**3.3 Supercritical carbon dioxide (CO2)**

CO2 as a liquid or supercritical solvent possesses multiple features of an admirable green solvent. They are incombustible, nonpoisonous, nonenvironmentally harmful, plentiful, inexpensive, easy to produce, simple to eliminate from a product, do not add to smog, and do not contribute to global warming [14]. Purified CO2 is produced, pressurized, and cooled to a liquid state at 20 psi and −20°C before being stored or transported in insulated bulk containers for use in a variety of liquid and supercritical CO2 processes. The viscosity of CO2 is extremely low, and supercritical CO2 has negligible surface tension [15]. The strong diffusivity, along with the low viscosity, causes significant improvements in the condensed phases. Supercritical fluid extraction of a crude drug is achieved by passing supercritical CO2 over a column packed drug material. Until the substrate is depleted, supercritical CO2 travels over the column of packed material and dissolves soluble components. The loaded solvent is then transported through a separator, where the soluble components precipitate as pressure and temperature are reduced. The CO2 is recirculated once it has been condensed. It is employed in the removal of caffeine from coffee and tea, the removing fatty material from cacao, the production of hops extracts, sesame seed oil, and pesticide extraction from rice. Under high pressure, SC CO2 is used to extract triglycerides and volatile compounds. Volatile, triglyceride and phenolic chemicals etc. are extricated at high

pressure (300–400 bars) with EtOH. Add water or alcohols like ethanol or iso-propylalcohol to the SC-CO2 extraction has already been used to modify the polarity [16].

#### **3.4 Deep eutectic solvents (DES)**

DES is formed when the melting point of a mixture of substances is much lower than the melting points of the two constituents. A hydrogen bond donor (HBD) and a hydrogen bond acceptor (HBA) are required to build a DES system, and when mixed in the right proportions, they generate a novel "mesh" of hydrogen-bond-interconnected molecules with remarkable physicochemical features [17]. Their extraordinary physicochemical features (like ionic liquids) combined with remarkable green properties, low cost, and ease of handling are piquing researchers' attention in a variety of sectors. The eutectic composition of DESs is formed by heating and stirring two or more solid starting components to generate a transparent, viscous homogenous liquid. Other techniques involve grinding (combining and powdering solid components till clear liquid forms), evaporation (dissolving all starting elements in water and then removing the water via evaporation at reduced pressure), and freeze-drying (dissolving all starting components in water and then draining the water via evaporation at reduced pressure).

Among them, heating and stirring below the melting points of the individual constituents is possibly the most acceptable method [18]. Because DESs are nonflammable and nonvolatile, they are easier to store. They are also biodegradable, unlike standard organic solvents. Furthermore, DES manufacture is cost-effective, simple to run, and requires no modification, making their use on a broad scale possible. DESs can be made by mixing molecules derived from natural sources (e.g., glycerol and glucose), which makes them environmentally friendly. Within the HBD section, polymerized deep eutectic solvents (PDEs) are a novel category of DESs that can be polymerized [17].

The high viscosity of DES is a key disadvantage that can limit their usage as extraction solvents since it prevents the solvent from penetrating the extraction matrix. Although increasing the temperature of the extraction process helps reduce viscosity, this is not always the best solution because it consumes energy, and some heatsensitive phytochemicals may not withstand the higher temperature. The addition of a co-solvent to the extraction medium is a straightforward technique to remedy this problem. Most of the time, this co-solvent is water, which keeps the process green; nevertheless, organic solvents like methanol have also been utilized. Alkaloids, phenolic acids, flavonoids, and saponins are all extracted using DES [19].

The DES is called natural deep eutectic solvents (NADES) when amino acids, organic acids, sugars etc. are used to make DES [20]. Due to the natural nature of its ingredients, NADESs are deemed environmentally beneficial and "readily biodegradable," and the resulting extracts can use in food, pharmaceutical, and cosmetics preparations. Because of their great stability and solubilization properties, NADES is ideal candidates to replace traditional solvents. NADESs combinations have efficiently extracted bioactive compounds including flavonoids, phenolic acids, alkaloids, natural pigments, sugars, peptides, and volatile components from natural matrices [21].

#### **3.5 Ionic liquids (IL)**

ILs were a type of organic salt that consisted of an organic cation (e.g., imidazolium, pyrrolidinium, pyrrolidinium tetra alkyl ammonium, pyrrolidinium tetra alkyl phosphonium) and an inorganic or organic anion (e.g., tetrafluoroborate, hexafluorophosphate, and bromide) that form of liquid below 100°C [22]. Because of their distinctive and construction dependent features, like low nucleophilicity, mixability with water or organic solvents, and good extractability, ILs have been frequently used [23]. A variety of organic and inorganic substances are perhaps enriched and separated using IL-based methods. As a result, they have been frequently used in food safety, drug testing, environmental monitoring, biological analysis, and other areas. The ability of ILs could be tailor-made for the extraction of alkaloids, flavonoids, terpenoids, phenylpropanoids, quinones, and other phytoconstituents from plants. A vast number of research organizations have also created IL-based silica and polymers that can improve the extraction/separation of target chemicals.
