## 2 Silymarin Extraction Methods: From Conventional to Novel
### Supercritical Fluid Extraction  
Supercritical Fluid Extraction (SFE) employs supercritical fluids, typically carbon dioxide, at conditions where they exhibit both liquid and gas properties, thereby enabling the extraction of materials from a variety of sources. The phase diagram for a pure component \begin{table}
\begin{tabular}{c c c c c c c} \hline \hline \multicolumn{1}{c}{**Methods**} & \multicolumn{2}{c}{**Organic Solvent**} & \multicolumn{1}{c}{**Process Time**} & \multicolumn{1}{c}{**Process Type**} & \multicolumn{1}{c}{**Conditions**} & \multicolumn{1}{c}{**Efficiency**} \\ \hline \multirow{2}{*}{Conventional} & SE & \multirow{2}{*}{Yes} & \multirow{2}{*}{hours to days} & \multirow{2}{*}{batch} & \multirow{2}{*}{up to 100 \({}^{\circ}\)C} & \multirow{2}{*}{moderate} \\  & [24] & & & & & \\ \hline \multirow{6}{*}{Innovative} & SFE & \multirow{2}{*}{no (CO\({}_{2}\))} & \multirow{2}{*}{minutes} & \multirow{2}{*}{continuous} & 31.1 \({}^{\circ}\)C, & \multirow{2}{*}{High} \\  & [25] & MAE & & & & & \\ \cline{1-1} \cline{4-6}  & [26] & & & & & \\ \cline{1-1} \cline{4-6}  & UAE & \multirow{2}{*}{no (water)} & \multirow{2}{*}{minutes} & \multirow{2}{*}{bath} & \multirow{2}{*}{20–60 \({}^{\circ}\)C} & \multirow{2}{*}{moderate} \\ \cline{1-1} \cline{4-6}  & [27] & & & & & \\ \cline{1-1} \cline{4-6}  & EAE & \multirow{2}{*}{No} & \multirow{2}{*}{hours} & \multirow{2}{*}{batch} & \multirow{2}{*}{30–50 \({}^{\circ}\)C} & \multirow{2}{*}{High} \\ \cline{1-1} \cline{4-6}  & [28] & & & & & \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Comparison of conventional and innovative methods of silymarin extraction. is illustrated in Figure 2, which depicts the regions of the phase diagram where the liquid, gas, and supercritical fluid states meet at the critical point. Supercritical carbon dioxide (SC-CO\({}_{2}\)) is a non-toxic, density-adjustable fluid with solvent behaviour analogous to that of hexane [34]. The moderate critical pressure (7.4 MPa/73.8 bar) and low critical temperature (31.1 \({}^{\circ}\)C) of SC-CO\({}_{2}\) render it an optimal candidate for biomaterial processing, offering high selectivity and eliminating the need for toxic solvents. Silychristin, silydianin, and taxifolin, three of the key flavonolignans found in silymarin, possess higher polarity compared to other components like silybin. This increased polarity enhances their interaction with polar solvents, which traditionally poses a challenge for extraction methods that utilize non-polar or weakly polar solvents. However, in the context of SFE, this polarity issue can be effectively managed by modifying the solvent's properties. While CO\({}_{2}\) is non-polar under standard conditions, introducing polar co-solvents, such as ethanol or methanol, into supercritical CO\({}_{2}\) allows for the adjustment of polarity. This modification improves the solubility of and selectivity for polar compounds like silychristin, silydianin, and taxifolin, enhancing the extraction efficiency of these constituents and contributing to the overall yield and purity of the silymarin extract [35; 36]. Moreover, the tunability of SFE allows for the optimization of extraction parameters (e.g., pressure, temperature, and co-solvent concentration) to selectively target silychristin, silydianin, and taxifolin, ensuring their stability and minimizing degradation. This advantage underscores the suitability of SFE for extracting silymarin components with varying polarities while maintaining a low environmental impact through the use of recyclable solvents. The SFE method was employed to extract silymarin from milk thistle fruits [32]. SFE enables the use of extractants under elevated pressure and temperatures beyond their boiling points. The increased temperature improves analyte diffusion through cell walls, enhances solubility in the extractant, and reduces the solvent's viscosity and surface tension.