# Modern Techniques for Flavonoid Extraction--To Optimize or Not to Optimize?
## 4 Selection of Variables for the Optimization of Modern Techniques for Flavonoids Extraction
### Supercritical Fluids Extraction  
Supercritical fluids extraction (SFE, Figure 7a) is categorized as a new extraction process that is a more ecologically friendly way to create native compounds that have uses in many different sectors, from sustainable sources including herbs, spices, aromatic, and medicinal plants [114; 115]. This method uses supercritical fluids to isolate and remove certain bioactive molecules [116; 117; 118]. Chemical solvents known as supercritical fluids may be pressed exceeding their critical point, are often regarded as ecologically safe, and are frequently utilized in the extraction procedure because of their great performance and distinctive properties [119]. Many substances, including ammonia, ethane, ethane, fluoroform, nitrous oxide, propane, water, xenon and carbon dioxide can be used as supercritical fluids (SCF) [120]. Unquestionably, carbon dioxide is the one that is used the most frequently, because it is inexpensive, eco-friendly, and GRAS (generally acknowledged as safe) [121]. Furthermore, CO\({}_{2}\) is gaseous at normal temperature and pressure, making extract recovery relatively straightforward and enabling the production of extracts without the need of solvents [122]. The ability of SFE  
Figure 7: (**a**) Scheme of pressurized liquid extraction. (**b**) Specific variables that should be optimized for SFE extraction. employing CO\({}_{2}\) to be operated at low temperatures using a non-oxidant medium, which permits the extraction of thermally labile or readily oxidized chemicals, is also crucial for the extraction of food and natural products [123]. The limiting of the target compound and the inability to extract polar molecules is a SC-drawback, so in order to improve and aid in the polarity of SC-CO\({}_{2}\), ethanol must be added to the extraction system [124]. The limiting of the target compound and inability to extract polar molecules is SC-drawback. Ethanol can enhance SC-CO\({}_{2}\) mass-transfer and diffusivity [125]. Temperature, pressure, supercritical CO\({}_{2}\) flow, the presence of a modifier, and extraction time are the main variables that influence the SC-CO\({}_{2}\) extraction technique's effectiveness expressed as selectivity, yield, and/or extraction rate [126; 127] (Figure 7b). So, the impact of the important SC-CO\({}_{2}\) extraction parameters must be studied in order to enhance extraction yield [128]. According to [PERSON] et al. [129], with the introduction of supercritical carbon dioxide extraction, a wide variety of plant sources now serve as a significant source of bioactive chemicals with intriguing uses in complex sectors including food, pharmaceutical, and cosmetics. For example, [PERSON] et al. [130] applied supercritical CO\({}_{2}\) for the selective extraction of bioactive phytochemicals from black beans (_Phaseolus vulgaris_ L), [PERSON] et al. [129] for extraction of bioactive compounds from _Peganum harmala_ plant seeds, while [PERSON] et al. [131] used pure supercritical CO\({}_{2}\) and supercritical CO\({}_{2}\) with modifiers for bioactive compounds extraction from _Capsicum peppers_. [PERSON] et al. [132] and [PERSON] et al. [133] showed that the SFE-CO\({}_{2}\) extraction ensured a considerable increase in flavonoid production, antioxidant activity, and antiproliferative activity of the extracts compared with conventional Soxllet extraction and ultrasound-assisted extraction when _Xinjiang jujube_ leaves and _Puerariae lobatae_ root, _Pinus massonia_ needle, _Citrus reticulata_ peel and their mixture were used. Similar results were in the study by [PERSON] et al. [134] where flavonoids-rich extract (TF = 208.6-564.5 \(\upmu\)g/g) of dandelion seeds was prepared by SFE-CO\({}_{2}\) extraction at temperatures of 40 and 60 \({}^{\circ}\)C and pressures of 100 to 450 bar and in the study by [PERSON] et al. [135], in which a rutin-rich extract from blackberry seeds was prepared at 70 \({}^{\circ}\)C and 25 MPa using ethanol as co-solvent. In the extract prepped by [PERSON] et al.