Cocrystallization is a rational selection crystal engineering approach for the development of novel solid forms with enhanced physicochemical and mechanical properties. Nicorandil (NCR) is a niacinamide vitamin derivative used to treat angina pectoris. A binary solid form screen of NCR with homologous dicarboxylic acids afforded NCR–oxalic acid (NCR–OA, 1 : 1), NCR–fumaric acid (NCR–FA, 1 : 1), NCR–succinic acid (NCR–SA, 1 : 1), and NCR–suberic acid (NCR–SBA, 1 : 0.5). The binary solids were characterized by powder X-ray diffraction, IR and NMR spectroscopy, and DSC. NCR–FA and NCR–SBA were crystallized by slow evaporation from chloroform and toluene solvents, respectively. Single crystal X-ray diffraction confirmed that NCR–FA is a molecular salt, while NCR–SBA is a neutral cocrystal. NCR and the FA anion are connected via the robust carboxylate⋯pyridinium synthon, whereas in the NCR–SBA cocrystal, the components associate via the carboxylic acid⋯pyridine synthon. The phase stability, solubility, dissolution rate, diffusion rate and tabletability studies have demonstrated that the binary solids exhibit improved physical and mechanical properties compared to the NCR drug. Specifically, the NCR–FA salt and NCR–SBA cocrystal have higher solubility, dissolution rate, and hardness at lower pressures, making the formulation suitable for tablet compression.

中文翻译：

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通过盐和共晶形成增强尼可地尔的溶解度，渗透性和压片性

共结晶是开发具有增强的物理化学和机械性能的新型固体形式的合理选择晶体工程方法。尼古拉地尔（NCR）是用于治疗心绞痛的烟酰胺维生素衍生物。用同源二元羧酸对NCR进行二元固体形式筛选，得到NCR-草酸（NCR-OA，1：1），NCR-富马酸（NCR-FA，1：1），NCR-琥珀酸（NCR-SA，1 ：1）和NCR-硫酸（NCR-SBA，1：0.5）。通过粉末X射线衍射，IR和NMR光谱以及DSC表征二元固体。NCR-FA和NCR-SBA分别通过从氯仿和甲苯溶剂中缓慢蒸发而结晶。单晶X射线衍射证实NCR–FA是分子盐，而NCR–SBA是中性共晶。NCR和FA阴离子连接通过坚固的羧酸⋯吡啶鎓合成子，而在NCR-SBA共晶体中，各组分通过羧酸⋯吡啶合成子缔合。相稳定性，溶解度，溶解速率，扩散速率和可压片性研究表明，与NCR药物相比，二元固体具有改善的物理和机械性能。特别是，NCR–FA盐和NCR–SBA共结晶在较低压力下具有较高的溶解度，溶解速率和硬度，从而使该制剂适合压片。