Supercritical Fluid Extraction Technology Research Articles

Efficient isolation of polyunsaturated amides from Zanthoxylum bungeanum and assessment of their anti-inflammatory potential

A targeted extraction, enrichment and separation method for polyunsaturated amides from Zanthoxylum bungeanum was established. Three main polyunsaturated amide monomers with high purity were isolated at the same time: hydroxyl-α-sanshool (HAS), hydroxyl-β-sanshool (HBS), hydroxyl-ε-sanshool (HES). This efficient method combined high-pressure supercritical fluid extraction (HPSFE) and industrial chromatography purification technology. By studying the extraction kinetics of target polyunsaturated amide monomers, the operation parameters of HPSFE were optimized. Meanwhile, a HPLC method for simultaneous determination of three polyunsaturated amide monomers was established in order to optimize process. Under the optimal conditions of high-pressure extraction, the extraction equilibration time was 45 min, the content of total polyunsaturated amides reached 27.53 %, and the yield was 2.89 %. At last, three high-purity polyunsaturated amide monomers were obtained, namely HES (95.16 %), HAS (98.43 %), and HBS (98.72 %). The in vitro cell assay showed that IC50 values of HES, HAS and HBS on the inflammatory factor NO were 14.5, 14.7 and 13.4 μg/mL, respectively. IC50 values on TNF-α and IL-6 were 21.2, 29.4, 23.9 μg/mL and 8.2, 7.0, 8.7 μg/mL, similarly. The Pharmacological studies showed that PA have obvious anti-inflammatory activity as one of the main effective components of ZB.

Enrichment Extraction and Activity Study of the Different Varieties of Hericium erinaceus against HCT-8 Colon Cancer Cells.

Hericium erinaceus (HE), a widely utilized natural remedy and dietary source, has garnered significant attention for its therapeutic potential in various diseases. In this study, we employed supercritical fluid extraction (SFE) technology to isolate the bioactive compounds from HE's fruiting body. Comprehensive assessments of the antioxidant and antibacterial activities were conducted, along with in vitro investigations on the human colon cancer cell line (HCT-8). The SFE rate served as the evaluation metric, while the variables of extraction time, pressure, and temperature were systematically examined. By integrating the response surface center composite design, we successfully optimized the extraction process, yielding optimal parameters of 80 min, 30 MPa, and 35 °C, thus resulting in an extraction rate of 2.51%. These optimized conditions exhibited considerable antioxidant capacity, anticancer activity, and antibacterial potential. Furthermore, we employed graded alcohol extraction to refine the crude extracts, thereby confirming superior anticancer effects under a 70% alcohol precipitation. To elucidate the composition, Fourier-transform infrared spectroscopy (FT-IR) and gas chromatography-mass spectrometry (GC-MS) were employed to analyze the crude extracts and isolates of HE, facilitating a comparative analysis of six HE varieties. Our findings suggest that sterol derivatives hold promise as the active component against the colon cancer HCT-8 cell line. In conclusion, this study underscores the potential of HE SFE in the development of functional foods or alternative drugs for colon cancer treatment, thus opening new avenues for therapeutic interventions.

Technoeconomic analysis of supercritical fluid extraction process for recycling rare earth elements from neodymium iron boron magnets and fluorescent lamp phosphors

This study offers a comprehensive and rigorous analysis of the technoeconomics of supercritical fluid extraction (SCFE) technology as applied to the recovery of rare earth elements (REEs) from end-of-life neodymium iron boron magnets and fluorescent lamp phosphors. Drawing on an array of data sources including laboratory results, literature data, scaling models, scenario analysis, and sensitivity analysis, this study conducts a sound economic analysis of the SCFE process at an industrial scale. The study renders a detailed estimation of the costs and revenues associated with the process and identifies the primary factors that impact its profitability. The findings demonstrate that the SCFE of REEs from these feedstocks can be economically viable under certain circumstances, with the efficiency of extracting terbium, dysprosium, and neodymium and the price of their respective oxides emerging as key drivers of profitability. By providing valuable insights into the feasibility of the SCFE process for REEs recovery, this study informs future research and development activities in the field.

Evaluation of Biocompatibility of New Osteoplastic Xenomaterials Containing Zoledronic Acid and Strontium Ranelate

Background. The problem of improving the functional characteristics of implanted devices and materials used in traumatology and orthopedics is a topical issue.
 Aim of the study to study biocompatibility of bovine bone matrix xenomaterials modified by zoledronic acid and strontium ranelate when implanted into the bone defect cavity.
 Methods. The study was performed on 24 male rabbits of the Soviet Chinchilla breed. Test blocks of bone matrix were implanted into the cavity of bone defects of the femur. Group 1 animals (n = 8, control group) were implanted with bone xenogenic material (Bio-Ost osteoplastic matrix). Group 2 animals (n = 8) were implanted with bone xenogenic material impregnated with zoledronic acid. Group 3 animals (n = 8) were implanted with bone xenogeneic material impregnated with strontium ranelate. Supercritical fluid extraction technology was used to purify the material and impregnate it with zoledronic acid and strontium ranelate. Radiological, pathomorphological, histological and laboratory (hematology and blood biochemistry) diagnostic methods were used to assess biocompatibility. Follow-up period was 182 days after implantation.
 Results. It was found out that on the 182nd day after implantation the median area of the newly-formed bone tissue in the defect modeling area in Group 1 was 79%, in Group 2 0%, in Group 3 67%. In Group 2 the maximum area by this period was filled with connective tissue 77%. Median relative area of implanted material fragments in Group 1 was 4%, in Group 2 23%, in Group 3 15%. No infection or material rejection was observed in animals of all groups. There were no signs of intoxication or prolonged systemic inflammatory reaction. Laboratory parameters did not change significantly over time. One animal in each group experienced one-time increase in C-reactive protein level against the background of leukocytosis. Two animals in Group 1 had a slight migration of implanted material under the skin, one animal developed arthritis of the knee joint.
 Conclusion. Osteoplastic materials based on bovine bone xenomatrix and filled with zoledronic acid and strontium ranelate have acceptable values of biocompatibility including their safety profile.

Liver Protection of a Low-Polarity Fraction from Ficus pandurata Hance, Prepared by Supercritical CO2 Fluid Extraction, on CCl4-Induced Acute Liver Injury in Mice via Inhibiting Apoptosis and Ferroptosis Mediated by Strengthened Antioxidation

Ficus pandurata Hance (FPH) is a Chinese herbal medicine widely used for health care. This study was designed to investigate the alleviation efficacy of the low-polarity ingredients of FPH (FPHLP), prepared by supercritical CO2 fluid extraction technology, against CCl4-induced acute liver injury (ALI) in mice and uncover its underlying mechanism. The results showed that FPHLP had a good antioxidative effect determined by the DPPH free radical scavenging activity test and T-AOC assay. The in vivo study showed that FPHLP dose-dependently protected against liver damage via detection of ALT, AST, and LDH levels and changes in liver histopathology. The antioxidative stress properties of FPHLP suppressed ALI by increasing levels of GSH, Nrf2, HO-1, and Trx-1 and reducing levels of ROS and MDA and the expression of Keap1. FPHLP significantly reduced the level of Fe2+ and expression of TfR1, xCT/SLC7A11, and Bcl2, while increasing the expression of GPX4, FTH1, cleaved PARP, Bax, and cleaved caspase 3. The results demonstrated that FPHLP protected mouse liver from injury induced by CCl4 via suppression of apoptosis and ferroptosis. This study suggests that FPHLP can be used for liver damage protection in humans, which strongly supports its traditional use as a herbal medicine.

Optimization of fucoxanthin extraction obtained from natural by-products from Undaria pinnatifida stem using supercritical CO2 extraction method.

In the recent years, edible brown seaweed, Undaria pinnatifida, has presented beneficial effects, which may be correlated with this species containing major bioactive compounds, such as carotenoids, fatty acids, and phytosterols. Marine carotenoid fucoxanthin is abundantly present in edible Undaria pinnatifida and features strong bioactive activities. The stem of Undaria pinnatifida is very hard to gnaw off and cannot be swallowed; therefore, it is usually discarded as waste, making it an environmental issue. Hence, making full use of the waste stem of Undaria pinnatifida is an urgent motivation. The present study aims to explore the optimal preparation technology of fucoxanthin from Undaria pinnatifida stems using supercritical carbon dioxide methods and provides approaches for the extraction and preparation of bioactive compounds from a waste seaweed part. With the comprehensive optimization conditions applied in this study, the experimental yield of fucoxanthin agreed closely with the predicted value by > 99.3%. The potential of α-amylase and glucoamylase to inhibit bioactive compounds was evaluated. The results demonstrated that the inhibition activity (IC50 value) of α-amylase (0.1857 ± 0.0198 μg/ml) and glucoamylase (0.1577 ± 0.0186 μg/ml) varied with extraction conditions due to the different contents of bioactive components in the extract, especially fucoxanthin (22.09 ± 0.69 mg/g extract). Therefore, this study confirmed supercritical fluid extraction technology to be a useful sample preparation method, which can effectively be used to prepare fucoxanthin from waste marine resources. This method can potentially be applied in functional food and related industries.

Assessing of the most appropriate biotechnological strategy on the recovery of antioxidants from beet wastes by applying the life cycle assessment (LCA) methodology

The valorization of agro-industrial waste streams and residues for the production of antioxidant compounds is a good strategy for circular economy approaches. However, to demonstrate its suitability and operational feasibility, it is necessary to develop environmental assessments to ensure the effectiveness of the production strategy. In this sense, a large-scale simulation has been developed, obtaining ten different scenarios in which both leaves and steam residues are used as process inputs, and five different extraction techniques are applied, both conventional: Soxhlet and maceration, and emerging technologies: ultrasonic assisted extraction (UAE), supercritical fluid extraction (SFE) and pressurized liquid extraction, (PLE). Environmental results have shown that SFE and PLE technologies have the lowest environmental burdens, while UAE has the worst profile due to high energy demand. Electricity could be considered as the main hotspot with the highest impact, followed by steam requirements and the use of extraction solvent. To improve the environmental profile, sensitivity analyses were performed, considering the use of renewable resources for the production of the energy requirements and the selection of the extraction solvent. Although significant improvements were obtained when electricity and steam production is based on hydropower and waste incineration, the environmental profile did not improve when considering ethanol: water mixture or hexane for extraction. Future research should focus on reducing energy requirements and optimizing the solvent dosage for the extraction process.

Risk analysis of a supercritical fluid extraction plant affected by a gas release using a commercial software

This work presents a risk analysis of a plant that uses supercritical fluid extraction technology with carbon dioxide as a solvent to obtain bioproducts from microalgae.Given the high pressure at which it operates, the extraction plant called Luwar could be affected by dangerous events, such as the gas release in concentrations that are harmful to human health. In order to limit the damage, the risk analysis is of primary importance.The gas release could occur following the breakage of a pipe, which was the scenario being considered. It was analyzed using the commercial software Phast & Safeti, an alternative tool to the methods traditionally used in the literature in hazard events of this type, such as the Threshold Limit Value-Time Weighted Average (TLV-TWA) and the Threshold Limit Value-Short Term Exposure Limit (TLV-STEL), that are defined on the basis of the characteristics of the substance dispersed in the air.Since the pressure of the extraction vessel is the highest in the system, the risk analysis was carried out on the breakage of a pipe coming out of the extractor. The results obtained made it possible to identify the risk parameters on the basis of which to make the best choices in terms of safety to cope with the type of hazard analyzed.

Valorization of byproducts from tropical fruits: A review, Part 2: Applications, economic, and environmental aspects of biorefinery via supercritical fluid extraction.

The global trade of tropical fruits is expected to increase significantly in the coming years. In 2018, the production was approximately 100 million tones, an increase of 3.3% compared to the previous year. Nevertheless, according to the Food and Agricultural Organization, every year one-third of the food produced in the world for human consumption is lost or wasted. More specifically, around 45% of the fruits, constituted mainly by peels, seeds, and pulps after juice extraction, are discarded mainly in the agricultural and processing steps. Therefore, decreasing and/or using these byproducts, which are often rich in bioactive components, have become an important focus for both the scientific community and the fruit processing industry. In this line, supercritical fluid extraction (SFE) technology is expected to play a significant role in the valorization of these byproducts. This review presents the concepts of a tropical fruit biorefinery using supercritical CO2 extraction and the potential applications of the isolated fractions. There is a specific focus on the extraction of bioactive compounds, that is, carotenoids and phenolics, but also oils and other valuable molecules. Moreover, the techno-economic and environmental performance is assessed. Overall, the biorefinery of tropical fruits via SFE provides new opportunities for development of food and pharmaceutical products with improved economic and environmental performance.

The Application of Supercritical Fluids Technology to Recover Healthy Valuable Compounds from Marine and Agricultural Food Processing By-Products: A Review

Food by-products contain a remarkable source of bioactive molecules with many benefits for humans; therefore, their exploitation can be an excellent opportunity for the food sector. Moreover, the revalorization of these by-products to produce value-added compounds is considered pivotal for sustainable growth based on a circular economy. Traditional extraction technologies have several drawbacks mainly related to the consumption of hazardous organic solvents, and the high temperatures maintained for long extraction periods which cause the degradation of thermolabile compounds as well as a low extraction efficiency of desired compounds. In this context, supercritical fluid extraction (SFE) has been explored as a suitable green technology for the recovery of a broad range of bioactive compounds from different types of agri-food wastes. This review describes the working principle and development of SFE technology to valorize by-products from different origin (marine, fruit, vegetable, nuts, and other plants). In addition, the potential effects of the extracted active substances on human health were also approached.

The extraction of natural essential oils and terpenoids from plants by supercritical fluid

In order to provide guidance for the improvement of supercritical fluid extraction technology in the extraction of natural volatile oil and terpenoids from plants, SFE was compared with steam distillation, solvent extraction, Soxhlet extraction, pressure method and other traditional extraction processes, and the supercritical CO2 extraction conditions of SFE in the extraction of natural volatile oil and terpenoids were studied, including temperature, pressure, extraction time, extraction time, extraction time, extraction time, extraction time, extraction time and so on. The influence of entrainer or co extractant on the extraction effect was discussed to provide optimization parameters for the extraction process of natural volatile oil and terpenoids. SFE technology has advantages in the extraction of natural plant volatile oil and has broad application prospects in industrial production.

Valorization of Tropical Biomass Waste by Supercritical Fluid Extraction Technology

The inception of sustainable and cleaner extraction technology has paved the way for the innovative development of nonconventional extractions, such as supercritical fluid extraction, apart from conventional extraction counterparts. The concept of biomass waste-to-wealth for the conversion of biomass waste or by-products into value-added products for diversified applications had piqued the prominent interest of researchers and industry players, especially with the abundance of biomass resources readily available in tropical regions that have yet to be tapped into to reach their full potential. In this paper, a critical review of the developments of supercritical fluid technology from its initial inception up to commercialized scalability, including its limitations, extraction of potential tropical biomass wastes for various types of applications, such as biopesticides, bio-repellents, phenolics, and lipids for biofuel, and its role in circular bioeconomy and sustainable development approaches, are discussed in detail.

Supercritical Extraction of Red Propolis: Operational Conditions and Chemical Characterization.

The objective of this study was to determine the best operational conditions for obtaining red propolis extract with high antioxidant potential through supercritical fluid extraction (SFE) technology, using carbon dioxide (CO2) as the supercritical fluid and ethanol as the cosolvent. The following parameters were studied: overall extraction curve, S/F (mass of CO2/mass of sample), cosolvent percentage (0, 1, 2 and 4%) and global yield isotherms as a function of different pressures (250, 350 and 450 bar) and temperatures (31.7, 40 and 50 °C). Within the investigated parameters, the best conditions found were an S/F of 131 and the use of ethanol at the highest concentration (4% w/w), which resulted in higher extract yields and higher content of antioxidant compounds. Formononetin, the main biomarker of red propolis, was the compound found at the highest amounts in the extracts. As expected, the temperature and pressure conditions also influenced the process yield, with 350 bar and 40 °C being the best conditions for obtaining bioactive compounds from a sample of red propolis. The novel results for red propolis found in this study show that it is possible to obtain extracts with high antioxidant potential using a clean technology under the defined conditions.

Rana chensinensis Ovum Oil Based on CO2 Supercritical Fluid Extraction: Response Surface Methodology Optimization and Unsaturated Fatty Acid Ingredient Analysis.

Rana chensinensis ovum oil (RCOO) is an emerging source of unsaturated fatty acids (UFAs), but it is lacking in green and efficient extraction methods. In this work, using the response surface strategy, we developed a green and efficient CO2 supercritical fluid extraction (CO2-SFE) technology for RCOO. The response surface methodology (RSM), based on the Box–Behnken Design (BBD), was used to investigate the influence of four independent factors (pressure, flow, temperature, and time) on the yield of RCOO in the CO2-SFE process, and UPLC-ESI-Q-TOP-MS and HPLC were used to identify and analyze the principal UFA components of RCOO. According to the BBD response surface model, the optimal CO2-SFE condition of RCOO was pressure 29 MPa, flow 82 L/h, temperature 50 °C, and time 132 min, and the corresponding predicted optimal yield was 13.61%. The actual optimal yield obtained from the model verification was 13.29 ± 0.37%, and the average error with the predicted value was 0.38 ± 0.27%. The six principal UFAs identified in RCOO included eicosapentaenoic acid (EPA), α-linolenic acid (ALA), docosahexaenoic acid (DHA), arachidonic acid (ARA), linoleic acid (LA), and oleic acid (OA), which were important biologically active ingredients in RCOO. Pearson correlation analysis showed that the yield of these UFAs was closely related to the yield of RCOO (the correlation coefficients were greater than 0.9). Therefore, under optimal conditions, the yield of RCOO and principal UFAs always reached the optimal value at the same time. Based on the above results, this work realized the optimization of CO2-SFE green extraction process and the confirmation of principal bioactive ingredients of the extract, which laid a foundation for the green production of RCOO.

Clean Technologies for Obtaining Biocomposites of Brazilian Ginseng Pfaffia glomerata (Spreng.) Pedersen: A Review

The Brazilian ginseng Pfaffia glomerata (Spreng.) Pedersen belongs to the Amaranthaceae family and has as its main component β-ecdysone, a phytoecdysteroid, found in the roots, stem, flowers and leaves of the plant. In the last years sustainability and the environment concern were decisive for the emerging supercritical fluid extraction and pressurized fluid extraction technologies to obtain biocomposites from the plant. These extraction technologies use solvents (CO2, ethanol and water) and uses as controllable parameters pressure, flow, time and temperature. The combination of these factors generates atoxicity, no residue in the final extract and have a reduced energy cost and an excellent extraction yield. This work reviews the literature from 2007 to 2020 on the use of clean technology to obtain chemical biocomposites of interest in the areas of biology, agronomy, food and pharmaceutics. It is was concluded that the supercritical fluid extraction and pressurized liquid extraction extracts were very efficient in obtaining β-ecdysone, since both presents low energy consumption, uses environmentally correct solvents which reduces harmful effects on the environment. Finally, to choose the best technology for extraction of other biocomposites depends on the chemical compound of interest.

Croton tiglium essential oil compounds have anti-proliferative and pro-apoptotic effects in A549 lung cancer cell lines.

As a traditional Chinese medicine, Croton tiglium has the characteristics of laxative, analgesic, antibacterial and swelling. This study aimed to analyze the chemical composition of C. tiglium essential oil (CTEO) extracted from the seeds of C. tiglium and its cytotoxicity and antitumor effect in vitro. Supercritical CO2 fluid extraction technology was used to extract CTEO and the chemical constituents of the essential oil were identified by comparing the retention indices and mass spectra data taken from the NIST library with those calculated based on the C7-C40 n-alkanes standard. In vitro cytotoxicity of the CTEO was assessed against cancer cell lines (A549) and the human normal bronchial epithelial cells (HBE) using the CCK-8 assay. Proliferation was detected by colony formation experiments. Wound scratch and cell invasion assays were used to detect cell migration and invasion. Levels of apoptotic markers, signaling molecules, and cell cycle regulators expression were characterized by Western blot analysis. As the results, twenty-eight compounds representing 92.39% of the total oil were identified in CTEO. The CTEO has significant antitumor activity on A549 cancer cells (IC50 48.38 μg/mL). In vitro antitumor experiments showed that CTEO treatment significantly inhibited the proliferation and migration of A549 cells, disrupted the cell cycle process, and reduced the expression levels of cyclin A, cyclin B and CDK1. CTEO can also reduce mitochondrial membrane potential, activate caspase-dependent apoptosis pathway, and finally induce apoptosis. CTEO may become an effective anti-cancer drug and will be further developed for cancer treatment.

Effect of supercritical CO2 extraction variability on the yield of Tridax procumbens roots extract and (3S)-16,17-didehydrofalcarinol content

Currently, no studies have reported the application of supercritical fluid extraction (SFE) to obtain extracts of Tridax procumbens roots and to evaluate the effects of the pressure, temperature, and extraction time variables. There are few analytical investigations that have been done for the quantitation of falcarinol-type molecules in this species. In this study, a fast, new method using the SFE technology for the obtention of CO2 extract of T. procumbens, as well as its active metabolite (3S)-16,17-didehydrofalcarinol, was done. The aim was to evaluate the potential of a SFE procedure to deliver a high yield in a complex matrix and to achieve the best and selective condition. For the CO2 extract, the highest yield (0.2230 mg/g) was attained when 200 bar, 40 °C, and 4.5 h were employed; on the other hand, the maximum amount of (3S)-16,17-didehydrofalcarinol was 0.0409 mg/g operating at 150 bar, 45 °C, and 1.5 h.

Risk analysis of a supercritical fluid extraction plant using a safety software

The Supercritical Fluid Extraction (SFE) technology is currently used in many industrial fields thanks to the advantages that it can offer. Experimental tests are carried out for different purposes such as decaffeination of coffee/tea, extraction of aromas and herbal flavours as well as spices, extraction of fats and oils, extraction of cholesterol and extraction of alcohol from beverages. SFE plants safety is closely linked to the high pressure they operate, a condition that can lead to a risk status for plant operations and above all workers. For this reason it is necessary to adopt preventive safety measures and a risk analysis is the means that allows to define and examine hazardous scenarios in order to identify safety devices. Risk scenarios related to an extraction plant as explosions are analysed through methods based on indices determination such as the Fire and Explosion Index (F&EI), the Safety Weighted Hazard Index (SW&HI) and the Probit method. This work presents the risk analysis of a SFE plant named “Luwar” using the commercial software “Phast & Safeti” provided by the DNV GL Company. In the plant is used CO2 as extraction fluid and the process purpose is valuable compounds extraction from microalgae. The risk analysis is performed on the extraction vessel considering the plant placed inside a structure (indoor condition). The results allow to identify two risk parameters, i.e. the distance and the area within which CO2 concentration in the air assumes a value considered unsafe for human health. On the basis of the outputs it is possible to identify the safety system to be adopted in order to limit the damage deriving from the occurrence of a risk situation.

Development of heavy oil upgrading technologies in China

Abstract Heavy oils have high viscosity, density, and Conradson carbon residue and high contents of sulfur, nitrogen, oxygen, nickel, and vanadium, as well as asphaltenes, which can cause problems for producers, leading to catalyst deactivation and fouling and plugging of tubing, pipes, valves, and reactor flow lines. Heavy oil upgrading can be classified into carbon rejection and hydrogen addition processes, mainly including four technologies: (1) the fluid catalytic cracking (FCC) process, which catalytically converts heavy oil into light fractions, like liquid petroleum gas, naphtha, and light cycle oil; (2) the hydro-processing process, which catalytically converts heavy oil to high-quality feedstock for FCC and hydrocracking processes under the hydrogen atmosphere without coke formation; (3) the coking process, which thermally converts heavy oil into light liquid fractions and large amounts of coke; and (4) the solvent deasphalting process, which fractionates distillation resid to provide feedstock for residue FCC, such as the residue oil solvent extraction. This paper reviews the progress on basic research of heavy oil chemistry and processing technology developments in China. Heavy oils were comprehensively characterized by the supercritical fluid extraction and fractionation technology and high-resolution mass spectrometry. The FCC process for maximizing iso-paraffin, new residue hydroprocessing technologies, progress in coking process, and a new process – the Supercritical Fluid Selective Extraction Asphaltene Technology – were discussed. As an emerging and promising research area, molecular management techniques were prospected, as well as a new concept of coupling the SELEX-Asp with the conventional heavy oil upgrading processes.

Simulation and techno-economic optimization of the supercritical CO2 extraction of Eucalyptus globulus bark at industrial scale

This work addresses economic and process aspects of the supercritical fluid extraction (SFE) of Eucalyptus globulus bark at industrial scale. Broken plus intact cells (BIC) model was applied to existing data and new SFE curves were simulated. Then, statistical optimization was performed with Response Surface Methodology (RSM) involving of 5 factors (pressure, temperature, cosolvent content, solvent flow rate and extraction time), and four responses: Total Yield (ηTotal), Productivity, Cost of Manufacturing (COM) and Process Energy. The design and simulation of the industrial process (Aspen Plus® software) was performed including the employment of cosolvent in the system. The best COM scored 28.1 € kgextract-1, where ηTotal was 0.84-0.96 wt.%, Productivity reached 311–362 tonextractyear-1, and Process Energy scored 1.46– 2.10 GJ kgextract-1. These results underline that SFE provides an extended margin for trade-offs, and arguments towards the integration of SFE technology to biorefine the bark of E. globulus in pulp mills.