The synergistic anti-tumor effect of a typical chemotherapy drug, 5-fluorouracil, and a natural flavonoid compound, kaempferol, has been reported recently. However, the oral absorption of 5-fluorouracil is incomplete and nonuniform for different individuals due to fast metabolism and an obvious peak-valley phenomenon, while kaempferol has very poor solubility and this consequently leads to low oral bioavailability. The weakness of each drug greatly restricts the potential of anti-tumor drug combination in the clinical application. In this work, a new 1 : 1 drug–drug cocrystal of 5-fluorouracil and kaempferol was successfully prepared by liquid assisted grinding, slurry conversion crystallization and evaporation crystallization. A ternary phase diagram was constructed to gain some insights into the thermodynamics of the cocrystal system. The obtained cocrystal was comprehensively characterized by single crystal and powder X-ray diffraction, differential scanning calorimetry and thermogravimetric analysis, as well as Fourier transform infrared and nuclear magnetic resonance spectroscopy. The drug–drug cocrystal enhances the stability of kaempferol and optimizes the dissolution behavior of each single component as compared to pristine drugs. Therefore, the 5-fluorouracil–kaempferol cocrystal has the potential to be developed as efficient oral formulations for drug combination which will overcome the weaknesses of each parent drug.

中文翻译：

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5-氟尿嘧啶-山奈酚药物-药物共晶体：三元相图，表征和性质评估

最近已经报道了典型的化学疗法药物5-氟尿嘧啶和天然类黄酮化合物山奈酚的协同抗肿瘤作用。然而，由于快速代谢和明显的峰谷现象，不同个体的5-氟尿嘧啶口服吸收不完全且不均匀，而山ka酚的溶解度非常差，因此导致口服生物利用度低。每种药物的弱点极大地限制了抗肿瘤药物组合在临床应用中的潜力。在这项工作中，通过液体辅助研磨，浆液转化结晶和蒸发结晶成功地制备了新的5-氟尿嘧啶和山奈酚的1：1药物-药物共晶体。构造了三元相图，以获取对共晶体系热力学的一些了解。通过单晶和粉末X射线衍射，差示扫描量热法和热重分析，以及傅立叶变换红外和核磁共振波谱对获得的共晶体进行了全面表征。与原始药物相比，药物-药物共晶体增强了山enhance酚的稳定性并优化了每个单一成分的溶解行为。因此，5-氟尿嘧啶-山奈酚共晶体有可能被开发为有效的药物联合口服制剂，从而克服每种母体药物的弱点。与原始药物相比，药物-药物共晶体增强了山enhance酚的稳定性并优化了每个单一成分的溶解行为。因此，5-氟尿嘧啶-山奈酚共晶体有可能被开发为药物联合有效的口服制剂，它将克服每种母体药物的弱点。与原始药物相比，药物-药物共晶体增强了山enhance酚的稳定性并优化了每个单一成分的溶解行为。因此，5-氟尿嘧啶-山奈酚共晶体有可能被开发为有效的药物联合口服制剂，从而克服每种母体药物的弱点。