Yanyan Huang
, Rui Yu, Siying Xia, Wenxin Yao
* , Min Xing, Yonggang Bian, Zhiwei Huang
*
Abstract
Background: Curcumin (CUR) is a natural polyphenolic compound exhibiting diverse pharmacological activities. However, its extremely low aqueous solubility and poor chemical stability severely limit its bioavailability and clinical application. Methods: Two novel cocrystals of CUR , CUR-m-hydroxybenzoic acid (CUR-MHBA) and CUR-gallic acid (CUR-GA), were prepared via slurry crystallization and characterized by Powder X-ray diffraction (PXRD) ,Differential scanning calorimetry (DSC) ,Thermogravimetric analysis (TG) , Fourier transform infrared spectroscopy (FT-IR) , and ¹H Nuclear Magnetic Resonance (1H-NMR) . Their solubility, dissolution behavior, antioxidant capacity, and antibacterial activity were systematically evaluated. Results: Saturation solubility analysis showed that CUR-MHBA and CUR-GA had higher equilibrium solubility than CUR alone, both in water and ethanol at 25°C and 37°C. Dissolution testing showed that both cocrystals exhibited similar “spring-parachute” characteristics to CUR in four different solutions (pH 1.2, 4.5, 6.8, and 7.4), with higher steady state concentrations than CUR. Moreover, CUR-MHBA and CUR-GA demonstrated enhanced antioxidant activity. Relative to CUR, their free radical scavenging capacities increased by 1.29 and 1.43-fold, 1.47 and 3.89-fold, and 1.45 and 1.47-fold using DPPH (2,2-diphenyl-1-picrylhydrazyl) ,ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) , and FRAP (Ferric Reducing Antioxidant Power) assays, respectively. Antibacterial assays against Staphylococcus aureus and Escherichia coli also revealed significantly lower minimum inhibitory concentrations (MIC) for both cocrystals compared to CUR alone. Conclusion: CUR-MHBA and CUR-GA significantly improved the solubility, dissolution, and biological activities of CUR. These results suggest that cocrystallization with bioactive polyphenolic acids is an effective approach to enhance the physicochemical properties and therapeutic potential of CUR.