Zhang Qi, Xia Mengyuan, Zheng Chenxuan, Yang Yinghong, Bao Junjie, Dai Wenjuan, Mei Xuefeng
Pharmaceutical Analytical & Solid-State Chemistry Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.
Pharmaceutics. 2023 Oct 20;15(10):2499. doi: 10.3390/pharmaceutics15102499.
Coenzyme Q10 (CoQ10) exists in two forms, an oxidized form and a reduced form. Ubiquinol is the fully reduced form of CoQ10. Compared to the oxidized form, ubiquinol has a much higher biological absorption and better therapeutic effect. However, ubiquinol has an important stability problem which hampers its storage and formulation. It can be easily transformed into its oxidized form-ubiquinone-even at low temperature. In this work, we designed, synthesized, and characterized a new cocrystal of ubiquinol with vitamin B3 nicotinamide (UQ-NC). Compared to the marketed ubiquinol form, the cocrystal exhibited an excellent stability, improved dissolution properties, and higher bioavailability. The cocrystal remained stable for a long period, even when stored under stressed conditions. In the dissolution experiments, the cocrystal generated 12.6 (in SIF) and 38.3 (in SGF) times greater maximum ubiquinol concentrations above that of the marketed form. In addition, in the PK studies, compared to the marketed form, the cocrystal exhibited a 2.2 times greater maximum total coenzyme Q10 concentration and a 4.5 times greater AUC than that of the marketed form.
辅酶Q10（CoQ10）以两种形式存在，即氧化形式和还原形式。泛醇是CoQ10的完全还原形式。与氧化形式相比，泛醇具有更高的生物吸收性和更好的治疗效果。然而，泛醇存在一个重要的稳定性问题，这阻碍了其储存和制剂开发。即使在低温下，它也很容易转化为其氧化形式——泛醌。在这项工作中，我们设计、合成并表征了一种泛醇与维生素B3烟酰胺的新型共晶（UQ-NC）。与市售的泛醇形式相比，该共晶表现出优异的稳定性、改善的溶解性能和更高的生物利用度。即使在应激条件下储存，该共晶也能长期保持稳定。在溶出实验中，该共晶产生的最大泛醇浓度比市售形式分别高12.6倍（在模拟肠液中）和38.3倍（在模拟胃液中）。此外，在药代动力学研究中，与市售形式相比，该共晶的最大辅酶Q10总浓度高2.2倍，曲线下面积高4.5倍。
