Improving Dissolution and Photostability of Vitamin K3 via Cocrystallization with Naphthoic Acids and Sulfamerazine

Menadione (MD), also known as vitamin K3, has been widely applied in fortified food, feed, and the nutrition industry for its antihemorrhagic activity. However, the poor photostability in the solid state has greatly affected its biological performance and limited its applications. With the objective to alter the topochemical photoreactivity, a cocrystallization approach was employed, and three MD cocrystals with naphthoic acids and sulfamerazine were designed and prepared. Single crystal structures were determined, and solid-state characterization were performed. Solid-state UV-vis spectra revealed a significant red-shift of UV absorption in the cocrystal solids resulting in variant color differences. These physicochemical changes may be attributed to the enhanced pi---pi interactions and change-transfer interactions within these molecular complexes. More importantly, the newly synthesized cocrystals displayed better dissolution behavior and superior photostability with respect to MD itself. No obvious degradation was observed under stressed photoirradiation conditions. These findings may provide new possibilities to the application of this key vitamin.