Simultaneously Improving the Physicochemical Properties, Dissolution Performance, and Bioavailability of Apigenin and Daidzein by Co-Crystallization With Theophylline

摘要: Co-crystals have received increasing attention during the past decades for their ability to modify solubility and other physicochemical properties of active pharmaceutical ingredients. Apigenin (Agn) Daidzein (Dai) are flavonoid compounds with a variety biological effects. However, bioavailability clinical applications usually limited by poor aqueous solubilities. In this study, theophylline (Thp) is used as coformer co-crystallize Agn Dai. The solid-state co-crystals Thp Dai characterized powder X-ray diffraction, thermogravimetric analysis, differential scanning calorimetry, Raman spectroscopy, nuclear magnetic resonance experiments. addition, both show greater resistance hydration than alone. solubilities, intrinsic dissolution rates, permeabilities Agn-Thp co-crystal Dai-Thp improved compared those parent flavonoids. pharmacokinetic study shows that bioavailabilities enhanced in comparison corresponding physical mixtures This demonstrates co-crystallization using promising strategy improve compounds.