Ternary co-crystal, as a novel co-crystal design strategy developed on the basis of binary co-crystal, could be used to improve the physicochemical properties of active pharmaceutical ingredients (APIs) efficiently. However, it is difficult to obtain specific ternary co-crystals since such ternary one involves complex assembly of three different molecules. There are few reports on the micro-molecular structure respect of specific ternary co-crystal systems. In present work, 1:1:1 ternary co-crystal between acetazolamide (ACZ), nicotinamide (NAM) and 2-pyridone (2HP) has been synthesized successfully by mechanical grinding approach, and their structures are investigated by terahertz time-domain spectroscopy (THz-TDS) and Raman spectroscopy combined with theoretical calculation at the molecular level. The experimental THz spectral results showed that ACZ-NAM-2HP ternary co-crystal and the starting parent materials exhibited a few distinct spectral features in frequency-domain absorption spectra. Likewise, the Raman spectral result also shows some difference between the co-crystal and starting raw materials. Through density functional theory (DFT) calculations, the theoretical THz/Raman spectra and vibrational modes of two kind of possible ternary co-crystal theoretical forms (form I and II) between ACZ, NAM and 2HP were obtained. By comparing experimental and theoretical spectral results, the most suitable structure and vibrational modes of ACZ-NAM-2HP ternary co-crystal were determined. These results provide a wealth of information and unique method for studying molecular assembly and also inter-molecular interactions in specific ternary co-crystals at the molecular level in the emerging pharmaceutical co-crystal fields.

三元共晶体作为一种基于二元共晶体的新型共晶体设计策略，可用于有效提高活性药物成分（APIs）的理化性质。但是，由于特定的三元共晶体涉及三个不同分子的复杂组装，因此难以获得特定的三元共晶体。关于特定三元共晶体系的微分子结构方面的报道很少。目前工作中，通过机械研磨法成功合成了乙酰唑胺（ACZ），烟酰胺（NAM）和2-吡啶酮（2HP）之间的1：1：1三元共晶体，并通过太赫兹时域光谱研究了它们的结构。 （THz-TDS）和拉曼光谱结合分子水平的理论计算。实验的太赫兹光谱结果表明，ACZ-NAM-2HP三元共晶体和起始母体材料在频域吸收光谱中表现出一些明显的光谱特征。同样，拉曼光谱结果也显示出共晶原料和起始原料之间的某些差异。通过密度泛函理论（DFT）计算，获得了ACZ，NAM和2HP之间两种可能的三元共晶体理论形式（形式I和II）的理论THz /拉曼光谱和振动模式。通过比较实验和理论光谱结果，确定了最合适的ACZ-NAM-2HP三元共晶体的结构和振动模式。