Aspen Plus®-Validated CCD–RSM Optimisation of Pressurised Ethanol/Water Extraction for Sustainable Recovery of Antioxidant and Photoprotective Constituents from Inula salicina L.

This study presents an integrated approach for producing antioxidant-rich polar fractions from Inula salicina L. via pressurised ethanol/water extraction (PLE-EtOH/H2O), optimised by coupling a central composite design and response surface methodology (CCD-RSM) with Aspen Plus® simulation. The effects of PLE temperature, extraction time, and EtOH/H2O ratio for yield, total phenolic (TPC) and flavonoid (TFC) content, and Trolox equivalent antioxidant capacity (TEAC) measured in ABTS•+-scavenging, cupric ion reducing antioxidant (CUPRAC) and oxygen radical absorbance (ORAC) assays were assessed via a multi-response optimisation approach. Optimal conditions were set at 82 °C, 27 min, and 60% EtOH (v/v), yielding ~29 g extract per 100 g plant material, characterised by high TPC (227 mg GAE/g), TFC (34 mg QE/g), and TEAC values in the CUPRAC (1473 mg TE/g), ABTS (869 mg TE/g), and ORAC assays (1165 mg TE/g). The TPC and TEAC values of the post-extraction residue were >92% lower than those of unextracted I. salicina, confirming efficient recovery of the major portion of antioxidant-active constituents by PLE-EtOH/H2O. The high in vitro radical scavenging capacity, reducing power, and photoprotective potential (sun protection factor ~50 at 0.5 mg/mL) of the I. salicina extract are consistent with its phenolic-rich composition, with chlorogenic acid (~97 mg/g extract) and its derivatives being the major constituents. The validated Aspen Plus® model closely aligned with the CCD-RSM predictions, supporting process scale-up and energy feasibility and demonstrating an industry-relevant, green-solvent PLE process for producing higher value-added I. salicina fractions with potential applications in the food, pharmaceutical, nutraceutical, and cosmetic sectors.