Optimisation of Supercritical CO2 Extraction of Phenolic Compounds from Tomato ( <i>Solanum lycopersicum</i> L.) Seeds Using Response Surface Methodology

BACKGROUND: Tomato seeds, a by-product of the tomato-processing industry, are a rich source of bioactive compounds with promising nutritional and functional potential. OBJECTIVE: This study aimed to optimize the supercritical CO2 (SC-CO2) extraction of phenolic compounds from Solanum lycopersicum L. seeds using a Full Factorial Design (FFD) within the framework of Response Surface Methodology (RSM). METHOD: The effects of extraction pressure (100-500 bar) and temperature (40-80 °C) were evaluated, with oil extraction yield and total phenolic content (TPC) as response variables. A one-factor-at-a-time (OFAT) approach assessed the effect of ethanol (0.25-1.0 mL) as a co-solvent under constant optimal extraction conditions. Derringer's desirability function was applied to identify simultaneous optimal conditions to maximize both responses. The main phenolic compounds were putatively annotated via high-performance liquid chromatography coupled with diode array detector and time-of-flight mass spectrometer (HPLC-DAD-TOF). RESULTS: Extraction pressure and co-solvent volume significantly affected both oil extraction yield and TPC, while temperature primarily influenced yield. Multi-response optimization achieved an overall desirability value of 1.0 at 425 bar and 78 °C with 1 mL ethanol, resulting the highest oil extraction yield and phenolic recovery. CONCLUSION: SC- CO2 extraction combined with desirability-based RSM is an efficient, green technique for valorizing tomato-processing residues, supporting circular bioeconomy principles through the sustainable recovery of high-value bioactives. HIGHLIGHTS: Optimized SC-CO2 extraction using RSM revealed that the factors most influencing oil extraction yield and the recovery of phenolic compounds were pressure and the quantity of co-solvents used. HPLC-DAD-TOF analysis putatively annotated the main phenolic compounds, thus emphasizing the sustainable valorization of by-products from tomato processing.