Naumkina Yelizaveta, Kratochvíl Bohumil, Korotkova Elena, Čejka Jan
Department of Solid State Chemistry, University of Chemistry and Technology, Prague, Technicka 5, 16628 Prague, Czech Republic.
Chemical Engineering Department, National Research Tomsk Polytechnic University, Lenin Avenue 30, 634050 Tomsk, Russia.
Molecules. 2024 Dec 23;29(24):6060. doi: 10.3390/molecules29246060.
Apremilast (APR) is an anti-inflammatory drug commonly used in the treatment of psoriasis. In efforts to enhance its solubility, several cocrystals with similar structural features have been developed. This study investigates the cocrystallization of APR with four phenolic-type coformers: phenol, catechol, pyrogallol, and hydroxyquinol. These coformers differ in the number and position of their hydroxyl groups, with their melting points varying by as much as 100 °C. Four novel cocrystal forms were synthesized, purified, and characterized using X-Ray diffraction and thermal analysis techniques. Surprisingly, the resulting cocrystals exhibited minimal differences in their melting points. The molecular packing of APR appears to limit the network-forming potential of the hydroxyl groups, a conclusion supported by the solved crystal structures, Hirshfeld surface analysis, and differential scanning calorimetry (DSC) results.
阿普米司特（APR）是一种常用于治疗银屑病的抗炎药物。为了提高其溶解度，人们开发了几种具有相似结构特征的共晶体。本研究考察了APR与四种酚类共形成物（苯酚、邻苯二酚、连苯三酚和羟基喹啉）的共结晶情况。这些共形成物的羟基数量和位置不同，熔点相差高达100℃。通过X射线衍射和热分析技术合成、纯化并表征了四种新型共晶体形式。令人惊讶的是，所得共晶体的熔点差异极小。APR的分子堆积似乎限制了羟基形成网络的潜力，这一结论得到了解析的晶体结构、 Hirshfeld表面分析和差示扫描量热法（DSC）结果的支持。
