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Salt Cocrystal of Diclofenac Sodium-L-Proline: Structural, Pseudopolymorphism, and Pharmaceutics Performance Study.
Pharmaceutics ( IF 5.4 ) Pub Date : 2020-07-21 , DOI: 10.3390/pharmaceutics12070690
Ilma Nugrahani 1 , Rizka A Kumalasari 1 , Winni N Auli 1 , Ayano Horikawa 2 , Hidehiro Uekusa 2
Affiliation  

Previously, we have reported on a zwitterionic cocrystal of diclofenac acid and L-proline. However, the solubility of this multicomponent crystal was still lower than that of diclofenac sodium salt. Therefore, this study aimed to observe whether a multicomponent crystal could be produced from diclofenac sodium hydrate with the same coformer, L-proline, which was expected to improve the pharmaceutics performance. Methods involved screening, solid phase characterization, structure determination, stability, and in vitro pharmaceutical performance tests. First, a phase diagram screen was carried out to identify the molar ratio of the multicomponent crystal formation. Next, the single crystals were prepared by slow evaporation under two conditions, which yielded two forms: one was a rod-shape and the second was a flat-square form. The characterization by infrared spectroscopy, thermal analysis, and diffractometry confirmed the formation of the new phases. Finally, structural determination using single crystal X-ray diffraction analysis solved the new salt cocrystals as a stable diclofenac–sodium–proline–water (1:1:1:4) named NDPT (natrium diclofenac proline tetrahydrate), and unstable diclofenac–sodium–proline–water (1:1:1:1), named NDPM (natrium diclofenac proline monohydrate). The solubility and dissolution rate of these multicomponent crystals were superior to those of diclofenac sodium alone. The experimental results that this salt cocrystal is suitable for further development.

中文翻译:

双氯芬酸钠-L-脯氨酸的盐共晶体:结构,假多态性和药物性能研究。

以前,我们曾报道过双氯芬酸和L-脯氨酸的两性离子共晶体。但是,该多组分晶体的溶解度仍低于双氯芬酸钠盐的溶解度。因此,本研究旨在观察是否可以从双氯芬酸钠水合物中使用相同的辅酶L-脯氨酸来生产多组分晶体,从而有望改善药物性能。方法包括筛选,固相表征,结构确定,稳定性和体外药物性能测试。首先,进行相图筛查以确定多组分晶体形成的摩尔比。接下来,通过在两种条件下缓慢蒸发制备单晶,产生两种形式:一种是棒状,第二种是平方形。通过红外光谱,热分析和衍射法进行的表征证实了新相的形成。最后,使用单晶X射线衍射分析确定结构,将新的盐共晶体解析为稳定的双氯芬酸-钠-脯氨酸-水(1:1:1:4),命名为NDPT(二氯双氯芬酸脯氨酸钠四水合物)和不稳定的双氯芬酸-钠-脯氨酸-水(1:1:1:1),命名为NDPM(双氯芬酸钠脯氨酸一水合物)。这些多组分晶体的溶解度和溶解速率优于单独的双氯芬酸钠。实验结果表明该盐共晶适合进一步开发。使用单晶X射线衍射分析进行结构确定,将新的盐共晶体解析为稳定的双氯芬酸钠-脯氨酸-水(1:1:1:4),命名为NDPT(四水合双氯芬酸钠脯氨酸)和不稳定的双氯芬酸-钠脯氨酸–水(1:1:1:1),命名为NDPM(双氯芬酸钠脯氨酸一水合物)。这些多组分晶体的溶解度和溶解速率优于单独的双氯芬酸钠。实验结果表明该盐共晶体适合进一步开发。使用单晶X射线衍射分析进行结构确定,将新的盐共晶体解析为稳定的双氯芬酸-钠-脯氨酸-水(1:1:1:4),称为NDPT(四水合双氯芬酸脯氨酸)和不稳定的双氯芬酸-钠-脯氨酸–水(1:1:1:1),命名为NDPM(双氯芬酸钠脯氨酸一水合物)。这些多组分晶体的溶解度和溶解速率优于单独的双氯芬酸钠。实验结果表明该盐共晶适合进一步开发。这些多组分晶体的溶解度和溶解速率优于单独的双氯芬酸钠。实验结果表明该盐共晶适合进一步开发。这些多组分晶体的溶解度和溶解速率优于单独的双氯芬酸钠。实验结果表明该盐共晶适合进一步开发。
更新日期:2020-07-21
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