Graduate School of Pharmaceutical Sciences, Tokushima University, 1-78-1 Shomachi, Tokushima 770-8505, Japan.
Graduate School of Pharmaceutical Sciences, Tokushima University, 1-78-1 Shomachi, Tokushima 770-8505, Japan.
J Pharm Sci. 2017 Dec;106(12):3458-3464. doi: 10.1016/j.xphs.2017.07.025. Epub 2017 Aug 7.
We report the effects of dry mechanochemical synthesis conditions on the crystallization of caffeine (CA) and oxalic acid (OX) 2:1 cocrystal. CA anhydrate and OX dihydrate were grinded at various temperatures, rotation speeds, and grinding time. The cocrystal was also synthesized by an organic solvent evaporation method, as a reference. The produced samples were measured by a powder X-ray diffraction (PXRD) analysis. The PXRD spectra suggest that the grinded cocrystal has a lower crystallinity than the evaporated one. The diffractograms for the cocrystals synthesized by 2 kinds of methods were further evaluated by multivariate curve resolution-alternating least squares method. Sources of the mathematical models constructed were assigned to the cocrystal and unreacted mixture of CA and OX dihydrate. The present approach is concluded to be useful for the improvement of pharmaceutical property because cocrystallization is closely relating to the solubility characteristics, bioavailability, stability, and so on of drugs.
我们报告了干法机械化学合成条件对咖啡因（CA）和草酸（OX）2:1 共晶结晶的影响。CA 无水物和 OX 二水物在不同的温度、转速和研磨时间下进行研磨。共晶也通过有机溶剂蒸发法合成，作为参考。所制备的样品通过粉末 X 射线衍射（PXRD）分析进行测量。PXRD 图谱表明，研磨得到的共晶的结晶度低于蒸发得到的共晶。通过多变量曲线分辨交替最小二乘法对通过 2 种方法合成的共晶的衍射图进行了进一步评估。所构建数学模型的来源被分配给共晶和 CA 无水物与 OX 二水物的未反应混合物。本方法被认为有助于改善药物的性质，因为共晶化与药物的溶解度特性、生物利用度、稳定性等密切相关。
