Bio-Purines as Co-Formers in Resveratrol Amorphous Systems

In the organic biomineralization of guanine (GUA), amorphous GUA is utilized to enhance its solubility, facilitating its transport for the formation of biominerals, and GUA nanocrystals are employed to protect tissues from ultraviolet damage. These principles of GUA biomineralization inspire us to improve the solubility and photostability of trans-resveratrol (RES) using bio-purines, which limits its bioavailability. Bio-purines, such as GUA, hypoxanthine (HYP), and adenine (ADE), were used as co-formers in the amorphous systems of RES. Amorphous RES-2Purines with a 1:2 molar ratio were prepared via the neat ball-milling method and confirmed by powder X-ray diffraction, Raman spectroscopy, and diffuse reflectance spectroscopy. The stability, dissolution profiles, and photostability of RES-2Purines were comprehensively compared. RES-2Purines show high amorphous-to-crystalline transformation temperatures (>100 °C), confirmed by the differential scanning calorimetry-thermogravimetric analysis. Both RES-2HYP and RES-2ADE show an enhanced RES solubility (about 1.6-fold that of raw RES) in water and the simulated gastric fluid (pH 1.2). RES-2Purines can recrystallize quickly after being dispersed in water, which limits the solubility enhancements of RES-2Purines. RES-2Purines have better photostability than raw RES. Bio-purines are promising co-formers for amorphous systems to enhance the solubility and photostability of poorly water-soluble compounds.