The Design of natural deep eutectic solvent for the extraction of Acetyl-11-Keto-β-Boswellic acid using COSMO-RS

• Leveraging COSMO-RS, potential NADES were molecularly screened. • NADES-UAE system is developed for the first time in AKBA extraction. • Quantification of AKBA in extracted samples were identified by HPLC. • Maximised AKBA yield reached 475.1 ± 1.663 µg AKBA/g. Isolation of acetyl 11-keto-β-boswellic acid (AKBA) from Boswellic Acid (BA) stands out due to its beneficial biological activities as an anti-inflammatory supplement, yet its conventional extraction methods generate toxic waste. In response to environmental concerns, the preliminary study endeavours to screen twenty-two natural deep eutectic solvents (NaDES) for the highest solubility of AKBA. This was achieved through the application of the Conductor like Screening Model (COSMO-RS), by obtaining the chemical potential, activity coefficient, hydrogen bond interaction energy, and dielectric constant at infinite dilution. Eleven NaDES that were formed by organic acids, carboxylic acids, acid salts and sugar alcohols were found to be the most suitable solvents for extraction. After COSMO-RS screening, the eleven NaDES with high AKBA solubility were synthesized to reach eutectic point, with only proline – glutamic acid at molar ratios of 1:1 and 2:1 not inducing clear homogenous mixtures. Ultrasound assisted extraction were conducted by varying NaDES concentration, liquid to solid ratio (LSR) and sonication time. The composition of AKBA in the BA was determined using liquid chromatography. However, results obtained from the actual experiment showed deviations from the simulated results by COSMO-RS. The discrepancies primarily attributed to factors such as variations in physical conditions during experimentation and simplifications made in the computational model. Amongst the selected NaDES, proline: levulinic acid (1:2) performed better by achieving maximum AKBA yield (475.1 ± 1.663 µg AKBA/g); surpassing the predicted value of 383 µg AKBA/g at 70 % NaDES concentration, LSR (liquid to solid ratio) of 50:1 and sonication time of 180 min. While COSMO-RS simulations exhibited some discrepancies with experimental results, this study lays the foundation for a sustainable and efficient method for AKBA extraction, with potential applications in the pharmaceutical industry.