A novel dual-drug ternary salt cocrystal of piperazine ferulate (PRZ–FLA) with pyrazinamide (PRA), namely, PRZ–FLA–PRA, has been synthesized and characterized. Single-crystal X-ray diffraction reveals that the cocrystal has a formula of (PRZ²⁺)·(FLA^–)₂·(PRA)₂, in which the PRZ²⁺ and FLA^– ions form a one-dimensional chain by the strong charge-assisted hydrogen bonds and then interacts with neutral PRA molecules through hydrogen bonds, constructing a three-dimensional supramolecular network. As far as we know, this is the first example of a dual-drug ternary salt cocrystal simultaneously containing both a nephrosis-treating drug and antituberculous agent. The solubility and dissolution rate studies of the cocrystal are conducted under various physiological pH environments to assess the effects of cocrystallization on in vitro release behaviors of PRZ–FLA, and the outcomes suggest that the intrinsic dissolution rate and solubility of PRZ–FLA in the cocrystal are slowed and lowered, respectively, in comparison with the parent drug. The present work not only provides an alternative approach to reduce the release rate, which is in favor of solving issues with the short half-life of PRZ–FLA, but also offers a potential synergistic therapeutic application as a promising combination drug to treat the symptoms of complications from tuberculosis and renal injury.

中文翻译：

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吡嗪酰胺与吡嗪酰胺的缓释双药物三元盐共晶体：合成，结构和Hirshfeld表面分析

合成并表征了阿魏酸哌嗪（PRZ-FLA）与吡嗪酰胺（PRA）的新型双药三元盐共晶体。X射线单晶衍射表明，该共晶的化学式为（PRZ ²⁺）·（FLA ^–）₂ ·（PRA）₂，其中PRZ ²⁺和FLA ^–离子通过强电荷辅助的氢键形成一维链，然后通过氢键与中性PRA分子相互作用，从而构建了三维超分子网络。据我们所知，这是同时含有肾病治疗药和抗结核药的双药三元盐共晶体的第一个例子。共晶的溶解度和溶解速率研究是在各种生理pH环境下进行的，以评估共晶对PRZ-FLA体外释放行为的影响，结果表明PRZ-FLA在共晶中的固有溶解速率和溶解度与母体药物相比，分别降低和降低。目前的工作不仅提供了降低释放速率的替代方法，