Eutectic Mixture Approach for Enhancing Solubility, Permeability, and Bioactivity of Curcumin: Influence of Ferulic Acid and Nicotinamide as Coformers

Curcumin, the active constituents of turmeric, possess a wide range of therapeutic properties but are limited by poor aqueous solubility and low bioavailability. This study aimed to enhance the solubility and biological activities of curcumin by forming eutectic mixtures with ferulic acid and nicotinamide as coformers. The eutectic mixtures were prepared in a 1:1 molar ratio using liquid-assisted grinding and solvent evaporation methods and characterized using FTIR, DSC, and PXRD. Their physicochemical properties (solubility, stability, and permeability) and biological activities (antioxidant, anti-inflammatory, neuroprotective, antiosteoporotic, and anticancer effects) were subsequently evaluated. The mixtures, curcumin-ferulic acid (Cur-Fer) and curcumin-nicotinamide (Cur-NCM), exhibited eutectic characteristics and demonstrated significantly improved solubility and permeability. Among the tested compounds, Cur-Fer exhibited the highest enhancement, with 2.0- and 1.6-fold increases in solubility and permeability, respectively, compared to curcumin. Both Cur-Fer and Cur-NCM exhibited enhanced anticancer activity (selectivity indexes of 2.43 and 2.34, respectively, at 100 μM), improved neuroprotective effects against MPP⁺ and amyloid β-induced toxicity at 1 pM, and stronger antioxidant properties (IC₅₀ values of 22.30 ± 0.55 μM and 29.98 ± 0.29 μM, respectively). Additionally, Cur-NCM at 1 μM significantly increased alkaline phosphatase production in human osteosarcoma (MG-63) cells compared to curcumin. However, the anti-inflammatory properties of the eutectic mixtures were comparable to those of curcumin alone. In conclusion, forming eutectic mixtures with ferulic acid and nicotinamide significantly enhances the solubility, permeability, and biological activity of curcumin.