Supercritical CO₂ Antisolvent Fractionation of Citrus aurantium Flower Extracts: Enrichment and Characterization of...

This study investigates the valorisation of sour orange (Citrus aurantium L.) flowers using supercritical antisolvent fractionation (SAF) with CO₂ as an antisolvent. SAF was applied to selectively recover bioactive compounds from ethanolic extracts, using supercritical CO₂ to induce precipitation. Response Surface Methodology (RSM) was employed to optimize operational conditions across a pressure range of 8.7-15 MPa and CO₂ flow rates of 0.6-1.8 kg/h, at a constant temperature of 40 °C. Pressure showed a statistically significant positive effect on precipitate yield, while higher CO₂ flow rates led to reduced recovery. High-performance liquid chromatography (HPLC) analysis identified naringin (33.7%), neohesperidin (21.6%), and synephrine (9.0%) as the main components of the enriched fractions. SAF enabled the selective concentration of these compounds, supporting its application as a green separation technique. As a complementary evaluation, preliminary in silico predictions of ADMET properties and skin permeability were performed. The results indicated favourable absorption, low predicted toxicity, and limited dermal permeation for the major flavonoids. These findings are consistent with available experimental and regulatory safety data. Overall, the study demonstrates the potential of SAF as an effective green technology for the selective extraction and enrichment of high-value bioactive compounds derived from Citrus aurantium flowers, with promising applications in cosmetic, nutraceutical, and pharmaceutical formulations.