Investigating Mixing Effect on Stoichiometric Ratios Diversity of Benzoic Acid-Sodium Benzoate Co-crystals
| Autor: | Tzu-Hsuan Chen, 陳子軒 |
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| Rok vydání: | 2018 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 106 Co-crystallization offers a great opportunity to enhance the physicochemical properties of drug products, such as melting point, solubility, stability, bioavailability and permeability. Our aim was to probe the mixing effect on the stoichiometry diversity of benzoic acid-sodium benzoate (HBz-NaBz) co-crystals. 8 mL of 3.36 M hydrochloric acid were fed with a rate of 3.5 or 20 mL/min into the agitated tank having the agitation rate of 75 or 600 rpm and reacted with 192 mL of the 1.74 M aqueous solution of sodium benzoate to form benzoic acid, and benzoic acid was then co-crystallized with sodium benzoate to give the co-crystals of HBz-NaBz. Micromixing and macromixing were contributed by the agitation rate of a propeller, and mesomixing was originated by the feeding rate of HCl(aq). The stoichiometric ratios, crystal structures, and crystal habit of solids were characterized by thermal gravimetric analysis (TGA), powder X-ray diffraction (PXRD), and optical microscopy (OM). The agitation rate and the feeding rate of HCl(aq) could influence the compositions of HBz-NaBz co-crystals. The local concentration of benzoic acid at the feeding point was decreased with the increase in the mixing intensity and the decrease in the feeding rate of HCl(aq). By contrast, the local concentration of benzoic acid at the feeding point was increased with the decrease in the mixing intensity and the increase in the feeding rate of HCl(aq). The effect of mesomixing on the compositions of HBz-NaBz co-crystals could be observed under 75 rpm. Pure Form A 2:1 co-crystals of HBz-NaBz were only obtained at 75 rpm and with a feeding rate of 3.36 M HCl(aq) of 20 mL/min at 20 min. Form B 2:1 co-crystals of HBz-NaBz were not detected at all. Finally, the solids were transformed to the mixtures of 1:1 and 2:1 co-crystals of HBz-NaBz at 75 rpm or 600 rpm and the feeding rate of 3.36 M HCl(aq) of 3.5 or 20 ml/min if given a long enough time. In addition, the extreme conditions for the agitation rate of propeller and the feeding rate of HCl(aq) were carried out. Pure 1:1 co-crystals of HBz-NaBz were obtained at 600 rpm and 0.4 mL/min with a feeding rate of 3.36 M HCl(aq) of 0.4 mL/min at 10 min. Agitation rate had also influenced the particle size distribution (PSD), and the PSD decreased under a high agitation rate due to crystal attrition and breakage. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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