A novel co-crystal of aripiprazole (ARI), the active substance in the atypical antipsychotic Abilify, with orcinol (ORC) as a coformer, was prepared, characterized, and compared with other ARI co-crystals with dihydroxy- and trihydroxy-benzene coformers [catechol (CAT), resorcinol (RES), and phloroglucinol (PHL)] reported previously (Nanubolu, J. B.; Ravikumar, K. CrystEngComm 2016, 18, 1024–1038). Three preparation methods were used: neat grinding (NG), liquid-assisted grinding (LAG), and solvent evaporation (SE). Based on single-crystal X-ray diffraction (SC-XRD) measurements, the crystal structure of the ARI–ORC co-crystal was determined to be monoclinic. The melting point of ARI–ORC co-crystal was found to be 184–185 °C, higher than existing ARI co-crystals with multihydroxybenzene coformers. Additionally, the ARI–ORC co-crystal showed the highest dissolution rate among those in the test group in an acetonitrile–water 10/90 cosolvent. We investigated how the co-crystallization pathway and the dissolution behavior might correlate with the coformer moiety, primarily in terms of its chemical structure and melting point. Co-crystallization between ARI and PHL via grinding (NG or LAG) required the highest activation energy, mainly due to the coformer’s higher melting point. The dissolution rate of ARI co-crystals was not obviously correlated with the coformer’s melting point or its molecular weight. However, the high dissolution rate of ARI–ORC co-crystals was possibly associated with the bond angle of D–H···A for O3–H3O···N2 in the co-crystal’s superlattice structure. The stability of ARI co-crystals was examined by aging these powders in a controlled oven at 80 °C/98% relative humidity for 1 week. We observed that all of the co-crystal powders, except for the aripiprazole–catechol (ARI–CAT) pair, underwent no noticeable degradation or physicochemical change upon treatment. In conclusion, we can consider the novel ARI–ORC co-crystal as a potential drug substance with the enhanced dissolution behavior in aqueous media and good stability under stressed conditions.

中文翻译：

---

含多羟基苯化合物共成型物的阿立哌唑共晶体的制备与表征

制备，表征了一种非典型抗精神病药Abilify中的活性物质阿立哌唑（ARI）的新型共结晶，并对其进行了表征，表征，并将其与其他具有二羟基和三羟基苯共形成剂的ARI共结晶进行了比较。 [儿茶酚（CAT），间苯二酚（RES），间苯三酚和（PHL）]先前报道的（Nanubolu，JB; Ravikumar，K. CrystEngComm 2016，18，1024-1038）。使用了三种制备方法：净研磨（NG），液体辅助研磨（LAG）和溶剂蒸发（SE）。基于单晶X射线衍射（SC-XRD）测量，ARI-ORC共晶体的晶体结构被确定为单斜晶。发现ARI–ORC共晶体的熔点为184–185°C，高于现有的具有多羟基苯共形成剂的ARI共晶体。此外，在乙腈-水10/90助溶剂中，ARI-ORC共晶体在测试组中显示出最高的溶解速率。我们研究了共结晶途径和溶解行为可能如何与共形成剂部分相关，主要是在其化学结构和熔点方面。ARI和PHL之间通过研磨（NG或LAG）进行共结晶需要最高的活化能，主要是由于共成型剂的熔点较高。ARI共晶体的溶解速率与共形成剂的熔点或分子量没有明显关系。然而，ARI-ORC共晶的高溶解速率可能与超晶格结构中O3-H3O···N2与D–H···A的键角有关。通过将这些粉末在80°C / 98％相对湿度的受控烘箱中老化1周来检查ARI共晶体的稳定性。我们观察到，除阿立哌唑-邻苯二酚（ARI-CAT）对外，所有共结晶粉末在处理后均未发生明显降解或物理化学变化。总之，我们可以认为新型ARI-ORC共晶体是一种潜在的药物，在水性介质中的溶解行为增强，在压力条件下具有良好的稳定性。