Amorphous Lycopene-PVP K30 Dispersions Prepared by Ball Milling: Improved Solubility and Antioxidant Activity

Lycopene is a carotenoid with strong antioxidant properties, but its therapeutic potential is limited by its poor aqueous solubility. Developing formulations that enhance its solubility and stability may improve its bioavailability and effectiveness. This study aimed to prepare amorphous lycopene-PVP K30 systems via ball milling, a solvent-free and mild technique, and to evaluate their physicochemical properties, solubility, and antioxidant activity. Formulations containing 5%, 10%, and 15% lycopene (w/w) were obtained and characterized using X-ray powder diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopy. Density Functional Theory calculations were performed to gain molecular-level insights into lycopene-polymer interactions and hydrogen-bond formation. Solubility was determined by high-performance liquid chromatography, and antioxidant activity was evaluated using the DPPH radical scavenging assay. The amorphous dispersions exhibited enhanced solubility compared to crystalline lycopene, with the 10% system showing the highest initial solubility and antioxidant capacity, while the 5% formulation demonstrated superior stability over 24 h. Ball milling proved to be an efficient method for producing amorphous lycopene-PVP K30 dispersions with improved dissolution and bioactive performance. The results indicate that lycopene loadings between 5 and 10% offer the most favorable balance between solubility, stability, and antioxidant activity, supporting their potential use in pharmaceutical formulations.