Improving the Dissolution Rate and Bioavailability of Curcumin via Co-Crystallization.

Curcumin (CUR) is a natural polyphenolic compound with various pharmacological activities. Low water solubility and bioavailability limit its clinical application. In this work, to improve the bioavailability of CUR, we prepared a new co-crystal of curcumin and L-carnitine (CUR-L-CN) via liquid-assisted grinding. Both CUR and L-CN have high safe dosages and have a wide range of applications in liver protection and animal nutrition. The co-crystal was fully characterized and the crystal structure was disclosed. Dissolution experiments were conducted in simulated gastric fluids (SGF) and simulated intestinal fluids (SIF). CUR-L-CN exhibited significantly faster dissolution rates than those of pure CUR. Hirshfeld surface analysis and wettability testing indicate that CUR-L-CN has a higher affinity for water and thus exhibits faster dissolution rates. Pharmacokinetic studies were performed in rats and the results showed that compared to pure CUR, CUR-L-CN exhibited 6.3-times-higher AUC0-t and 10.7-times-higher Cmax.

The Cocrystal of Ubiquinol: Improved Stability and Bioavailability.

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.