamically stable form. In the U-tube experiments, the local concentration of benzoic acid at the feed point would influence the composition of the solids harvested at t = 0.5 h. Therefore, the local concentration of benzoic acid at the feed point was influenced by the stirring rates of the turbine and propeller and the feed rate of HCl(aq) to create the different effects of macro-, meso-, and micro-mixing to produce the different compositions of solids. However, according to Ostwald's Rule of Stages, the solids were transformed to a mixture of 1:1 and 2:1 co-crystals of HBz-NaBz at t = 4 h. According to Ostwald's ripening, all the harvested samples were given more or less the same particle size distribution (PSD) at t = 4 h. This study relates process understanding and product knowledge to the quality control of co-crystals: the stoichiometric ratio and the PSD.
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