Supercritical carbon dioxide extraction
Rawiya H. Alasbahi | Department of Pharmacognosy, Faculty of Pharmacy, University of Aden, Yemen
The present paper deals with a literature review of the different aspects of supercritical carbon dioxide extraction (SFE). It summarized the general properties of SFE as an advanced and excellent alternative to conventional extractions methods, as well as the advantage and disadvantage of using supercritical CO2 as an environmentally safe and effective solvent. The study also covered the different applications of SFE in food and pharmaceutical processing, and to extract valuable compounds with bioactivities such as antioxidant, antitumor and antibacterial from plant species as well as to produce valuable compounds form industry by-products and new functional ingredients that can be used by the food industry. The study also highlighted the use of SFE in food safety and environmental protection such as the detection/ quantification as well as the removal of food and environmental pollutants.
Key words: Supercritical CO2 extraction, Applications
Traditionally, several techniques have been used for sample preparation involving extraction with organic solvents, column fractionation, etc. These are usually time-consuming and labor-intensive, introducing potential quantitative errors and using large volumes of organic solvents, with the associated risks for the human health and the environment (Mendiola et al., 2007). In response, the Montreal Protocol was introduced in 1987 with an initial objective to restrict or eliminate the manufacture and use of particularly damaging ozone depleting solvents such as chlorofluorocarbons (CFCs). The Montreal Protocol is dynamic and evolving with the manufacture and supply of solvents other than CFCs gradually being restricted. Years of negotiation fostered by the United Nations Environment Program has now resulted in more than 170 signatory nations to the Montreal Protocol with its London (1990), Copenhagen (1992) and Beijing (1999) amendments. Consequently, worldwide there is pressure for industry to adopt new sustainable processes that do not require the use of environmentally damaging organic solvents (Ramsey et al., 2009). Currently various approaches have been developed to replace the conventional organic solvents with eco-friendly solvents like supercritical CO2 (SCCO2). It has been reported that carbon dioxide is used in more than 90% of all analytical supercritical fluid extractions (Pourmortazavi & Hajimirsadeghi 2007). Since the end of the 1970s, supercritical fluids have been used to isolate natural products, but for a long time, applications relayed only on few products. Now the development of processes and equipment is beginning to pay off and industries (chemical engineering, chemistry, food industry, agronomy industry, biotechnology and environmental control) are getting more and more interested in supercritical techniques (Brunner 2005). The aim of this study was to provide an overview on the supercritical CO2 extraction as a powerful, cleaner and cheaper technique that is useful in food, chemical, pharmaceutical and environmental sciences.
In the supercritical environment (at a temperature and pressure above the critical values), only one phase exists. The fluid, as it is termed, is neither gas nor liquid and is best described as intermediate to the two extremes. This phase retains gas-like properties of diffusion, viscosity, and surface tension, and liquid-like density and solvation power. Consequently, the rates of extraction and phase separation can be significantly faster than for conventional extraction processes due to the low viscosities, low surface tensions, high diffusivities, and high solvation associated with supercritical fluids. Furthermore, the extraction can be selective to some extent by manipulating the density of the fluid through control of the system pressure and temperature.
The extracted material is easily recovered by simply depressurizing, allowing the supercritical fluid to return to gas phase and evaporate leaving no or little solvent residues (Askin & Ötles 2005; Brunner 2005; Bravi et al., 2007; José et al., 2007; Montañés et al. 2008; Azmir et al., 2013).
Supercritical fluid extraction (SFE) using carbon dioxide (CO2) represents an innovative and efficient technique to produce a high quality “clean” extract with no solvent residues (Beckman 1996; Raventos et al., 2002). From the viewpoint of pharmaceutical, nutraceutical and food applications, supercritical fluid (CO2) extraction (SFE) has the following advantages and disadvantages (Rozzi & Singh 2002; Askin & Ötles 2005; José et al., 2007; Sahena et al., 2009; Herrero et al., 2010; Ciftci O.N. 2012; Joana Gil-Chávez et al., 2013; Girotra et al., 2013; Azmir 2013; Shams et al., 2015; Nautiyal 2016).
Carbon dioxide is a good solvent, because it is odorless, colorless, highly pure, non-toxic, non-flammable, inexpensive, recyclable gas, easy to remove from the product, and its critical temperature and pressure are relatively low (critical conditions = 30.9 ◦C and 73.8 bar) make it important for food and natural products sample preparation.
Carbon dioxide is environmentally friendly and generally recognized as safe by The Food and Drug Administration (FDA) and The European Food Safety Authority (EFSA).
The ability of SFE to be operated at low temperatures using a non-oxidant medium allows the extraction of thermally labile or easily oxidized compounds.
Enhanced extraction efficiency.
Compared with the 20–100 g of sample typically required in classical extraction methods, as little as 0.5–1.5 g of sample is needed in SFE methods. It has been reported that from only 1.5 g of fresh plant samples, more than 100 volatile and semi-volatile compounds could be extracted and detected by gas chromatography –mass spectroscopy (GC-MS), of which more than 80 compounds were an in sufficient quantity for accurate quantifications.
SFE uses no or significantly less environmentally hostile organic solvents, while classical extraction methods require tens to hundreds of milliliters.
Substantially reduction of extraction time.
The selectivity of supercritical fluid is higher than liquid solvent as its solvation power can be tuned either by changing temperature and/or pressure. This tunable solvation power of SCF is particularly useful for the extraction of complex samples such as plant materials. One good example is the selective extraction of a vindoline component from among more than 100 alkaloid compounds from the leaves of Catharanthus roseus. Selectivity can also be changed by the addition of a co-solvent such as ethanol, methanol, hexane, acetone, chloroform and water to increase or decrease the polarity. Ethanol is the most preferred co-solvent because it is non-toxic and meets ‘green’ technology criteria.
Preservation of bioactive and organoleptic properties of the extracts.
SFE can be applied to systems of different scales, for instance, from analytical scale (less than a gram to a few grams of sample), to preparative scale (several hundred grams of sample), to pilot plant scale (kilograms of sample) and up to large industrial scale (tons of raw materials, such as SFE of coffee beans).
The recycling and reuse of supercritical fluid is possible and thus minimizing waste generation.
On-line integration with sample preparations and detection methods. For examples, SFE has been directly coupled to a capillary electrophoresis (CE) instrument with fluorimetric detection to effectively carry out the clean-up of the sample and the direct CE analysis of riboflavin from chicken liver and powdered milk (Zougagh & Rios 2008). Another direct coupling was with Fourier transform infrared spectroscopy (FTIR) to determine tagitinin C (a sesquiterpene lactone, with anti-plasmodial activity) that was extracted fromTithonia diversifoliausing CO2 (Ziemons et al.,2007)
The low polarity of carbon dioxide (suited for the extraction of lipophilic compounds), problem that can be overcome by employing polar modifiers (co-solvents) such as methanol and ethanol to change the polarity of the supercritical fluid and to increase its solvating power towards the analyte of interest. Another method to decrease analyte polarity and make them more soluble in non-polar supercritical fluids is the in-situ derivatization that has been applied to improve the selectivity of the extraction towards a specific group of compounds.
High capital investment.
Large number of variables to optimize.
Strong dependence on matrix analyte interactions.
Difficulties in scale up and technology transfer.
Difficulty in extracting more polar compounds.
Principle of extraction
SFE is a two-step process which uses a dense gas e.g., carbon dioxide, as a solvent for extraction, above its critical temperature (31C°) and critical pressure (74 bar). The feed, generally ground solid, is charged into the extraction vessel. Carbon dioxide is fed to the extraction vessel through a high-pressure pump (100 to 500 bars). The extract rich carbon dioxide is then sent to a separation vessel, which maintained at reduced pressure and temperature conditions, and the extract precipitates out in the separation vessel. The extract free carbon dioxide stream, leaving the separation vessel is then recycled back to the extraction vessel till the end of the batch. Extraction process may be static (sample and fluid sealed in an extraction vessel), dynamic (fluid flows through the vessel), off-line (analytes are collected for later analysis) or on-line (analytes are directly transferred to a coupled instrument such as a gas chromatography modes. Static extraction is preferred in situations dealing with low concentration of active constituents strongly bound to matrix. The efficiency of SFE depends upon the modifier (type and amount) and extraction parameters (time, temperature, pressure) (Basniwal et al., 2005). To be truly useful in the analytical laboratory, the SFE technology must be thoroughly understood. A hasty approach to method development can lead to problems and even disillusionment with the technology. Lack of understanding regarding system parameters (e.g. type of fluid, density, pressure, temperature, flow rate, extraction time, analyte collection) can result in misinformation and erroneous conclusions. In order to do further SFE analysis, the system should be well understood. (Askin and Ötles 2005). Therefore, one of the main aspects that should be considered in SFE is the extraction optimization. It is very important to organize the experiments based on the fundamentals (phase equilibrium strategies and experimental design statistical optimization) that contribute to the understanding of the extraction problem (Herrero et al., 2010).
Comparison of supercritical fluid extraction to conventional methods
The performance of SFE compared to other advanced and/or conventional extraction techniques has been frequently evaluated in a number of studies, for examples, investigation of different extraction methods including steam distillation, solvent extraction, supercritical fluid extraction and liquid CO2 extraction to obtain the volatile oil from Western Australian sandalwood (Santalum spicatum(R. Br.) A. DC.) has revealed that the highest yields of extractable material and total volatile compounds was obtained by SFE (Piggott et al., 1997). SFE was also found to provide faster extractions and higher yields than hydrodistillation for the extraction of the essential oil ofValeriana officinalis. However, hydrodistillation extracted more components of essential oil than SFE, although the loss of these compounds in the depressurization step after SFE was a possibility to consider (Herrero et al., 2010). The SFE method has been demonstrated to be superior to hydrodistillation, regarding the higher yield of essential oils extracted from 2 Eucalyptus species (Eucalyptus cinereaand Eucalyptus camaldulensis), with a promising radical scavenging activity and shorter extraction times (Herzi et 4 al., 2013). Doneliana et al (Doneliana et al., 2009) compared extraction of patchouli (Pogostemon cablin) essential oil with SCCO2 and by steam distillation and they found that the extraction of patchouli essential oil with SCCO2 gave the best yield (5.07%), which was higher than that of steam distillation (1.50%). It was reported that the quantity (yield and phenol content) and quality (antioxidant activity) of extracts obtained from the seeds of Benincasa hispidaunder optimum condition of SCCO2extraction was better than those obtained at optimized ultrasound-assisted extraction (Bimakr et al.,2013). SFE was found to extract higher phenolic concentrations from grape pomace than the solid–liquid extraction, although the composition of the extracts was not exactly the same, while solid–liquid extraction contained more proanthocyanidins, SFE was richer on simple phenolics (Pinelo et al.,2007). Mango (Mangifera indicaL.) skin waste was extracted by employing supercritical CO2 followed by pressurized ethanol (PE) from the residue of the first stage, conventional ethanol extraction (CE) was also done. The extracts obtained were evaluated by spectrophotometric method in terms of Total Carotenoids Content (TCC), Total Phenolic Content (TPC), Total Flavonoids Content (TFC); and Antioxidant Activity (%AA). The results demonstrated that TCC value was high by SCCO2 extraction and follow the trend SCCO2 ˃ CE˃ PE meanwhile for TPC and %AA, the trend was CE ˃ PE ˃ SCCO2. The higher total flavonoids content was obtained by conventional ethanol extraction and therefore, it was considered that SCCO2 was efficient to extract the low polarity fractions of flavonoids (Nautiyal 2016). It has been demonstrated that a combination of ultrasound pretreatment of sage (Salvia officinalisL.) with distilled water followed by re-extraction of obtained extract with supercritical CO2 gives two valuable products: The ultrasound extract which is rich in sugars and possess the immunomodulatory activity and supercritical extract which is rich in diterpenes and sesquiterpenes (Glisic etal.,2011). Moreover, SFE has showed to be more effective for the extraction of antimicrobial compounds (Liu et al., 2009; Michelin et al., 2009).
Nowadays, SFE is much used in many food industrial applications including decaffeination of coffee (Joana Gil-Chávez et al., 2013; Shams et al., 2015) and tea (Kim et al.,2008), extraction and fractionation of carbohydrates (Herrero et al., 2010), crude vegetable oils refining such as wheat germ oil (Eisenmenger & Dunford 2008), green coffee oil (De Azevedo et al., 2008), rice bran oil (Chen et al., 2008) and crude palm oil (Davarnejad et al., 2008), extraction and fractionation of essential oils for use in the food, cosmetics, pharmaceutical and other related industries, producing high-quality essential oils with commercially more satisfactory compositions (lower monoterpenes) than obtained with conventional hydrodistillation (Mohamed & Mansoori 2002; Herrero 2010; Joana Gil-Chávez et al.,2013; Shams et al., 2015; Girotra et al., 2013), extraction of vitamin A and E from powdered milk, fluid milk, meat, extraction of lipids from variety of meats, nuts and seeds and fractionation of lipids of dairy products (Askin & Ötles 2005), extraction of fatty acids (Herrero et al., 2010), natural food colorants (Shams et al., 2015), flavor (Joana Gil-Chávez et al., 2013), and omega-3 enriched fractions from fish oils (Herrero et al., 2010). SFE has also been used to determine the fat content of numerous products ranging from beef to oil seeds and vegetables (Rozzi &Singh 2002) and to produce fat free or fat-reduced food such as potato chips. SFE has also been employed in the de-alcoholization process of alcoholic beverages (Abbas et al., 2008; Herrero et al., 2010) and in the determination of amino acids profiles in different genetically modified varieties of maize and soybean (Herrero et al., 2010).
SFE using carbon dioxide has been widely used to value food industry by-products. These products are generated during food manufacturing and normally do not have any commercial value. By-products extraction allows the removal of valuable/interesting compounds such as compounds with antioxidant capacities (e.g. polyphenols, carotenoids) that otherwise cannot be utilized. For instances, the removal of polyphenols from rice wine lees and the carotenoids (mainly lycopene), tocopherols and phytosterols from tomato pomace. (Venturi et al., 2017; Herrero et al., 2010). Carotenoids and tocopherols recovery from sea buckthorn pomace (a by-product of sea buckthorn juice manufacture process) and from fresh palm-pressed mesocarp fiber (by-product from palm oil production) has also been studied. Omega-3 rich extracts were obtained from hake by-products. Other examples are the extraction of long chain n-alcohols from sugar cane crude wax, coming from sugar cane production, polyphenols from pomegranate seeds (from juice production), phytosterols from loquat seeds, and caffeine from tea stalk and other tea plant wastes. Many works deal with oil recovery from different residues, namely, wood, corn or even silkworm pupae (Herrero et al., 2010).
Natural products applications
In the last 17 years, the extracts of more than 300 plant species have been studied using SFE technology. The major share of SFE research covers plant material. Many valuable pure components obtained from these plants are already in use for human nutrition and health purposes. Different valuable bioactive compounds including among others triglycerides, fatty acids, fatty alcohols, glycosides, waxes, terpenoids, phytosterols, tocopherols, tocotrienols, xanthones, oleoresin, alkamides, phenolic acids, flavonoids, anthocyanin, coumarins, carotenoids, and phenolic compounds have been obtained from extracts and essential oils of plant matrices by applying SCCO2 (Askin & Ötles 2005; Cavero et al., 2006; Juan et al., 2006; Herrero et al., 2010; Bimakr & Ganjloo 2016; Nautiyal 2016 ; Sovilj et al., 2011; Karale Chandrakant et al., 2011; Xu et al., 2011).
Search for functional compounds
Nowadays, the growing interest in the so-called functional foods has raised the demand of new functional ingredients that can be used by the food industry (Herrero et al., 2006). Supercritical fluid extraction using CO2 is an environmentally clean extraction method that can provide extracts characterized by preserved chemical composition and biological activity. As reported in the literature (Da Silva et al., 2016), the bioactivities from natural compounds extracted by SFE from 2010 to 2015 were mainly the antioxidant. (41%), antitumor (18%), and antibacterial (10%) ones.
The application of SFE to produce extracts with novel pharmaceutical activities are illustrated in the following examples: most pharmacological studies on mistletoe (Viscum album) have focused on the therapeutic properties of its polar extracts; but Ćebović et al. (Ćebović et al., 2008) examined the biological activities of the non-polar constituents ofViscum album, which were obtained by supercritical CO2 extraction and identified by coupled gas chromatography/mass spectrometry (GC/MS). Several new terpene compounds were identified by this method, which were found to exhibit cytotoxic properties in Ehrlich carcinoma cells in vivo. Squalene with antioxidant activity has also been extracted with supercritical carbon dioxide from different matrices such as olive oil, oil-refining by-products and from different plants (Mendiola et al., 2007). Algae and microalgae have been searched for feasible new sources of natural antioxidants and functional compounds that could be employed in the food industry. The antioxidant activity of supercritical extract of Dunaliella salinamicroalga, which is known to contain carotenoids was studied by Rupérez et al. (Rupérez et al., 2009). They performed metabolic fingerprinting and target metabolite analysis of D.salinamicroalga extract on rats. Other microalgae were investigated in order to determine their composition on particular carotenoids, for instance, 87% of total lutein in Chlorellapyrenoidosa. This carotenoid is interesting not only for its antioxidant activity but also for being useful for prevention of age-related macular degeneration. Authors found that the selectivity of SFE using supercritical CO2 allowed the attainment of high purity products, therefore suggesting that the process could be used for lutein commercial production. Another example is the obtaining of functional food oil (soybean oil) that was enriched with antioxidants fromChlorella vulgaris. Carotenoids have not been the only target compounds. In fact, the extraction of γ-linolenic acid from Spirulina platensisby SFE has been also studied, as well as the tocopherols content in the same microalgae (Herrero et al., 2006). Moreover, SFE extract of Tabernaemontana catharinensis(jasmine) has been tested on Lehismaniosis. The alkaloidal fraction of the extract was analyzed with TLC, GC–MS, and other spectrometric methods such as IR, UV and H1 NMR, and it was revealed that besides coronaridine and voacangine (two previously characterized indolic alkaloids), the alkaloidal fraction contains voacangine hydroxylindolenine, voacristine, voacristine hydroxylindolenine, and 3-hydroxylcoronaridine. This study concluded that SFE is an efficient method for the extraction of bioactive indole alkaloids from plant extracts, while retaining the alkaloids properties associated with inhibiting Leshismania amazonensisamastigote replication in macrophages without incurring host cell toxicity (Soares et al., 2007). SFE has been widely used as sample preparation method to analyze essential oils from foodstuffs like onions, or from different herbaceous materials like oregano, rosemary, laurel (bay leaves), cinnamon, cumin, horsetail or St John’s wort. Essential oils are not only valuable as aroma but also some of them are highly appreciated as functional ingredients with different activity such as antioxidant (oregano), antimicrobial (rosemary), and antidepressant (St. John’s wort) (Mendiola et al., 2007). Other application of SFE was the search of new compounds with antiviral activity from wild and cultivated sage (Salvia officinalis) extract, which indicated that antiviral activity of this extract involved inhibition of the early steps of the vesicular stomatitis virus infective cycle without a direct virucidal effect (Smidling et al., 2008). Searching for anti-atherogenic and cardioprotective activities (Basu et al.,2007) and wound healing properties (Upadhyay et al., 2009) of Sea buckthorn (Hippophae rhamnoidesL.) extract has demonstrated that the cardioprotective effects may be attributed to the synergistic effects of its content of omega-3 and omega-6 fatty acids, tocopherols, phytosterols and β-carotene. The wound healing process was evidenced by a significant increase in wound contraction, hydroxyproline, hexosamine, DNA and total protein contents in comparison to control. Other examples of using SFE to extract valuable compounds from foods were the isolation of fat-soluble vitamins from parmigiano regiano cheese [Abbas &. Ötles 2008] as well as the enrichment of vitamin E from crude palm oil and soya oil deodorizer distillate (Chuang & Brunner 2006; Fang et al., 2007).
SFE in pharmaceutics
The main uses of supercritical fluids in pharmaceutical industry include processes of micronization, preparation of nanoparticles and crystal engineering, production of polymeric scaffolds, formation of complexes with cyclodextrins, coating, foaming and tissue engineering, polymer processing, enzymatic reactions in supercritical media, extrusion, production of liposomes and biotechnological compounds , enhancing the solubility and dissolution rate of drugs and excipients, purification of pharmaceutical excipients, sterilization, solvent removal, enantioselective separations, supercritical drying, and, of course, extraction and purification of active principles from raw materials and from synthetic reaction media (Mukhopadhyay (2000); Riegr & Horn 2001; Pessoa & Uller 2002; Abbas etal.,2008; Herrero et al., 2010; Girotra et al., 2013; Akshay et al., 2015; Shams et al.,2015).
SFE in food toxicology and ecotoxicology
At present, food safety includes many different issues such as detection of frauds, adulterations, contaminations, etc. Among these topics, the detection of food pollutants is important not only for consumers but also for administrations, control laboratories, and regulatory agencies. In order to protect consumers’ health, regulations establish strict limits to the presence of pollutants in foods that must be carefully observed and determined. Generally, the analysis of food pollutants is linked to long extraction and cleanup procedures commonly based on the use of, e.g., Soxhlet and/or saponification. These procedures are laborious and time consuming and,besides usually employ large volumes of toxic organic solvents. With the objective of reducing both, the sample preparation time and the massive use of organic solvents, techniques based on compressed fluids such as SFE have been developed. One of the main areas of application of SFE in the last few years has been in food pollutants analysis, mainly pesticide residues and environmental pollutants (Mendiola et al., 2007). SFE has been used to extract and measure toxic contaminants such as polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), polychlorinated biphenyls (DL-PCBs), dioxins, polyaromatic hydrocarbons (PAHs), pesticides, insecticides, heavy metals in soils, sediments, municipal wastewater, river sediments and floodplain, fish, seaweeds and aquaculture products (turbot, clam, mussel and cockle), and plants. (Herrero et al., 2010). In addition, SFE has been adopted by the EPA (The United States Environmental Protection Agency) as a reference method for extracting Petroleum Hydrocarbons (Method 3560, in 1996) PAHs (Method 3561, in 1996) and PCBs (Method.(3562, in 2007) from solid environmental matrices (Herrero et al., 2010). SFE has been applied for the analysis of multiple pesticides in potatoes, tomatoes, apples, lettuces, honey, cereals, fish muscle, vegetable canned soups, vegetables or infant and diet foods as well as for the quantification and control of the pollutants such as polyaromatic hydrocarbons and halogenated dioxins and biphenyls that may be found in food (Mendiola et al., 2007). SFE has been recently used for extracting POPs (persistent organic pollutants) from different plant materials, and several analytical applications dealing with POPs extraction from different animal tissues have also been reported (Herrero et al., 2010). In addition, SFE has been used to measure veterinary drugs residues such as orbifloxacin (third-generation fluoroquinolone antibacterial drug used in ruminant farming) in plasma and milk (Herrero et al., 2010), and lasalocid, which is widely used as a coccidiocidal drug in poultry to increase feed efficiency and for weight gain in ruminants as well as sulphonamides, which are commonly used in subtherapeutic doses in drinking water but also as bacteriostatic in chicken, beef and pig grown (Mendiola et al., 2007). Moreover, a SFE method has been developed by Gadgil et al (Gadgil et al.,2005) to estimate the irradiation dose in irradiated meat by measuring the content of irradiation byproducts such as alkylcyclobutanones that are formed when fatty acids are irradiated.
Several recently developed applications of supercritical fluids not only tend to eliminate organic solvents, but also to reduce the environmental impact of human activities. In this sense, applications like removal of heavy metals from soils, removal of commonly used solvents of varying polarities from aqueous waste streams, sludge and wastes, reduction of secondary wastes generation, regeneration of inactive catalysts or methods for treating soils contaminated with non-polar compounds (PAH, PCB, etc.) are being studied (Herrero et al., 2010; Leazer et al., 2009).
Removal of heavy metals from solid matrices and liquids remains a big challenge and, although various methods have been described for this purpose, SFE seems to be one of the most promising (Sunarso & Ismadji 2009). Supercritical CO2 extraction was used to remove harmful elements such as copper, lead and arsenic from Polygonum multiflorum, used a Chinese traditional medicine (Wen et al., 2008). Wang and Chiu (Wang &Chiu 2008) developed a green method using supercritical carbon dioxide containing an organophosphorus reagent to remove chromated copper arsenate, which has been used extensively as a wood preservative since1940. After shelf life, treated wood caused environmental hazard, therefore, metal removal is highly important. Moreover, the surface decontamination of radioactive metal wastes using acid-in-supercritical CO2 emulsions have been proposed by Koh et al. (Koh et al., 2008) as an effective candidate for surface decontamination of radioactive metals in the near future.
SFE using supercritical CO2 is an alternative green technology to conventional extractions techniques due to its use of environmentally safe fluid and the flexibility of the process that allows the continuous modulation of the solvent power and selectivity of the supercritical fluid, thus ensuring a safe and effective separation process for human health and the environment. Several applications of SFE have been developed and commercialized, some in food industry such as new foods, food ingredients/additives, in pharmaceutical products, or to get new useful compounds from industrial byproducts, and to extract valuable pure natural components to be used for human nutrition and health purposes as well as to allow detection, quantification and /or removal of toxic compounds or heavy metals from food and the environment.
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