Enhanced recovery of artemisinin from Artemisia annua L. by pressurized extraction using biobased solvents

Artemisinin is a key antimalarial compound extracted from Artemisia annua L. and widely used to treat drug–resistant malaria. In this work, an integrated strategy combining predictive solvent selection with pressurized extraction using water/biobased solvent mixtures was developed for the recovery of artemisinin and its biosynthetic precursor dihydroartemisinic acid (DHAA) via accelerated solvent extraction. COSMO-RS was used to pre-screen promising solvent candidates, which were then evaluated experimentally. Among the evaluated biobased solvents, γ–valerolactone (GVL)–water mixtures showed the highest extraction performance. Process conditions were optimized using response surface methodology, yielding 8.13 ± 0.34 mg/g of artemisinin and 3.19 ± 0.03 mg/g of DHAA at 85 °C, 13 min, and 80 wt% GVL. Stability, antiplasmodial activity, and safety of the resulting extracts were evaluated without solvent removal. The extracts retained approximately 78% of their initial artemisinin content after 30 days at 30 °C and exhibited in vitro antiplasmodial activity against Plasmodium falciparum (IC 50 = 2.22 ± 0.96 ng/mL, expressed as artemisinin equivalents), comparable to pure artemisinin and dihydroartemisinin. Control experiments demonstrated negligible solvent contribution at biologically relevant dilutions, while hemolysis and cytotoxicity assays indicated a high selectivity index and wide safety margin. Overall, combining predictive solvent screening with pressurized extraction allows for rapid solvent selection and efficient recovery. The use of biobased solvents such as GVL offers the possibility of avoiding the solvent removal step in the downstream processing of the extract, although further toxicological and regulatory evaluation is necessary prior to any pharmaceutical application.