Solvents are used in large amounts in different industries such as food and pharmaceutical to separate different valuable bioactive compounds. Over the last decade, the design of green, efficient and sustainable extraction methods has received a great attention from researchers. Great improvements can be achieved with the use of non-conventional techniques such as supercritical carbon dioxide extraction(SC-CO 2), Ultrasound Assisted Extraction (UAE) and Microwave-Assisted Extraction (MAE). In past decades, environmental friendly techniques are being interested to develop the ‘‘Green Chemistry” concept [1]. Therefore, an improved or better extraction technique is necessary. In the last 17 years (2000-2017), the extracts of more than 300 plant species have been studied using Supercritical Fluid Extraction (SFE) technology. The major share of SFE research covers plant material [2,3]. Many valuable pure components obtained from these plants are already in use for human nutrition and health purposes [4]. The most used solvent in supercritical state is carbon dioxide (CO 2) due to its great versatility, non-explosive, non-flammable, non-toxic and cost-efficient properties and easy to remove from the solutes [5].CO 2 is classified as a low-critical temperature solvent. A good feature of low-critical temperature solvents, as compared with conventional liquid solvents, is that they operate at moderate temperature and provide thermo degradation of thermally labile compounds. These solvents are highly preferred in pharmaceutical and natural-product industries. A major advantage of low-critical temperature solvents is their easy separation from the extract [6]. Generally, supercritical carbon dioxide (SC-CO 2) which possesses properties of both liquids and gases has several major advantages compared with liquid solvents. Figure 1 shows the pressure-temperature phase diagram of CO 2. A pressure-temperature phase diagram of CO 2 indicates the temperature and pressure conditions necessary for the various states of substance to exist. The critical temperature for carbon dioxide is 31.1°C, and the critical pressure is 73 atm. above the critical temperature and pressure, the fluid is called supercritical fluid. The isothermal compressibility of a fluid near its critical point is infinity, which translates into rapid change in its density as a function of temperature and pressure. The density of a supercritical fluid which affected the dissolving power is strongly tunable by varying the temperature or/and pressure. Therefore, selective fractions can be extracted from natural sources by carefully choosing the temperature and pressure operation [7,8].
list of fluids which have been proposed as supercritical fluid solvent was shown in Table 1. It has been shown that N 2 O cause violent explosions when used for samples having high organic content and should, therefore, be used only when absolutely necessary.The possible practical applications of super critical H 2 O has been limited due to its high critical pressure and temperature (T >374 ºC and P > 221 bar) together with the corrosive nature of H 2 O at these conditions [2].Other solvents (e.g. ethane, propane) have also been used in studies but their use is limited compared with CO 2 and for this reason the emphasis of this review is on SC-CO 2.
deMelo et al. (2014) presented a review regarding the plant species that have been studied under the scope of SFE. It has been stated that supercritical fluids have been mainly applied to the extraction valuable compounds from seeds and leaves which are followed by fruits, roots, flowers, rhizomes and bark [4]. Different valuable bioactive compounds including triglycerides, fatty acids, fatty alcohols, terpenoids, phytosterols, tocopherols, tocotrienols, and phenolics can be obtained applying SC-CO 2 from plant matrices.
A triglyceride is an ester derived from glycerol and three fatty acids. Triglycerides are the main constituents of body fat in humans and animals, as well as vegetable fat. Furthermore it is known that their abundance in extracts lead to high quality biodiesel. Based on our knowledge there is lack of information about SFE application covering this purpose. Free fatty acids are also a specific family of compounds that occur independently in SFE extracts. In some cases the control of free fatty acid concentration may be helpful to quality control of the oils. Moreover, these compounds are key stones for soaps, oleochemical esters, oils and lubricants [9]. These compounds have been studied widely as target compounds for extraction, such as in SFE of borage (Borage officinalis L.) [10], primrose (Oenotherabiennis L.) [10], chinese star anise (Illiciumverum) [11], palm (Elaesguineensis)[12], pine (Pinussylvestris L.) [13], pupunha (Guilielmaspeciosa) [14], winter melon (Benincasahispida)seed [15, 16], spearmint (Menthaspicata L.) [17-19] and Strobilanthescrispus (pecahkaca) [20].
Terpenoids are a large and diverse class of naturally occurring chemicals found in plant sources. These compounds are secondary metabolites whose role in plants is related to protection, pollination and growth mechanisms [21]. Plant terpenoids are used extensively for their aromatic qualities and play a role in traditional herbal remedies. The extraction of these compounds has been one of the major objectives driving SFE research. These compounds are classified to five subgroups according to the number of isoprene units. Monoterpenoids, with two isoprene units, such as geraniol [22,23]; sesquiterpenoids, three isoprene units, such as parthenolide [24]; diterpenoids, with four isoprene units, such as cafestol [25]; triterpernoids, with six isoprene units, such as ursolic acid [26-28]; tetraterpenoids, with eight isoprene units, such as lycopene [29,30].
Phenolic compounds could act as hydrogen donators, singlet oxygen quenchers and reducing agents because of their redox properties [20]. Literatures pointed out phenolic compounds are responsible to reduce the risk of coronary heart diseases, stroke, cancer, degenerative and atherosclerosis diseases attributed to oxidative stress [18]. Phenolic compounds which present in edible and non-edible plants show various biological effects such as antioxidant activity. Plant materials crude extracts which contain high amount of phenolic compounds lead to reduce the rate of lipid oxidation and improve the quality of food products are strongly favoured in food industry. In addition, it was revealed that phenolic compounds like flavonoids can act as scavengers of Reactive Oxygen Species (ROS) through oxido-reductases inhibition [20]. Depending on the vegetable species, extracts obtained by SC-CO 2 can comprise substances from several phenolic groups like coumarins [31], cinnamic acids [32], quinones [33], flavonoids [17-20], lignans [32].
There are several parameters such as plant material preparation, selection of supercritical fluids, modifiers and extraction conditions which affected strongly the efficiency of SFE process. Hence, they should be considered carefully to develop a successful process.
Preparation of plant materials is a critical step for SFE process. Fresh plant matrices contain high moisture content which cause mechanical problems due to ice formation. Furthermore, the efficiency of SFE process will reduce due to the high watersolubility of compounds dissolved in aqueous phase while the water solubility (0.3%) in SC-CO 2 is very low [34]. Therefore, it is necessary to control the moisture content of plant matrices by drying or mixing them with chemicals like sodium sulphate and silica gel. It has been stated that when the moisture content of Benincasahispida seeds was increased from 5 to 20% the crude extraction yield was decreased up to 38% [35]. Saldana et al., (2004) found that 10% moisture content was adequate to reach high recovery of β-carotene from apricot pomace by SC CO 2 extraction. The plant matrices particle size could be considered as another critical parameter for SC-CO 2 extraction of nutraceuticals as the extraction process controlled by internal diffusion feed. The extraction time is extended by using larger particle size of samples. In contrast, fine powder can increase the rate of extraction; however, it is difficult to keep flow rate properly. By referring to different published literatures, it was believed that a smaller sample particle size results in greater extraction of lycopene by SC-CO 2[36-39].
The solvent properties of supercritical fluids may be tuned by changing pressure and temperature values, directly influencing density. The solubility of targeted compounds in SC-CO 2 is mainly determined by the SC-CO 2 density. In general, SC CO 2 density increases with pressure at constant temperature and decreases with temperature at constant pressure, where the density decrease becomes smaller at higher pressures. The majority of the studies indicated that an increase in the extraction pressure of the supercritical carbon dioxide leads to an increase in the amount of valuable bioactive compounds extracted [6]. Bimakr et al. (2011) utilized pressure of 100 to 300 bar in the extraction of bioactive compounds spearmint (Menthaspicata L.) leaves. They found that the extraction yield increased with pressure from 100 to 200 bar, which was due to increase of SC-CO 2 density at higher pressures. However, an increase in the pressure level above 200 bar led to an unexpected reduction in the extraction yield. Liza et al. (2010) also found that at pressure above 200 bar there was non-existent of any flavonoid compounds. Moreover, same behavior was reported by Liu et al. (2009) in SCE of pomegranate (Punicagranatum L.) seeds. They found that an elevation of pressure (up to around 320 bar) caused significant increase of crude yield extract. They mentioned that this result most likely was due to the improvement of solute solubility resulted from the increased solvent density [39].
As mentioned above the density of CO 2 affected by the temperature. The density of CO 2 at constant pressure is reduced with increasing temperature and leading to reduce the solvent power of supercritical CO 2. Temperature also affects the volatility of the solute. Hence, the effect of a temperature elevation is difficult to predict because of its dependence on the nature of the sample. For a non-volatile solute, a higher temperature would result in lower extraction recovery owing to a decrease in solubility. A temperature increase may also cause breakdown of cell structure and increase the diffusion rate of the targeted compounds in the particles, therefore accelerating the extraction process [6]. Bimakr et al. (2011) studied the effect of temperature on SC-CO 2 extraction of bioactive compounds from spearmint leaves. They obtained that the extraction yield increased with temperature and the highest extraction yield (60.57 mg/g) was obtained at 60°C. In this manner, the solute vapour pressure played a key role leading to increase in the extraction yield [18].
Extraction time is another important parameter that needs to be optimized for maximizing bioactive valuable compounds recovery from plant matrices. The extraction time could be helpful parameter to obtain a complete SC-CO 2 extraction. To enhance the efficiency of SC-CO 2 process it is necessary to prolong the contact time of the SC-CO2with the sample material. Due to the physical structure of the seed, the penetration of the solvent and the diffusion of targeted compounds in the particles are very slow. Therefore, extraction time is usually limited to the fast extraction period since the amount of extraction yield recovered in the slow extraction period is negligible. Bimakr et al. (2013) examined the effect of extraction time at 60, 90 and 120 min on valuable compounds recovery from Benincasahispidaseeds. They found that the highest crude extraction yield (176.30 mgextract/gdried sample) was obtained at 97 min. According to them, it was possible that 60 min of extraction time was insufficient for a complete extraction, while thermal degradation occurring at 120 min of extraction led to lowered yields of valuable bioactive compounds [16]. Reducing the extraction time could also reduce costs as well as improve energy efficiency [37]. In a study conducted by Ozkal et al. (2005) fast extraction period decreased from 183 to 64 and 32 min with a pressure increase from 30 to 45 and 60 MPa at 40°C. On the other hand, it decreased from 64 to 33 min with a temperature increase from 40°C to 50°C at 45 MPa. Furthermore, it was reported that, a 10-20 min static extraction prior to dynamic extraction improved the extract recoveries in SFE extraction of aflatoxins [40].
Bimakr et al. (2011) investigated the effect of dynamic time on the SC-CO 2 extraction of valuable compounds from Menthaspicata L. leaves. They concluded that the solvent power of SC-CO 2 is reduced at 100 bar pressure due to the lower CO 2 density so maximum yield was obtained during 90 min dynamic extraction time. Applying higher pressures (200 and 300 bar) the extraction rate is higher and as a consequence the extraction yield kept increasing up to 60 min dynamic extraction time[18]. In another study, Bimakr et al. (2016) shortened the extraction time using supercritical carbon dioxide extraction combined with pressure swing technique (SCE-PST). They found that application of pressurization-depressurization before continuous extraction time had a significant effect on improvement of extraction efficiency [15].
The speed of the supercritical fluid flowing through the cell has a strong influence on the extraction efficiencies. The slower the fluid velocity, the deeper it penetrates the matrix. Papamichail et al. (2000) studied the SFE of oil from milled celery seeds using CO 2 as a solvent. They investigated the effect of flow rate of CO 2 on the extraction rate of celery seeds. They showed that the increase of the solvent flow rate leads to the increase of the amount of oil extracted versus extraction time [41]. Topal et al. (2006) tested SC-CO2 flow rates ranging from 1.5 to 4.5 mL/min and found the highest lycopene yield at a flow rate of 2.5 mL/min. Using the flow rate between 2.5 to 4.5 mL/min a decrease in the amount lycopene extracted was observed [38].
An important shortcoming of the use of SC-CO 2 is its low polarity. Considering the chemical nature of most natural bioactive compounds, generally polar compounds,CO 2 alone may not be able to extract them. To cope with this issue, co-solvents (also called modifiers) are empl
