An Effective Cocrystal Strategy for Alleviating Urea Decomposition

Urea, renowned for its exceptional moisturizing capabilities, finds extensive application in pharmaceuticals and cosmetic products. However, its gradual decomposition in aqueous formulations poses a limitation to its broader utilization. This study introduces an effective cocrystal strategy designed to mitigate urea’s decomposition. Through computational chemistry, we simulated cocrystal systems of anhydrous citric acid with urea at various molar ratios and identified the most stable combination. The formation of the cocrystal with the mole ratio of citric acid and urea as 1 : 2, was subsequently confirmed using nuclear magnetic resonance (NMR) and X-ray diffraction (XRD) techniques. High-temperature accelerated degradation tests revealed that the decomposition rate of urea was reduced by over 10% when complexed with citric acid, thus validating the efficacy of the cocrystal approach. To ascertain that the cocrystallization process does not compromise urea’s moisturizing efficacy, we conducted hyaluronidase inhibition assays. The findings indicated that there was no significant variation in the hyaluronidase inhibition rate before and after cocrystal formation, thereby affirming the preservation of urea’s moisturizing properties throughout the process.