Supercritical fluid extraction and fractionation of natural matter
Ernesto Reverchon ∗, Iolanda De MarcoUniversita di Salerno, Dipartimento di Ingegneria Chimica ed Alimentare, Via Ponte don Melillo, 84084 Fisciano (SA), Italy
Received 30 June 2005; received in revised form 13 March 2006; accepted 13 March 2006
bstract
Supercritical extraction and fractionation of natural matter is one of the early and most studied applications in the field of supercritical fluids. Ihe last 10 years, studies on the extraction of classical compounds like essential and seed oils from various sources: seeds, fruits, leaves, flowerhizomes, etc., with or without the addition of a co-solvent have been published. Supercritical extraction of antioxidants, pharmaceuticals, colourin
atters, and pesticides has also been studied. The separation of liquid mixtures and the antisolvent extraction are other processes that can perform
ery interesting separations. Mathematical modelling has also been developed and refined for some of these processes.The objective of this review is to critically analyze traditional and new directions in the research on natural matter separation by supercritical
Extraction of compounds from natural sources is the mostidely studied application of supercritical fluids (SCFs) with
everal hundreds of published scientific papers. Indeed, super-ritical fluids extraction (SFE) has immediate advantages overraditional extraction techniques: it is a flexible process dueo the possibility of continuous modulation of the solventower/selectivity of the SCF, allows the elimination of pollut-ng organic solvents and of the expensive post-processing of thextracts for solvent elimination.
Several compounds have been examined as SFE solvents.or example, hydrocarbons such as hexane, pentane and butane,itrous oxide, sulphur hexafluoride and fluorinated hydrocar-ons [1]. However, carbon dioxide (CO2) is the most popularFE solvent because it is safe, readily available and has a lowost. It allows supercritical operations at relatively low pressuresnd at near-room temperatures. The only serious drawback ofFE is the higher investment costs if compared to traditionaltmospheric pressure extraction techniques. However, the baserocess scheme (extraction plus separation) is relatively cheapnd very simple to be scaled up to industrial scale.
SFE works have been the subject of several reviews [2–10].herefore, we will limit time interval of our analysis to the lastecade (1996 to present time), presenting first a summary of theoncepts and results that we consider as well established in theiterature [2].
Early works on SFE frequently used high pressures>350 bar) even when relatively supercritical CO2 (SC-CO2)oluble compounds had to be extracted (for example: terpenes,esquiterpenes, fatty acids, etc.). Operating in this manner, onlyhe solvent power of the SCF was enhanced. Then, the concept ofhe optimization between solvent power and selectivity has beenpplied and SFE operating conditions have been chosen to obtainhe selective extraction of the compounds of interest, reducing tominimum the co-extraction of undesired compounds [2]. For
uccessful extraction, not only the solubility of the compounds toe extracted and/or of the undesired compounds has to be takennto account; mass transfer resistances due to the structure of theaw material and to the specific location of the compounds to bextracted can also play a relevant role. A microscopic analysisf the natural structure can help in understanding where massransfer resistances are located. Specific experiments performedarying particle size and supercritical solvent residence time canlso be helpful in this sense. The complex interplay between
hermodynamics (solubility) and kinetics (mass transfer) has toe understood to properly perform SFE.
Fractional separation of the extracts is another well-knownoncept that can be useful to improve the SFE process selectiv-
ty. In several cases, it is not possible to avoid the co-extractionf some compound families (with different solubilities, but alsoith different mass transfer resistances in the raw matter). In
hese cases, it is possible to perform an extraction in successiveteps at increasing pressures to obtain the fractional extraction ofhe soluble compounds contained in the organic matrix, selectedy decreasing solubilities in the supercritical solvent. Fractionaleparation allows the fractionation of the SCF extracts, operatinghe plant with some separators in series at different pressures andemperatures. The scope of this operation is to induce the selec-ive precipitation of different compound families as a functionf their different saturation conditions in the SCF. For example,his procedure has been applied in the SFE of essential oils11–16].
In several cases, the starting material is a liquid mixture. Therocess to be applied is the continuous liquid extraction per-ormed in a packed tower. It is worth of note that, while thextraction from solids is a discontinuous operation, the packedower is capable of continuous steady state operation that allowshe processing of large quantities of liquid mixtures in a rela-ively small apparatus and in a short time.
In some other cases, the material to be treated is a liquid mix-ure that contains solid compounds dissolved in it. The extractionf these compounds from the liquid solution cannot be per-ormed in a packed tower since the solid matter will precipitaten the packings and fixed bed extraction is not possible. In thisase, a supercritical antisolvent extraction (SAE) process has toe adopted. The pre-conditions to apply antisolvent extractionre similar to the ones characteristics of supercritical antisolventicronization (SAS): the liquid solvent has to be very soluble inC-CO2, whereas, the solids have to be completely not soluble
n the SCF. The scope of the process is not the micronization,ut the selective extraction of the solid compounds. These condi-ions can be frequently obtained since many organic solvents areeadily soluble in SC-CO2 even at mild operating conditions andany high molecular weight solids show negligible solubilities
n SC-CO2 especially at low CO2 densities.Due to the structural complexity and variability (with the sea-
on, kind, crop, etc.) of the materials to be treated and to the largeariety of compounds that can be extracted (different moleculareight, polarity, link with the structure, etc.), these processes
re far from to be considered exhaustively studied, though somendustrial applications have been already developed. Moreover,n increasing interest has been registered in the extraction of highdded value substances, such as antioxidants, pharmaceuticals
E. Reverchon, I. De Marco / J. of Supercritical Fluids 38 (2006) 146–166 147
nd colouring matters.Therefore, the scope of this review is to analyze SFE, SAE
nd liquid fractionation studies performed in the last 10 years,onsidering the evolution of the extraction processes, products
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nd materials treated. A critical analysis will be performed andhe perspectives of the field will be illustrated.
. Solids processing
It is the most studied SCF application since the most fre-uently required separation process is the extraction/eliminationf one or more compound families from a solid natural matrix.he basic extraction scheme consists of an extraction vesselharged with the raw matter to be extracted. As a rule, thetarting material is dried and grinded to favour the extractionrocess. It is loaded in a basket located inside the extractorhat allows fast charge and discharge of the extraction vessel.he SCF at the exit of the extractor flows through a depres-urization valve to a separator in which, due to the lower pres-ure, the extracts are released from the gaseous medium andollected.
More sophisticated extraction schemes contain two or moreeparators. In this case, it is possible to fractionate the extract inwo or more fractions of different composition by setting oppor-une temperatures and pressures in the separators [17–34]. Solidsre-processing is also a parameter that can largely influencehe separation performance. For example, solid drying, flak-ng and particle size optimization have, as a rule, be taken intoccount.
Other possible variations of the SFE processing scheme are:ultistage extraction and co-solvents addition. Multi-step oper-
tion is obtained varying pressure and/or temperature in eachrocess step [35,36]. This strategy can be used when it is requiredhe extraction of several compound families from the same
atrix and they show different solubilities in SC-CO2. It takesdvantage of the fact that SC-CO2 solvent power can be con-inuously varied with pressure and temperature. For example,t is possible to perform a first extraction operating at low CO2ensity (e.g., 0.29 g/cm3, 90 bar, 50 ◦C) followed by a secondxtraction step at high CO2 density (e.g., 0.87 g/cm3, 300 bar,0 ◦C). The most soluble compounds are extracted during therst step (for example, essential oils) and the less soluble in theecond one (e.g., antioxidants) [37–40].
A liquid co-solvent can be added to SC-CO2 to increase itsolvent power towards polar molecules. Indeed, SC-CO2 is aood solvent for lipophilic (non-polar) compounds, whereas, itas a low affinity with polar compounds. Various authors addedmall quantities of liquid solvents (for example, ethyl alcohol)hat are readily solubilized by SC-CO2. When in solution, they
odify the solvent power of SC-CO2 [28,32,40–75]. This strat-gy has the drawback that, a larger solvent power could alsoean lower process selectivity and since, as a rule, the co-
olvent is liquid at atmospheric pressure, it will be collectedn the separator together with the extracted compounds. Subse-uent processing for solvent elimination is required; therefore,ne of the advantages of the SFE; i.e., solventless operation isost. Another possible process arrangement is the continuous
eeding and discharging of the solid to obtain the continuousrocessing of the solid matter [76]. This operation is possibledding two solid extruders at the top and at the bottom of thextractor and can avoid the use of two or more extractors to simu-
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ate continuous solid processing; however, design and operationf the two extruders is not cheap and simple.
.1. Selection of the operating parameters
The selection of the operating conditions depends on the spe-ific compound or compound family to be extracted. Moleculareight and polarity have to be taken into account case by case;ut some general rules can be applied. First of all, SFE temper-ture for thermolabile compounds has to be fixed between 35nd 60 ◦C; e.g., in the vicinity of the critical point and as lows possible to avoid degradation. The increase of temperatureeduces the density of SC-CO2 (for a fixed pressure) thus reduc-ng the solvent power of the supercritical solvent; but it increaseshe vapor pressure of the compounds to be extracted. Therefore,he tendency of these compounds to pass in the fluid phase isncreased. However, the most relevant process parameter is thextraction pressure that can be used to tune the selectivity of theCF. The general rule is: the higher is the pressure, the larger
s the solvent power and the smaller is the extraction selectiv-ty. Frequently, the solvent power is described in terms of theC-CO2 density at the given operating conditions. CO2 densityan vary from about 0.15 to 1.0 g/cm3 and is connected to bothressure and temperature. Its variation is strongly non-linear;herefore, the proper selection requires the use of accurate tablesf CO2 properties [77,78].
The other crucial parameters in SFE are CO2 flow rate, par-icle size of the matrix and duration of the process (extractionime). The proper selection of these parameters has the scopef producing the complete extraction of the desired compoundsn the shorter time. They are connected to the thermodynamicssolubility) and the kinetics of the extraction process in the spe-ific raw matter (mass transfer resistances). The proper selectionepends on the mechanism that controls the process: the slow-st one determines the overall process velocity. CO2 flow rates a relevant parameter if the process is controlled by an exter-al mass transfer resistance or by equilibrium: the amount ofupercritical solvent feed to the extraction vessel, in this case,etermines the extraction rate. Particle size plays a determiningole in extraction processes controlled by internal mass transferesistances, since a smaller mean particle size reduces the lengthf diffusion of the solvent. However, if particles are too small,hey can give problems of channelling inside the extraction bed.art of the solvent flows through channels formed inside thextraction bed and does not contact the material to be extractedhus causing a loss of efficiency and yield of the process. As
rule, particles with mean diameters ranging approximatelyetween 0.25 and 2.0 mm are used. The optimum dimensionan be chosen case by case considering water content in theatrix and the quantity of extractable liquid compounds that
an produce phenomena of coalescence among the particleshus favouring the irregular extraction along the extraction bed.
oreover, the production of very small particles by grinding
ould produce the loss of volatile compounds. Process durations interconnected with CO2 flow rate and particle size and haso be properly selected to maximize the yield of the extractionrocess.
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.2. Examples of application
Some well established industrial processes use SFE to pro-uce hops extracts, decaffeinated coffee and some food nutri-ional substances that offer also some aspects of therapeuticrotection to the human body (nutraceuticals). However, manyther applications are possible.
.2.1. Essential oils extraction/isolationThis process has been widely studied. Essential oils are
ainly formed by hydrocarbon and oxygenated terpenes andy hydrocarbon and oxygenated sesquiterpenes. They can bextracted from seeds, roots, flowers, herbs and leaves using theo-called hydrodistillation. This is a very simple process, butuffers of many drawbacks: thermal degradation, hydrolysis andolubilization in water of some compounds that alter the flavournd fragrance profile of many essential oils extracted by thisechnique.
From the point of view of SFE, essential oils isolation is anxample of extraction plus fractional separation. Indeed, thisrocess can be optimally performed operating at mild pres-ures (from 90 to 100 bar) and temperatures (from 40 to 50 ◦C)ince at these process conditions all the essential oil componentsre largely soluble in SC-CO2 [79–82]. For example, linalool,typical oxygenated terpene is completely miscible with SC-O2 at pressures larger than about 85 bar when the temperature
s set at 40 ◦C [83]. Essential oils are at least partly locatednside the vegetable structure; therefore, mass transfer resis-ances have to be considered too. At the previously discussedperating conditions, essential oil components are extractedogether with cuticular waxes; i.e., paraffinic compounds locatedn the surface of vegetable matter with the scope of control-ing perspiration. Paraffins exhibit a relatively low solubility athese operating conditions [84]; but, of course, if the extrac-ion pressure is increased their contribution in the extract wille more relevant; other compounds (like fatty acids) could belso increasingly extracted. Therefore, extraction of waxes isontrolled by their solubility and essential oil extraction is con-rolled, at least in part, by internal mass transfer resistances inhe vegetable structure. As a result of these interactions, the twoompound families (essential oil and waxes) are co-extracted atll operating conditions. To selectively extract the essential oillone, it is necessary to take advantage of the fact that at lowemperatures (from −5 to +5 ◦C) waxes are practically insolu-le in CO2, whereas, the other compounds maintain very largeolubilities. Therefore, it is possible to fractionate the extractperating, for example, the extraction at 90 bar, 40 ◦C and, then,erforming a first separation, for example, at 0 ◦C, 90 bar, andsecond separation at 15 ◦C and 20 bar. In this manner, in therst separator the selective precipitation of waxes is obtainednd no precipitation of the other extracted compounds occurs,hereas, in the second separator, essential oil is recovered. An
ndustrial plant (V = 1200 dm3) that uses this process arrange-
ent has been constructed and successfully operated (Essences,
taly). It is not possible to perform the extraction directly at 0 ◦Cnd 90 bar, since the vegetable matter contains many other com-ound families (antioxidants, colours, etc.) that are soluble at
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hese process conditions and, therefore, a complex mixture ofssential oil plus these other compounds is obtained.
Data on essential oils supercritical extraction is shown inable 1 that is alphabetically organized by the common nameraw material), the botanical name and the target component (thextract). In Table 1, laboratory, pilot plant and analytical stud-es performed using very small extractors are included. Only inome of them, the operating conditions have been optimized toaximize both the total yield and the selectivity of the process;
herefore, yield and the operating conditions can be largely influ-nced by the final scope of the paper: to selectively obtain thessential oil, or to extrapolate its composition from the unfrac-ionated extract (“concrete”). An analysis on the influence ofome process parameters such as pressure, temperature, extrac-ion time, percentage of co-solvents and solvent flow rates isvailable in some of the papers considered in Table 1.
.2.2. Seed oils extractionVegetable oil from seeds is traditionally produced by hex-
ne extraction from ground seeds. The process is very efficient,ut its major problem is represented by hexane elimination afterxtraction. Three distillation units in series, operated under vac-um and other ancillary apparatuses (deodorizer, degumming,tc.), have to be used. The possible thermal degradation of the oilnd the incomplete hexane elimination (from 500 to 1000 ppmesidue) are the drawbacks of this process. Therefore, severaluthors have proposed the substitution of the traditional processy SC-CO2 extraction of oil from seeds [22,28,41,68,71,85–89]see Table 1). Indeed, triglycerides forming seed oils are read-ly soluble in SC-CO2 at 40 ◦C and at pressures larger thanbout 280 bar. The main parameters to be taken into accountor this process are particle size, pressure and residence time.mall particles (1 mm mean diameter or less) and high pressures300–500 bar) can strongly reduce the extraction time. Afterxtraction, the SC-CO2 tryglicerides solution is sent to a sep-rator working at subcritical conditions. This operation reduceso near zero the solvent power of CO2 and allows the recoveryf oil. The complete elimination of gaseous CO2 from oil is alsobtained in the separator. The SFE of several seed oils has beenuccessfully performed up to the pilot scale.
An alternative process has also been proposed, in which thextraction is performed at a fixed pressure and only tempera-ure variations are used to reduce the oil solubility and obtain itsecovery. The advantage of this scheme coupled to heat exchang-rs networking is in the reduction of energy consumption in theverall extraction process [90].
.3. High added value compounds
The list of high added value compounds (mainly nutraceuti-als and pharmaceuticals) is reported in Table 2. A large spec-rum of compounds can be inserted in these categories, sinceood additives with nutritional and pharmaceutical properties
nutraceuticals) range from tocopherols to carotenoids to alka-oids to unsatured fatty acids. Pharmaceutical compounds likertemisinin (antimalaric drug), to Hyperforin (antidepressantrug), to sterols can be extracted from various matters. Pesticides
150 E. Reverchon, I. De Marco / J. of Supercritical Fluids 38 (2006) 146–166
Table 1SFE of oleoresins (OR), essential (EO), volatile (VO) and seed (SO) oils
Raw material Botanical name Extract References
Anise seeds Pimpinella anisum L. EO [91]Bacuri fruit shells Platonia insignis Mart. EO [92]Basil leaves Ocimum basilicum EO [69,93]Borage seeds Borage officinalis L. SO [41,85]Cashew Anacardium occidentale VO [36,94]Celery roots Apium graveolens L. SO [28,86]Chamomile flowers Chamomilla recutita L. R. EO and OR [95]Clove bud Eugenia caryophyllata EO [19]Coriander seeds Coriandrum satium L. SO [87]Eucalyptus leaves Eucalyptus globulus L. EO [17]Fennel seeds Foeniculum vulgare Mill. SO [22]Grape seeds Vitis vinifera SO [59]Hiprose seeds Rosa canina L. SO [68,88,89]Juniper fruits Juniperus communis L. VO [96]Laurel leaves Laurus nobilis EO [20]Lemon balm Melissa officinalis EO [22,27,97]Lemon bergamot Monarda citriodora EO [97]Lemon eucalyptus Eucalyptus citriodora EO [97]Lemongrass leaves Cymbopogon citrates EO [97,98]Lovage leaves and roots Levisticum officinale Koch. EO [28,69,99,100]Marjoram leaves Origanum majorana EO [101]Mint leaves Mentha spicata insularis EO [21,93]Oregano Origanum vulgare L. EO [67,69,93,102,103]Palm kernel oil Elaeis guineensis SO [104,105,106]Pennyroyal Mentha pulegium L. EO [56]Pepper, black Piper nigrum L. EO [107,108]Pepper, red Capsicum frutescens L. OR [109]Rye bran Secale cereale Alkylresorcinols [73]Sage leaves Salvia desoleana EO [21,69]Spiked thyme Thymbra spicata EO [110]Star anise Illicium anisatum EO [19]Thyme Thyme zygis sylvestris EO [111]TV
r insecticide principles are widely diffused in the vegetableatter and, if extracted by SFE could be used in the biological
griculture.Another kind of extraction process is the elimination of pollu-
ants and pesticides from natural matter in which they obviouslyxert a detrimental effect. These products are outside the scopesf this work; but, they represent another interesting applicationf SFE [65,66,112].
In the following, some relevant cases, that have been recentlytudied, are discussed in the detail.
.3.1. Nutraceuticals: Lycopene and AstaxanthinCarotenoids are a large family of compounds that possess
ntioxidant and colouring properties and are investigated forood, cosmetic and medical applications. They are containedn a large variety of natural sources: vegetables, animals, bac-eria, yeasts, microalgae. Traditional carotenoids extraction iserformed by organic solvents with the well-known problemsf selectivity and organic solvents usage and pollution. Pre-
reatments of the starting material play a relevant role in thefficiency of the extraction process: crushing, freeze drying,nzymatic cell degradation have been proposed. The problems to reduce the internal mass transfer resistance that opposes a
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trong obstacle to extraction, since these materials are very fre-uently located well inside complex cellular structures and canlso be linked to the solid matrix.
Their extraction by SCFs from various sources has beentudied by several authors [25,32,53,63,64,72,118,136,138–40,150,151,164–169]. Depending on the particular compoundtudied (molecular weight and number of polar bounds), theyhow very low or moderate solubilities in SC-CO2. Therefore, ineveral cases SC-CO2 added with a co-solvent has been proposeds the supercritical extraction medium. The most frequently pro-osed co-solvent is ethyl alcohol since its presence (in traces) inhe final extracts does not compromise the use in nutraceuticalr pharmaceutical applications. However, it is better, when it isossible, to avoid the use of a liquid co-solvent that tends toepropose the problem of solvent elimination from the extracts.
Most carotenoids are polyunsaturated hydrocarbons contain-ng 40 carbon atoms and two terminal ring systems. Carotenoidshat are composed entirely of carbon and hydrogen are calledarotenes, whereas, those that also contain oxygen are called
anthopylls.
Lycopene is a carotene with relevant antioxidant propertiesnd can have a protective effect against various chronic illnesseslike coronary heart disease and cancer). The major sources of
E. Reverchon, I. De Marco / J. of Supercritical Fluids 38 (2006) 146–166 151
Table 2SFE of high added value compounds
Raw material Botanical name Extract References
Aloe vera leaves Aloe barbadensis Miller �-Tocopherol [51]Animal liver Benzimidazoles [113]Anise verbena Lippia alba Limonene and carvone [114,115]Apricot pomace Prunus armeniaca �-Carotene [72]Artemisia Artemisia annua L. Artemisinin [116]Boldo leaves Peamus boldus M. Boldine [44,117]Bupleuri radix Bupleurum kaoi Liu Saikosponins [31]Buriti fruit Mauritia flexuosa Carotenoids and lipids [118]Cape ash Ekebergia capensis Sparrm. Oleanolic acid and 3-epioleanolic
Feverfew Tanacetum parthenium Parthenolide [129]Fresh bay Laurus nobilis Tocopherol [127]Ginger Zingiber officinale Roscoe Gingerols and shogaols [46,47]Ginkgo Ginkgo biloba L. Ginkgolides and flavonoids [60,70]Green tea Cratoxylum prunifolium Catechins [58]Guarana seeds Paullinia cupana Caffeine [53,130]Hawthorn Crataegus sp. Flavonoids and terpenoids [54]Horsetail Equisetum giganteum L. Oleoresin [131]Indian almond leaves Terminalia catappa L. Squalene [132,133]Kava roots and steams Piper methysticum Lactones [62]Marigold Calendula officinalis Flavonoids and terpenoids [54]Marjoram Origanum majorana L. Carotenoids and chlorophylls [25]Marjoram Origanum majorana L. Phenolic and Triterpenoid
antioxidants[134,135]
Mate leaves Ilex paraguariensis Caffeine, Vitamine E,theobromine and stigmasterol
[53,136]
Mexican sunflower Tithonia diversifolia Tagitinin C [137]Microalgae Botryococcus braunii Alkadienes [138]Microalgae Chlorella vulgaris Canthaxanthin and Astaxanthin [138]Microalgae Nannochloropsis gaditana Carotenoids and chlorophyll [139]Microalgae Spirulina maxima Carotenoids and fatty acids [140]Microalgae Dunaliella salina �-Carotene [138]Microalgae Arthrospira maxima �-Linolenic acid [138]Microalgae Haematococcus pluvialis Astaxantine and phycocyanine [141]Milk Thistle Silybum marianum Tocopherol [142]Moso-Bamboo Phyllostachys heterocycla Ethoxyquin A, sesquiterpene A
and cyclohexanone A[52]
Moutan Paeonia suffruticosa Paeonol [143]Neem seeds Azadirachta indica A. Juss Nimbin, salannin and
azadirachtin[144–147]
Olive leaves Olea europa Polyphenols [43]Olive tree leaves Olea europa Tocopherol [148]Onion Allium cepa L. Onion flavour [24]Pandanus mealybug Pandanus amaryllifolius
Roxb.2-Acetyl-1-pyrroline [149]
Paprika Capsicum annuum L. Carotenoids, tocopherols andcapsaicinoids
[150,151]
Parsley Petroselinum crispum Tocopherol [127]
152 E. Reverchon, I. De Marco / J. of Supercritical Fluids 38 (2006) 146–166
Table 2 (Continued )
Raw material Botanical name Extract References
Poultry feed, eggs and muscle tissue Nicarbazin [152]Propolis Resina propoli Flavonoids, galangin and caffeic
acid phenethyl ester[30]
Pyrethrum flower Chrysanthemumcinerariifolium
Pyrethrins [33,34,153]
Red grape pomace Vitis vinifera Agiorgitiko Phenolic antioxidants [154]Red yeast Phaffia rhodozyma Astaxanthin [64]Rice Tocopherols, tocochromanols and
oryzanols[155]
Rosemary Rosmarinus officinalis L. Rosmanol, carnosic acid andcarnosol
[37–39,42,47,156–159]
Sage Salvia officinalis L. Carnosolic acid [29]Savory Satureja hortensis L. Oil [26]Saw Palmetto berries Serenoa repens Fatty acids and �-sitosterol [62]Sesame seeds, black Sesamum indicum L. Sesamol, sesaminol and
�-tocopherol[160,161]
Soybean flour Glycine max Isoflavones [50]Soybean lecithin Glycine max Phosphatidylcholine [74,75]Spearmint Mentha spicata Tocopherol [127]St. John’s Wort Hypericum perforatum L. Hyperforin [162,163]St. John’s Wort Hypericum perforatum L. Phloroglucinols [57]St. John’s Wort flowers Hypericum perforatum L. Hyperforin and Adhyperforin [62]Stevia leaves Stevia rebaudiana Bertoni Glycosides [49]Stinging nettle Urtica dioica L. Carotenoids and chlorophylls [63]Sweet grass Hierochloe odorata 5,8-Dihydroxycoumarin and
5-hydroxy-8-O-�-d-glucopyranosyl-benzopyranone
[40]
Tomato Lycopersicon esculentum Lycopene [32,16,46,162]Tomato Lycopersicon esculentum Lycopene and �-carotene [167–169]Turmeric Curcuma longa L. Curcumin and curcuminoids [47,48]Wheat germ Triricum aestivum Vitamin E [170]W
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ycopene are ripe tomatoes, tomato products and by productsskins). SFE of Lycopene has been performed using pure SC-O2 [164,167] and with co-solvents [32,166,168,169]. The usef appropriate co-solvents (acetone [166], ethanol [169], chlo-oform [168], seed oil [32]) increases the extraction rate but has,s a rule, a negligible influence on the final yield of Lycopene.herefore, using pure SC-CO2 at higher pressures can be suf-cient to compensate the absence of co-solvent and has thedvantage of producing a solvent free extract.
At pressures lower than about 250 bar, operating at 40 ◦C,he extraction of Lycopene is negligible [168]. The yield largelyncreases with pressure due to the increase of Lycopene solubil-ty in the supercritical solvent. From the analysis of the literature,he parameter that mainly controls Lycopene extraction is thextraction temperature. Indeed, several authors [32,165–168]ound a very strong increase of Lycopene yield with temper-ture and decided to operate up to a maximum of 110 ◦C, ashown in Fig. 1 [166]. This effect is surprising since they didot find a similar dependence on temperature for the extraction of-carotene that is also contained in tomato products [167]. Theuthors tried to explain this dependence on temperature con-
idering the increase of SC-CO2 diffusivity with temperaturend an increase of Lycopene vapor pressure; but no explanationeems completely convincing. Lycopene is contained into veg-table structures called chromoplasts in form of large crystals.
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Particle size of the ground matter and supercritical solventow rate are two parameters that can help in understandinghere mass transfer is located (as previously discussed). As a
ule, the decrease of particle size increases the extraction rate;owever, Sabio et al. [167] found a decrease of Lycopene extrac-ion yield at lower particle size and explained (correctly) thisffect with in-homogeneities along the extraction bed due toaking (channelling) of the bed when too small particles weresed.
Of course, Lycopene is not the only compound extracted fromomatoes when a SC-CO2 based solvent is used. �-Carotenend large quantities of lipidic compounds are also co-extracted167]. When compared to organic solvent extraction, the variousuthors found different maximum relative yields in Lycopene,anging from 53.9% [169] to about 80% [167] to almost 90%164] relative yields, the maximum yield being influenced byhe maximum pressure and temperature used.
Astaxanthin is a xanthopyll and its extraction has been pro-osed from various materials as red yeast (Phaffia rhodozyma)64], microalgae (Chlorella vulgaris [138], Haematococcus plu-ialis [141]), crayfish (crustaceous) [125]. The various authorsound that pre-treatments oriented at the decrease of particle sizend/or at the destruction of cell walls are relevant in determin-ng the yield and the extraction rate. Particularly, cell walls oficroalgae have a polymeric structure that strongly obstacles
he extraction of internal compounds [138].The increase of pressure is also relevant in the extraction
fficiency: operation at pressures larger than 200 bar shows aarked increase of extraction rate and yield. Pressures up to
00 bar have been tested, and the maximum yield was identifiedt this pressure value.
The effect of temperature is relatively less relevant and tem-erature higher than 50–60 ◦C are also not indicated to avoidxtract degradation. Ethanol has been used as co-solvent: it ishe only one allowed organic solvent for nutraceutical and phar-
aceutical purposes. Valderrama et al. [141], using pressuresp to 300 bar, found a strong influence of ethanol addition (upo 9.4%) on Astaxanthin extraction. The authors that operatedp to 500 bar found, instead, only a marked influence of the co-olvent (percentages up to 15 vol.%) on the extraction rate [64],ince the solubility of Astaxanthin in SC-CO2 is larger at higherressures and compensates the absence of co-solvent. Super-ritical solvent flow rate showed only a slight influence on thextraction yield.
Considering the results in the overall, it is confirmed thathese processes are conditioned by the internal mass transfer,s suggested by the strong effect of grinding and of the otherre-treatments and by the negligible influence of supercriticalolvent flow rate. The relatively low solubility of Astaxanthinn SC-CO2 also plays a relevant role: high extraction pres-ures are required to obtain a good extraction performance andhe addition of a polar co-solvent increases the extraction rate,ince it increases the solubility of Astaxanthin in the solvent
ixture.Some authors reported a good Astaxanthin extraction yield,
hen compared to its initial content in the matrix (up to 97%)141]; however, the problem of the very large quantity of lipidic
iatc
ritical Fluids 38 (2006) 146–166 153
ompounds co-extracted has not to be underestimated: overallxtraction yields up to 30% (w/w) of the raw material loaded inhe extractor can be obtained, for example, in the case of yeasts.herefore, it is worth of note the indication given by Lim etl. [64] that fractional extraction, performed at two consecutivextraction steps at 300 and 500 bar, can increase the Astaxanthinoncentration in the extracts in the second step up to 10 times;ndeed, most of the undesired compounds have been extracteduring the first extraction step performed at lower pressure, athich Astaxanthin has very low solubility in the supercritical
olvent.
.3.2. Pharmaceuticals: HyperforinSt. John’s wort (Hypericum perforatum) extracts have well
nown antidepressant properties. Despite the evident clinicalffects, there is still a controversy regarding the active princi-le of the extracts. Some authors attribute the antidepressantctivity to Hypericin and its derivatives, whereas, some stud-es support the effect of Hyperforin. However, Hypericin is notxtracted by SC-CO2, even when ethanol is used as co-solvent62]. Rompp et al. [162] tested the extraction of Hyperforin byC-CO2 from plant particles in the pressure range 90–160 bart 40 and 50 ◦C, varying CO2 flow rate and operating at vari-us extraction times. They substantially found that an increasef the extraction pressure leads to a decrease of Hyperforinoncentration in the products, due to an increase of undesiredompounds co-extraction. Moreover, the variation of solventow rate showed no significant effect on the extraction yield andyperforin content, thus confirming that internal mass transfer
ontrols the extraction process.Catchpole et al. [62] performed this extraction using liq-
id CO2, SC-CO2 and SC-CO2 plus ethanol as co-solvent (upo 10 mass%). Using SC-CO2 plus ethanol they obtained anncrease of the total yield with respect to the case of SC-CO2lone (at the same extraction conditions: 300 bar, 40 ◦C) butnly a slight increase of Hyperforin extraction was observed.he comparison of the first separator St. John’s Wort oil yield
n the case of SC-CO2 and liquid CO2 is reported in Fig. 2.About the possibility to extract Hypericin, it should be possi-
le (in principle) to extract this drug using a liquid solvent on theegetable matter and, then, to process the obtained solution byntisolvent extraction. In this case, the liquid solvent is extractednd insoluble Hypericin is precipitated (see for further details inhe chapter on supercritical antisolvent extraction).
.3.3. Pesticides: Pyrethrins and AzadirachtinsPesticides of biological origin are very effective, non-toxic
or warm blood animals and have very short degradation timesn the presence of air and light. An example of plant contain-ng biopesticides is pyrethrum that has a strong action againstnsects and is highly biodegradable. Pyrethrins are the six insec-icide components that form the biopesticide: they are readilyoluble in SC-CO2 even at near critical conditions. Therefore, it
s possible to extract these compounds operating, for example,t 90 bar, 40 ◦C [153]. Higher pressures are not required, sincehey induce the co-extraction of undesidered compounds. Thisoncept is evident in Fig. 3 where it is reported the overall and
154 E. Reverchon, I. De Marco / J. of Superc
Fe
PanTwttoc
eem
Ft
ts[atfl
tAoNtbcybafcbI
tomatAvrt
ig. 2. St. John’s Wort oil yield as a function of CO2 flow rate at two differentxtraction conditions (adapted from [62]).
yrethrins only extraction yield. When a second extraction stept 200 bar and 40 ◦C is performed, the yield of Pyrethrins haso further increase and only undesired compounds are extracted.he fractional separation of the extracts to eliminate co-extractedaxes is, however, required; i.e., the process is very similar to
hat previously described for essential oils isolation. To eliminatehis problem, Kiriamiti et al. [34] proposed a SC-CO2 washingf ungrounded pyrethrum flowers to preliminary extract part ofuticular waxes.
A variation of this process has been proposed by Kiriamitit al. [33] that used as the starting material dried crude hexanextract of pyrethrum flowers that was loaded in the extractorixed with 1 mm glass beads. They obtained the coverage of
ig. 3. Overall extraction yield (squares) and Pyrethrins yield (circles) againsthe extraction time during a multistep extraction (adapted from [153]).
m
2
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stmmt
m((mdpc
ritical Fluids 38 (2006) 146–166
he beads with a film of this material. This process is veryimilar to the extraction of volatile oils from flower concretes11,16,18]. It allows to work with more concentrated samplesnd at controlled conditions inside the extractor. Process condi-ions are similar to those adopted for the extraction from groundowers.
Neem seeds possess a well-known pesticide activity dueo the presence of various active principles collectively calledzadirachtins that are tetranortriterpenoids formed by a groupf closely related isomers such as Salannin, Gemudin andimbin. Nimbin has also several valuable medicinal proper-
ies [144]. The extraction of these principles using SC-CO2 haseen studied by various authors [144–147]. The first step is, ofourse, seeds grinding and pressing to extract the seed oil. Oilields between 25 and 30% (w/w) of the starting material haveeen reported. In this step, small quantities of Azadirachtinsre also extracted. The second step is SFE that can be per-ormed at 250–300 bar and 40–50 ◦C. The SFE product canontain up to 10,000 ppm of Azadirachtins. This process has alsoeen proposed on the industrial scale by Essences srl, Salerno,taly.
Tonthubthimthong et al. [144] concentrated their attentiono Nimbin extraction. Concentration of Nimbin in the extractedil was measured by selectively extracting this compound usingethanol. Some experiments of active principles extraction have
lso been performed adding methanol to SC-CO2 [145,147] inhe attempt to obtain more solvent power towards Azadirachtins.ccording to Johnson and Morgan [147], 20% methanol isery effective in this extraction and reduced pressures withespect to SC-CO2 alone can be used (137 bar). However, Ton-hubthimthong et al. [141] found that methanol is not an effective
odifier for the selective Nimbin extraction.
.4. Mathematical modelling
Mathematical modelling allows a rational approach to thextraction problem, giving the opportunity to generalize thexperimental results, and, if successful, to obtain indicationsbout systems different from those studied (simulation). More-ver, it is useful in the development of scaling-up proceduresrom laboratory to pilot and industrial scales. For these reasonseveral attempts at mathematical modelling of SFE have beenresented in the literature [2,171,172].
A model should not be a mere mathematical instrument, buthould reflect the physical insight arising from the knowledge ofhe solid structure and from experimental observations. Mathe-atical models, which have no physical correspondence to theaterials and the process studied are of limited validity, although
hey can be used to fit some experimental data.Three different approaches have been proposed for the
athematical modelling of SFE: (1) empirical [173,174],2) based on heat and mass transfer analogy [175,176], and3) differential mass balances integration [171,177,178]. The
ost proper analysis is obtained from the integration of the
ifferential mass balances: time dependent concentrationrofiles are obtained for fluid and solid phase. The extractionurve is calculated from the fluid phase concentration at the
E. Reverchon, I. De Marco / J. of Superc
es
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(
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Fig. 4. SEM image of a section of sunflower seed.
xtractor outlet.In facing mathematical modelling of SFE,everal general aspects have to be taken into account:
a) Solid material structureThe knowledge of the botanical aspects and/or optical
microscope or scanning electron microscope (SEM) analy-sis of the material are necessary to visualize its structure. Forexample, seeds are essentially formed by specialized struc-tures that operate as small recipient containing the oil. Theirshape and structure change seed by seed; but the generalorganization is always the same. An example of seed struc-ture observed by SEM is reported in Fig. 4 and evidencesthe typical oil bearing structures in the case of sunflowerseed [35,179].
b) Location of the compounds to be extractedThe distribution of the solute within the solid substrate
may be very different. The extractable substances may befree on the surface of the solid material or inside the struc-ture of the material itself. For example, essential oil can belocated near the leaf surface in glandular trichomes and/orinto vacuoles; i.e., intracellular structures located well insidethe leaf [35,180].
c) Interactions of solutes with the solid matrixDepending on the interactions between the compounds
and the solid structure, different equilibria may be involved.Indeed, if the material has no interactions with matrix, equi-librium solubility has to be taken into account. The materialcan be adsorbed on the outer surface or inside the solid struc-ture. In this case, a partitioning equilibrium between solidand fluid phase will occur.
d) Broken-intact cell structuresPart of the compounds to be extracted may be near the
surface of the structure, due to cell breaking during grind-ing. This case is characteristic of grinded seed particles: anon-negligible part of the oil is free on particles surface.Moreover, membranes modifications may occur due to dry-
ing, freeing part of the soluble material.
e) Shape of particlesParticles may be spherical, plate-like, etc. as a result of the
original shape of the material (for example, leaves) and of
tTtm
ritical Fluids 38 (2006) 146–166 155
the grinding process. Their shape can influence the diffusionof the supercritical solvent [35,171].
From the point of view of the extraction mechanisms, otheronsiderations are necessary. The equilibrium may exist if:
a) the material is largely available;b) it is distributed on or near the surface;c) the kind of equilibrium will depend on the interactions (if
any) with the solid structure.
Mass transfer resistances, in general, may be of two types:xternal or internal (and in this case, various possibilities have toe considered). To take into account mass transfer resistances,ifferential mass balances are applied.
Up to now, mathematical modelling has been mainly appliedo the extraction of seed oils, essential oils or volatile compoundsnd to the adsorption/desorption of terpenic model mixtures181–183], since more data exists in the literature for these pro-esses. Materials for which mathematical modelling of SFE haseen attempted are reported in Table 3. We have also indicated ifhe model is based on empirical kinetic equations, on the anal-gy between heat and mass transfer (HMT) or on differentialass balances integration (DMBI) along the extraction bed or
n a single particle.Reverchon et al. [179,184,190,192] used scanning electron
icroscope to observe broken cells on seed particles surface.hey assumed that broken cells form a single layer, and wereble to calculate volumetric broken-to-intact cell ratio and thuso reduce the number of model parameters to be evaluated fromxtraction curves. The concept of broken and intact cells wasombined with equilibrium relationship for either free solute205,206] or solute interacting with matrix [177,180]. Both typesf equilibrium were also assumed to occur simultaneously byarious authors, the free solute in broken cells and the interact-ng solute in intact cells [179,180,184,190,192]. In one of theseapers [179], an extensive analysis was performed for six seedils extraction using data from literature. The model was firstalidated and then used to simulate several possible cases ofxtraction.
Sovova [172] proposed a general model approach applied toeed oil and essential oil extraction. The model is based on theivision of the process in two extraction periods: the first oneoverned by phase equilibrium and the second one by internaliffusion in particles, taking into account the concept of brokennd intact cells to explain the sudden reduction of the extractionate after the first extraction step. This effect is particularly evi-ent in the case of seed oil extraction. The new feature of theodel is the description of the first extraction period considering
ifferent types of phase equilibria: independent on matrix (sol-bility equilibrium), adsorbed on the matrix (partition betweenhe two phases) and different flow patterns, mainly dispersion.he model has been verified on data sets from literature, related
o seeds (almond) and essential oils (orange peels, pennyroyal).his model presents a limit in the case of essential oils extrac-
ion, when the extractable material is located only inside theatrix: the concept of broken (in the surface) and intact cells
156 E. Reverchon, I. De Marco / J. of Supercritical Fluids 38 (2006) 146–166
Table 3Mathematical modelling of SFE from natural matter
inside the particle) is no more applicable and the first part ofxtraction controlled by equilibrium does not apply.
Gaspar et al. [35] modelled the extraction of oregano essentialil. The model is based on the prevalent geometry of particles:hose obtained from leaves tend to maintain a plate-like geom-try. Mass balances on the particle have been proposed.
Mathematical modelling of SFE has also been proposedor some other materials. Wu and Hou [207], for example,roposed the extraction of egg yolk oil (cholesterol, glyc-rides and moisture) from egg yolk powder with the scopef producing a matrix (solid residue) rich in phospholipidsnd proteins. Optimum extraction conditions were found at5 ◦C and in the pressure range between 280 and 360 bar. Theypplied differential mass balances integration to the egg powderxed bed.
Adsorption–desorption processes can also be treated asxtraction processes: adsorption–desorption isotherms being thequilibrium curves due to interactions of the solutes betweenhe solid matrix and the fluid phase. Differential mass bal-nces also in this case can describe the extraction process.his approach has been used by Reverchon [182] to model the
elective desorption from silica gel of two key compounds ofssential oils: limonene (representative of the hydrocarbon ter-enes fraction) and linalool (representative of the oxygenatederpenes fraction). Then, the model has been extended to the
oaow
ractional desorption of bergamot peel oil [181] describing awo steps desorption process with the first step performed at0 ◦C, 75 bar to desorb hydrocarbon terpenes and the second stept 40 ◦C, 200 bar to desorb the oxygenated compounds. Later,everchon et al. [183] also modelled the selective adsorptionn silica gel of a complex terpenic mixture formed by 13 com-onents. The mixture was divided in four families considereds four pseudo-key components. The integration of differentialass balances gave account of the competition among the dif-
erent compounds for the occupation of the adsorption sites andf displacement effects observed at the exit of the adsorptioned.
Flowers concrete is obtained from the dried hexane extract ofresh flowers. It is formed by essential oil, colouring matter andarge quantities of cuticular waxes. A fractional extraction pro-ess has been proposed in which the flower concrete is meltednd mixed with glass beads, obtaining an inert core (glass)hat supports a given layer of concrete. This process has beensed successfully for the fractionation of several flower con-retes [11,16,18]. Mathematical modelling has been performed197,208]. The volatile oil has been considered to be a mixture
f four compound families (pseudo-components) extracted fromn active layer of concrete on a spherical inert core. Modelling ofxygenated terpenes and oxygenated sesquiterpenes extractionas obtained.
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E. Reverchon, I. De Marco / J. of S
. Liquid feed processing
The fractionation of liquid mixtures in two or more fractionss another relevant process. In a typical apparatus, two pumpseliver the liquid solution and SC-CO2 to the packed column.he packing is an inert material characterized by a large spe-ific surface whose scope is to favour the contact between theiquid and the supercritical fluid. SC-CO2 as a rule flows alonghe column from the bottom to the top, whereas, the liquid solu-ion is usually added to the top. However, it is also possibleo feed the liquid at an intermediate position along the columnnd to add a recycle of part of the fluid phase exiting at theop.
.1. Selection of the operating parameters
The process is based on the different solubilities of the liquidso be separated in SC-CO2. The ideal case is obtained when onlyhe compounds to be extracted are soluble in SC-CO2, whereas,ll the other liquid components are completely insoluble. How-ver, this case is rare and a limited solubility of the other liquidompounds forming the mixture has to be taken into account.or this reason, pressure and temperature of the process have toe accurately chosen to select the conditions at which there ishe maximum difference in solubility among the compounds toe extracted and all the other compounds in the mixture. Alson this case, CO2 density is frequently used as a criterion to findhe conditions of maximum selectivity.
The difference in density between the liquid and SC-CO2 isnother parameter to be taken into account: to allow the counter-urrent operation, SCF density has to be lower than the one ofhe liquid mixture.
The traditional operation of packed columns requires thatiquid flow rate will be larger than the minimum amount thatssures the complete wetting of the packing. The feed ratio is
lso selected to avoid the massive entrainment of the liquid inhe fluid phase (flooding). These conditions have to be respectedlso when a supercritical fluid is used as the fluid-processingedium. The classical calculation in terms of the number of
aocp
able 4ractionation of liquid mixtures by SFE in continuous (C) and semicontinuous (SC)
heoretical equilibrium stages required for separation can alsoe applied.
A possible variation of this processing scheme can consist ofhe adoption of a temperature profile along the column with theim of optimising the separation temperature with respect to theomposition of the mixtures at different levels inside the column.
The extraction of liquid mixtures is controlled by the rela-ive solubilities in SC-CO2 of the various compounds forminghe mixture that is the thermodynamic limitation of the process.
ass transfer between the two phases represents the kinetic limi-ation. The distance from the equilibrium condition is the drivingorce for the separation along the column.
.2. Examples of application
The fractionation of liquid mixtures by SFE has been pro-osed for various applications, as it can be seen in Table 4.
Two examples will be treated in details in the following:exane elimination from vegetable oils that represent a newpproach to seed oils extraction and fried oil fractionation toecover reusable compounds.
.2.1. Hexane elimination from seed oilsThis process represents a different approach to the supercrit-
cal extraction of seed oils. Indeed the supercritical extractionpplied directly to seeds suffers the disadvantage of high costsue to the use of large pressurised vessels and to the intrinsic dis-ontinuous operation. If the approach is to treat the liquid hexaneil mixture after the traditional hexane extraction (composition0% hexane–30% oil), it is possible to use smaller apparatusesnd a continuous operation that allows the processing of largeuantities of the raw mixture.
Hexane and triglycerides are both soluble in SC-CO2, butt a temperature of 40 ◦C, hexane is completely miscible forressures larger than about 100 bar, whereas, at the same temper-
ture, triglycerides show a non-negligible solubility in SC-CO2nly for pressures larger than about 250 bar. Therefore, theseompounds can be separated, operating in a packed tower at lowressures (<200 bar).
plants
Process References
C [209]C [210,211]C [212]C [213]C [214,215]C [216,217]C [218]SC [219]C [220]
rol C [221]C [222]C [223]SC [224]C [225,226]C [222,227]
1 uperc
mpwfoath
3
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58 E. Reverchon, I. De Marco / J. of S
Using these concepts, the fractionation of soybean oil–hexaneixtures has been successfully performed using a 1.8 m tall
acked tower, charged with stainless steel perforated saddlesith a very large specific surface. The extraction has been per-
ormed at 120 bar, 40 ◦C using different starting concentrationf soybean oil in hexane. A single passage in the packed towerllowed to obtain a bottom product formed by soybean oil con-aining down to 20 ppm of hexane residue and to recovery pureexane at the top of the column [220].
.2.2. Fried oil fractionationThe fractionation process using SC-CO2 can be used to purify
sed fried oils. A selective separation of the oil componentsased on their polarity and molecular weight can be attained,ince the degradation compounds are mainly peroxides and poly-ers of the original tryglicerides mixture. The SC-CO2 purifi-
ation of peanut oil used for frying has been studied using theontinuous fractionation in a packed column. The influence ofressure (150–350 bar) and temperature (25–55 ◦C) on the yieldnd on the composition of top and bottom products was stud-ed. Process conditions were selected to separate triglyceridesrom degraded compounds and experimental results indicatedhat the operating conditions leading to maximal triglyceridesecovery in the extract were 350 bar, 55 ◦C, and a solvent-to-eed ratio of 53. Operating at these conditions, it was possibleo recover 97% of the triglycerides feed to the column andpproximately 52 wt.% of the used fried oil. The compositionf the purified top stream was very similar to that of fresh friedil [218].
.3. Mathematical modelling
Mathematical modelling of counter-current packed columnas been studied only by a few authors [228–232] and onlyn some cases with reference to natural matter fractionation228,231].
The most interesting work is the one proposed by Ruivo etl. [228], which performed the dynamic modelling and simula-ion of a packed column. They used the experimental data onmodel binary mixture formed by squalene and methyl oleate,
ractionated using SC-CO2. The model was formed by a set ofartial differential equations that correspond to the differentialass balances on the packed column and algebraic equations
hat describe the mass transfer, the hydrodynamics of the two-hase flow through the packings and the ternary thermodynamicquilibrium for the studied system. The column was consideredt constant temperature. A fair good agreement was obtainedetween measured and predicted composition profiles of theutlet streams over the time.
. Antisolvent extraction
The recovery of solid compounds from a liquid mixture
equires different process approaches since the fixed bed extrac-or is not adapt to process liquid mixtures and the packed towerannot be used in these cases since precipitation of the solidompounds will be obtained on the internal packings.
4
oc
ritical Fluids 38 (2006) 146–166
The supercritical antisolvent extraction (SAE) process is con-eptually very similar to supercritical antisolvent micronizationSAS); but the scope of the process is the recovery of one or moreolid compounds from a liquid mixture. It consists of the contin-ous flow of SC-CO2 and of the liquid mixture in a pressurizedrecipitation vessel. If the process conditions have been prop-rly selected, the liquid is rapidly dissolved in the supercriticaluid, whereas, the solid precipitates at the bottom of the pre-ipitation vessel. Therefore, in a possible representation of therocess two pumps deliver the liquid solution and the supercriti-al fluid, respectively. The precipitation vessel is used to collecthe solid and a vessel located downstream the precipitator andperated at lower pressure (for example, 30 bar and 25 ◦C) issed to recover the liquid.
.1. Selection of the operating parameters
The first step of this process is the formation of a spray of theiquid solution. The scope of this operation is to produce a veryarge liquid surface due to the formation of small liquid dropletso strongly enhance the rate of solubilization of the liquid phasen the supercritical medium. For the same reason, the process iserformed at operating conditions at which the liquid solvent isompletely soluble in SC-CO2. The knowledge of solubility datan the liquid solvents and of the solids in SC-CO2 is mandatoryor this process for the proper selection of process temperaturend pressure.
In the case of SAE, the interactions between thermodynamiconstrains and mass transfer mechanisms also control the pro-ess performance. The enhanced mass transfer that characterizesCFs is again a distinctive advantage of their use as extractionedia, together with the fast and complete separation by sim-
le depressurisation between the supercritical solvent and theiquid.
A limitation of this process is the possible formation of aernary mixture liquid/solid/SC-CO2. Indeed, the presence ofhe liquid can induce an increase of the solubility of the solidompounds in SC-CO2. In this case, the liquid can act as a co-olvent from the point of view of the solid solubilization. Whenhis phenomenon occurs, the part of solid retained in the fluidhase obviously does not precipitate and is lost in the liquidecovered in the separation vessel. The limit case is the completeolubilization of the solid in the fluid phase that produces therocess failure.
.2. Examples of application
Antisolvent extraction until now has been used in a limitedumber of processes (see Table 5) but it has a large potentialor future applications. Some examples will be described in theetails: lecithin extraction from soybean oil, propolis tinctureractionation and tobacco proteins separation.
.2.1. Lecithin extraction from soybean oilCrude lecithin, in general, contains a minimum of 35 wt.%
il, which needs to be reduced to less than 2 wt.% oil before itan be used as an emulsifier. The crude lecithin is convention-
lly refined for removal of oil by repeated solvent extractionsith acetone, as lecithin is ‘acetone insoluble’. Removal of oil
rom crude lecithin by conventional organic solvents has severalisadvantages, such as, a large amount of solvent is needed, its tedious and time-consuming, and a gelatinous lumpy masss formed at the final stage, which reduces the mass transferfficiency of the process.
Some authors have proposed to apply the SAE to this processince seed oils are soluble in SC-CO2 (though at pressures largerhan about 280 bar, as previously specified) and phospholipidsre completely insoluble in this medium. Thus, the proposedrocess consists of operating the antisolvent extraction with SC-O2 at, for example, 400 bar and 40 ◦C with a continuous flowf CO2 and an injection system that sprays in the precipitatorhe lecithin containing oil in form of small droplets [239–241].he oil solubilized in SC-CO2 is extracted and recovered in aeparator operated at low pressure. Lecithin precipitates as aolid powder and is collected time by time when the vessel isischarged.
A further evolution of this process has been proposed byukhopadhyay and Singh [237]. In this method, crude lecithin
s dissolved in hexane and is contacted with dense CO2. The CO2issolution in the solution causes a large partial molar volumeeduction of hexane [242,243]. As a result, there is a reduction ofts solvent power for lecithin, producing a selective precipitationf lecithin.
.2.2. Propolis tincture fractionationPropolis contains a high concentration of flavonoids, which
re used in a wide range of cosmetic and health food preparationsor their antimicrobial properties. Propolis is usually dissolved inthanol or ethanol/water mixtures to remove insoluble materialuch as waxes. The resultant solution is a propolis tincture.
A supercritical antisolvent extraction process has been pro-osed for the fractionation of propolis tincture [233] to obtainavonoids and essential oil fractions by extraction, and toemove high molecular mass components by antisolvent pre-ipitation. Flavonoids are practically insoluble in pure CO2, butufficiently soluble in CO2 + ethanol to enable their separationrom high molecular mass and/or more polar components. Inhe first step of the process, supercritical CO2 is used both as an
ntisolvent to precipitate high molecular weight components,nd as a solvent to extract the ethanol and soluble componentsf the propolis. This extract is then fractionated in two sepa-ation steps to create a concentrated flavonoid fraction as the
5
(
ritical Fluids 38 (2006) 146–166 159
rimary product, and an essential oil/ethanol fraction as a sec-ndary product. Operating at 300 bar, almost 100% recovery ofavonoids was obtained. The optimum tincture concentrationppeared to be about 10 mass%. The concentration of propolisn the tincture is the parameter that has the greatest effect on theield and concentration of flavonoids in the product fraction.he process has been successfully scaled up to a demonstra-
ion scale using optimized pressure, temperature, flow ratio andincture concentrations obtained from laboratory and pilot scalerials.
.2.3. Proteins extraction from tobaccoCigarette manufacturers have devised systems to reduce the
icotine and tar content of the burning tobacco for health reasons.ost of these systems have resulted in a safer smoking product,
ut they do not remove all of the undesirable constituents in theobacco smoke. Proteins in cured tobacco are either precursorsf undesired compounds in the smoke either a valuable sourcef useful compounds. Therefore, the supercritical antisolventxtraction has been used by Scrugli et al. [238] to remove pro-ein compounds from cured tobacco by ethanolic extraction ando recover the proteic compounds from the obtained solution.lkaloids like nicotine are soluble in SC-CO2 especially at highensities, cuticular waxes and flavouring compounds can alsoeen readily extracted. Therefore, a fractionation of the ethanolicxtract is possible, if processing conditions are selected to induceroteic compounds precipitation and the transfer in the fluidhase of the liquid solvent together with nicotine, waxes andavouring components. The experiments have been performedt different pressures and solid concentrations. The ethanolicxtract was efficiently fractionated in all the experiments. Thehemical analyzes performed on the fractions recovered shownhat the yield of precipitated material was about 40% (w/w ofxtract) in each experiment. Particularly interesting is the totalbsence of nicotine in the precipitates, whereas, it is totallyecovered with flavours and pigments, in the ethanolic residues.
.3. Mathematical modelling
No specific papers dedicated to SAE modelling have untilow been published. However, due to the similarities of thisrocess with SAS, part of the considerations developed for thatrocess [244–248] could be adapted to SAE.
Since only precipitation is required in SAE with no speci-cations on particle size, the spray formation/efficiency is notarticularly relevant even if a large contact surface favours theate of precipitation.
Phase equilibria will play a role even more relevant than inAS. Indeed, in SAE we are interested in the separation of theolid phase and, as a rule, complex mixtures are processed; there-ore, interactions among the compounds present in the mixturere involved and will be very difficult to be predicted.
. Conclusions and perspectives
SFE and liquids fractionation in the period of time considered1996 to present time) have moved along two major direc-
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60 E. Reverchon, I. De Marco / J. of S
ions: consolidation of the knowledge in previously exploredelds (e.g., essential oils, vegetable oils, etc.) and explorationf several high added values compound categories of interestor nutraceutical, cosmetic and pharmaceutical industries. Thisecond approach is scientifically challenging but also necessaryo find applications that are industrially competitive with the tra-itional processes based on cheaper technologies and plants. Inome cases, the extraction problems proved to be very complexnd as a consequence more evolved process schemes (multistepxtraction, continuous solid processing, multistage separations,o-solvents) have been adopted to overcome these problems.owever, a large quantity of work is still required, particularly,
n the liquid fractionation process that has been used only in aimited quantity of applications, but, has a large potential. Super-ritical antisolvent extraction represents a case apart since it hasarge possibilities of application; but it has been explored onlyn a very few cases.
Mathematical modelling has also been proposed in someases, but this activity is far to be complete, considered the largeuantity of possible structures, interactions, etc.
The development of industrial applications of SFE processess in progress, especially in the field of nutraceuticals productshat are followed with attention by various companies. Liquidractionation and supercritical antisolvent extraction have untilow tested only up to the pilot scale.
eferences
[1] R.M. Smith, Supercritical fluids in separation science—the dreams, thereality and the future, J. Chromatogr. A 856 (1999) 83–115.
[2] E. Reverchon, Supercritical fluid extraction and fractionation of essentialoils and related products, J. Supercrit. Fluids 10 (1997) 1–37.
[3] M.A.A. Meireles, Supercritical extraction from solid: process designdata (2001–2003), Current Opin. Solid State Mater. Sci. 7 (2003) 321–330.
[4] Q. Lang, C.M. Wai, Supercritical fluid extraction in herbal and nat-ural product studies—a practical review, Talanta 53 (2001) 771–782.
[5] C. Turner, C.S. Eskilsson, E. Bjorklund, Review: collection in analytical-scale supercritical fluid extraction, J. Chromatogr. A 947 (2002)1–22.
[6] G. Brunner, Supercritical fluids: technology and application to food pro-cessing, J. Food Eng. 67 (2005) 21–33.
[7] E. Stahl, K.W. Quirin, D. Gerard, Verdichtete Gase zur Extraction undRaffination, Springer, Berlin, 1997.
[8] D.A. Moyler, in: M.B. King, T.R. Bott (Eds.), Extraction of Flavours andFragrances with Compressed CO2, Extraction of Natural Products UsingNear-critical Solvents, Blackie, Glasgow, 1993.
[9] K. Kerrola, Literature review: isolation of essential oils and flavour com-pounds by dense carbon dioxide, Food Rev. Int. 11 (1995) 547–573.
[10] P.T.V. Rosa, M.A.A. Meireles, Supercritical technology in Brazil: systeminvestigated, J. Supercrit. Fluids 34 (2005) 109–117.
[11] E. Reverchon, G. Della Porta, D. Gorgoglione, Supercritical CO2 frac-tionation of jasmine concrete, J. Supercrit. Fluids 8 (1995) 60–65.
[12] E. Reverchon, G. Della Porta, F. Senatore, Supercritical CO2 extractionand fractionation of lavender essential oil and waxes, J. Agric. Food Chem.43 (1995) 1654–1658.
[13] E. Reverchon, Fractional separation of SCF extracts from marjoramleaves: mass transfer and optimization, J. Supercrit. Fluids 5 (1992)256–261.
[14] E. Reverchon, A. Ambruosi, F. Senatore, Isolation of peppermint oil usingsupercritical CO2 extraction, J. Flavour Fragr. 9 (1994) 19–23.
ritical Fluids 38 (2006) 146–166
[15] E. Reverchon, G. Della Porta, R. Taddeo, Extraction of sage essential oilby supercritical CO2: influence of some process parameters, J. Supercrit.Fluids 8 (1995) 302–309.
[16] E. Reverchon, G. Della Porta, Rose concrete fractionation by supercriticalCO2, J. Supercrit. Fluids 9 (1996) 199–204.
[17] G. Della Porta, S. Porcedda, B. Marongiu, E. Reverchon, Isolation ofeucalyptus oil by supercritical fluid extraction, Flavour Fragr. J. 14 (1999)214–218.
[18] E. Reverchon, G. Della Porta, Tuberose concrete fractionation by super-critical carbon dioxide, J. Agric. Food Chem. 45 (1997) 1356–1360.
[19] G. Della Porta, R. Taddeo, E. D’Urso, E. Reverchon, Isolation of clovebud and star anise essential oil by supercritical CO2 extraction, Lebensm.-Wiss. U.-Technol. 31 (1998) 454–460.
[20] A. Caredda, B. Marongiu, S. Porcedda, C. Soro, Supercritical carbondioxide extraction and characterization of Laurus nobilis essential oil, J.Agric. Food Chem. 50 (2002) 1492–1496.
[21] B. Marongiu, S. Porcedda, G. Della Porta, E. Reverchon, Extractionand isolation of Salvia desoleana and Mentha spicata subsp. insularisessential oils by supercritical CO2, Flavour Fragr. J. 16 (2001) 384–388.
[22] B. Marongiu, S. Porcedda, A. Piras, A. Rosa, M. Deiana, M.A. Dessı,Antioxidant activity of supercritical extract of Melissa officinalis subsp.officinalis and Melissa officinalis subsp. inodora, Phytother. Res. 18(2004) 789–792.
[23] B. Simandi, A. Deak, E. Ronyai, G. Yanxiang, T. Veress, E. Lemberkovics,M. Then, A. Sass-Kiss, Z. Vamos-Falusi, Supercritical carbon dioxideextraction and fractionation of fennel oil, J. Agric. Food Chem. 47 (1999)1635–1640.
[24] B. Simandi, A. Sass-Kiss, B. Czukor, A. Deak, A. Prechl, A. Csordas,J. Sawinsky, Pilot-scale extraction and fractional separation of onionoleoresin using supercritical carbon dioxide, J. Food Engrg. 46 (2000)183–188.
[25] E. Vagi, B. Simandi, H.G. Daood, A. Deak, J. Sawinsky, Recovery ofpigments from Origanum majorana L. by extraction with supercriticalcarbon dioxide, J. Agric. Food Chem. 50 (2002) 2297–2301.
[26] M.M. Esquivel, M.A. Ribeiro, M.G. Bernardo-Gil, Supercritical extrac-tion of savory oil: study of antioxidant activity and extract characteriza-tion, J. Supercrit. Fluids 14 (1999) 129–138.
[27] M.A. Ribeiro, M.G. Bernardo-Gil, M.M. Esquivel, Melissa officinalis L.:study of antioxidant activity in supercritical residues, J. Supercrit. Fluids21 (2001) 51–60.
[28] E. Dauksas, P.R. Venskutonis, B. Sivik, T. Nillson, Effect of fast CO2
pressure changes on the yield of lovage (Levisticum officinale Koch.)and celery (Apium graveolens L.) extracts, J. Supercrit. Fluids 22 (2002)20–2101.
[29] E. Dauksas, P.R. Venskutonis, V. Povilaityte, B. Sivik, Rapid screen-ing of antioxidant activity of sage (Salvia officinalis L.) extractsobtained by supercritical carbon dioxide at different extraction condi-tions, Nahrung/Food 45 (2001) 338–341.
[30] B.-J. Wang, Y.-H. Lien, Z.-R. Yu, Supercritical fluid extractivefractionation—study of the antioxidant activities of propolis, Food Chem.86 (2004) 237–243.
[31] B.-J. Wang, C.-T. Liu, C.-Y. Tseng, C.-P. Wu, Z.-R. Yu, Hepatoprotectiveand antioxidant effects of Bupleurum kaoi Liu (Chao et Chuang) extractand its fractions fractionated using supercritical CO2 on CCl4-inducedliver damage, Food Chem. Toxicol. 42 (2004) 609–617.
[32] G. Vasapollo, L. Longo, L. Restio, L. Ciurlia, Innovative supercriticalCO2 extraction of Lycopene from tomato in the presence of vegetable oilas co-solvent, J. Supercrit. Fluids 29 (2004) 87–96.
[33] H.K. Kiriamiti, S. Camy, C. Gourdon, J.-S. Condoret, Supercritical carbondioxide processing of pyrethrum oleoresin and pale, J. Agric. Food Chem.51 (2003) 880–884.
[34] H.K. Kiriamiti, S. Camy, C. Gourdon, J.-S. Condoret, Pyrethrin extraction
from pyrethrum flowers using carbon dioxide, J. Supercrit. Fluids 26(2003) 193–200.
[35] F. Gaspar, T. Lu, R. Santos, B. Al-Duri, Modelling the extraction of essen-tial oils with compressed carbon dioxide, J. Supercrit. Fluids 25 (2003)247–260.
uperc
E. Reverchon, I. De Marco / J. of S
[36] R.L. Smith Jr., R.M. Malaluan, W.B. Setianto, H. Inomata, K. Arai,Separation of cashew (Anacardium occidentale L.) nut shell liquid withsupercritical carbon dioxide, Biores. Technol. 88 (2003) 1–7.
[37] E. Ibanez, A. Oca, G. De Murga, S. Lopez-Sebastian, J. Tabera, G.Reglero, Supercritical fluid extraction and fractionation of different pre-processed rosemary plants, J. Agric. Food Chem. 47 (1999) 1400–1404.
[38] F.J. Senorans, E. Ibanez, S. Cavero, J. Tabera, G. Reglero, Liq-uid chromatographic-mass spectrometric analysis of supercritical fluidextracts of rosemary plants, J. Chromatogr. A 870 (2000) 491–499.
[39] P. Ramirez, F.J. Senorans, E. Ibanez, G. Reglero, Separation of rose-mary antioxidant compounds by supercritical fluid chromatography oncoated packed capillary columns, J. Chromatogr. A 1057 (2004) 241–245.
[40] D. Grigonis, P.R. Venskutonis, B. Sivik, M. Sandahl, C.S. Eskilsson, Com-parison of different extraction techniques for isolation of antioxidantsfrom sweet grass (Hierochloe odorata), J. Supercrit. Fluids 33 (2005)223–233.
[41] E. Dauksas, P.R. Venskutonis, B. Sivik, Supercritical fluid extraction ofborage (Borago officinalis L.) seeds with pure CO2 and its mixture withcaprylic acid methyl ester, J. Supercrit. Fluids 22 (2002) 211–219.
[42] C. Bicchi, A. Binello, P. Rubiolo, Determination of phenolic diter-pene antioxidants in rosemary (Rosmarinus officinalis L.) with differentmethods of extraction and analysis, Phytochem. Anal. 11 (2000) 236–242.
[43] F. Le Floch, M.T. Tena, A. Rios, M. Valcarcel, Supercritical fluidextraction of phenol compounds from olive leaves, Talanta 46 (1998)1123–1130.
[44] J.M. del Valle, T. Rogalinski, C. Zentl, G. Brunner, Extraction of boldo(Peumus boldus M.) leaves with supercritical CO2 and hot pressurizedwater, Food Res. Intern. 38 (2005) 203–213.
[45] A.H. El-Ghorab, K.F. El-Massry, F. Marx, H.M. Fadel, Antioxidant activ-ity of Egyptian Eucaliptus camaldulensis var. brevirostris leaf extracts,Nahrung/Food 47 (2003) 41–45.
[46] K.C. Zancan, M.O.M. Marques, A.J. Petenate, M.A.M. Meireles, Extrac-tion of ginger (Zingiber officinale Roscoe) oleoresin with CO2 and co-solvents: a study of the antioxidant action of the extracts, J. Supercrit.Fluids 24 (2002) 57–76.
[47] P.F. Leal, M.E.M. Braga, D.N. Sato, J.E. Carvalho, M.O.M. Marques,M.A.M. Meireles, Functional properties of spice extracts obtained viasupercritical fluid extraction, J. Agric. Food Chem. 51 (2003) 2520–2525.
[48] M.E.M. Braga, P.F. Leal, J.E. Carvalho, M.A.A. Meireles, Comparison ofyield, composition, and antioxidant activity of turmeric (Curcuma longaL.) extracts using various techniques, J. Agric. Food Chem. 51 (2003)6604–6611.
[49] S.K. Yoda, M.O.M. Marques, A.J. Petenate, M.A.A. Meireles, Super-critical fluid extraction from Stevia rebaudiana Bertoni using CO2 andCO2 + water: extraction kinetics and identification of extracted compo-nents, J. Food Engrg. 57 (2003) 125–134.
[50] M.A. Rostagno, J.M.A. Araujo, D. Sandi, Supercritical fluid extrac-tion of isoflavones from soybean flour, Food Chem. 78 (2002) 111–117.
[51] Q. Hu, Y. Hu, J. Xu, Free radical-scavenging activity of Aloe vera (Aloebarbadensis Miller) extracts by supercritical carbon dioxide extraction,Food Chem. 91 (2005) 85–90.
[52] A.T. Quitain, S. Katoh, T. Moriyoshi, Isolation of antimicrobials andantioxidants from moso-bamboo (Phyllostachys Heterocycla) by super-critical CO2 extraction and subsequent hydrothermal treatment of theresidues, Ind. Eng. Chem. Res. 43 (2004) 1056–1060.
[53] M.D.A. Saldana, C. Zentl, R. Mohamed, G. Brunner, Extraction ofmethylxanthines from guarana seeds, mate leaves, and cocoa beans usingsupercritical carbon dioxide and ethanol, J. Agric. Food Chem. 50 (2002)
4820–4826.
[54] M. Hamburger, D. Baumann, S. Adler, Supercritical carbon dioxideextraction of selected medicinal plants—effects of high pressure andadded ethanol on yield of extracted substances, Phytochem. Anal. 15(2004) 46–54.
ritical Fluids 38 (2006) 146–166 161
[55] J. Klimes, J. Sochor, J. Kriz, A study of the conditions of the supercriticalfluid extraction in the analysis of selected anti-inflammatory drugs inplasma, Il Farmaco 57 (2002) 117–122.
[56] N. Aghel, Y. Yamini, A. Hadjiakhoondi, S.M. Pourmortazavi, Supercriti-cal carbon dioxide extraction of Mentha pulegium L. essential oil, Talanta62 (2004) 407–411.
[57] Y. Cui, C.Y.W. Ang, Supercritical fluid extraction and high-performanceliquid chromatographic determination of phloroglucinols in St. John’sWort (Hypericum perforatum L.), J. Agric. Food Chem. 50 (2002)2755–2759.
[58] X.-L. Cao, Y. Tian, T.-Y. Zhang, Y. Ito, Supercritical fluid extraction ofcatechins from Cratoxylum prumifolium Dyer and subsequent purificationby high-speed counter-current chromatography, J. Chromatogr. A 898(2000) 75–81.
[59] X. Cao, Y. Ito, Supercritical fluid extraction of grape seed oil and subse-quent separation of free fatty acids by high-speed counter-current chro-matography, J. Chromatogr. A 1021 (2003) 117–124.
[60] C. Yang, Y.-R. Xu, W.-X. Yao, Extraction of pharmaceutical componentsfrom Ginkgo biloba leaves using supercritical carbon dioxide, J. Agric.Food Chem. 50 (2002) 846–849.
[61] X.-S. Shu, Z.-H. Gao, X.-L. Yang, Supercritical fluid extraction ofsapogenins from tubers of Smilax china, Fitoterapia 75 (2004) 656–661.
[62] O.J. Catchpole, N.B. Perry, B.M.T. da Silva, J.B. Grey, B.M. Small-field, Supercritical extraction of herbs I: Saw Palmetto, St. John’sWort, Kava Root, and Echinacea, J. Supercrit. Fluids 22 (2002) 129–138.
[63] H. Sovova, M. Sajfrtova, M. Bartlova, L. Opletal, Near-critical extractionof pigments and oleoresin from stinging nettle leaves, J. Supercrit. Fluids30 (2004) 213–224.
[64] G.-B. Lim, S.-Y. Lee, E.-K. Lee, S.-J. Haam, W.-S. Kim, Separation ofAstaxanthin from red yeast Phaffia rhodozyma by supercritical carbondioxide extraction, Biochem. Eng. J. 11 (2002) 181–187.
[65] C. Quan, S. Li, S. Tian, H. Xu, A. Lin, L. Gu, Supercritical fluid extractionand clean-up of organochlorine pesticides in ginseng, J. Supercrit. Fluids31 (2004) 149–157.
[66] Y.-C. Ling, H.-C. Teng, C. Cartwright, Supercritical fluid extraction andclean-up of organochlorine pesticides in Chinese herbal medicine, J.Chromatogr. A 835 (1999) 145–157.
[67] G. Leeke, F. Gaspar, R. Santos, Influence of water on the extraction ofessential oils from a model herb using supercritical carbon dioxide, Ind.Eng. Chem. Res. 41 (2002) 2033–2039.
[68] V. Illes, O. Szalai, M. Then, H.G. Daood, S. Perneczki, Extraction ofhiprose fruit by supercritical CO2 and propane, J. Supercrit. Fluids 10(1997) 209–218.
[69] A. Menaker, M. Kravets, M. Koel, A. Orav, Identification and character-ization of supercritical fluid extracts from herbs, C. R. Chimie 7 (2004)629–633.
[70] K.-L. Chiu, Y.-C. Cheng, J.-H. Chen, C.J. Chang, P.-W. Yang, Supercrit-ical fluids extraction of Ginkgo ginkgolides and flavonoids, J. Supercrit.Fluids 24 (2002) 77–87.
[71] J.W. King, A. Mohamed, S.L. Taylor, T. Mebrahtu, C. Paul, Supercriticalfluid extraction of Vernonia galamensis seeds, Ind. Crops Products 14(2001) 241–249.
[72] I.S. Sanal, E. Bayraktar, U. Mehmetoglu, A. Calimli, Determinationof optimum conditions for SC-(CO2 + ethanol) extraction of �-carotenefrom apricot pomace using response surface methodology, J. Supercrit.Fluids 34 (2005) 331–338.
[73] J. da Cruz Francisco, B. Danielsson, A. Kozubek, E. Szwajcer Dey,Application of supercritical carbon dioxide for the extraction ofalkylresorcinols from rye bran, J. Supercrit. Fluids 35 (2005) 220–226.
[74] L. Teberikler, S.S. Koseoglu, A. Akgerman, Deoling of crude lecithin
using supercritical carbon dioxide in the presence of co-solvents, J. FoodSci. 66 (2001) 850–853.
[75] L. Teberikler, S.S. Koseoglu, A. Akgerman, Selective extraction of phos-phatilylcholine from lecithin by supercritical carbon dioxide/ethanol mix-ture, J. Am. Oil Chem. Soc. (JAOCS) 78 (2001) 115–119.
1 uperc
62 E. Reverchon, I. De Marco / J. of S
[76] R. Eggers, S.K. Voges, Ph.T. Jaeger, Solid bed properties in supercriticalprocessing, in: I. Kikic, M. Perrut (Eds.), Proceedings of the 9th Meetingon Supercritical Fluids, Trieste (Italy), 2004, E11.pdf.
[77] http://webbook.nist.gov/chemistry/fluid.[78] R. Span, W. Wagner, A new equation of state for carbon dioxide covering
the fluid region from the triple-point temperature to 1100 K at pressuresup to 800 MPa, J. Phys. Chem. Ref. Data 25 (1996) 1509–1596.
[79] K.H. Kim, J. Hong, Equilibrium solubilities of spearmint oil componentsin supercritical carbon dioxide, Fluid Phase Equil. 164 (1999) 107–115.
[80] Y. Iwai, T. Morotomi, K. Sakamoto, Y. Koga, Y. Arai, High-pressurevapor–liquid equilibria for carbon dioxide + Limonene, J. Chem. Eng.Data 41 (1996) 951–952.
[81] Ph. Marteau, J. Obriot, R. Tufeu, Experimental determination ofvapor–liquid equilibria of CO2 + Limonene and CO2 + citral mixtures,J. Supercrit. Fluids 8 (1995) 20–24.
[82] M. Akgun, N.A. Akgun, S. Dincer, Phase behaviour of essential oil com-ponents in supercritical carbon dioxide, J. Supercrit. Fluids 15 (1999)117–125.
[83] S. Raeissi, C.J. Peters, Bubble-point pressures of the binary system carbondioxide + linalool, J. Supercrit. Fluids 20 (2001) 221–228.
[84] E. Reverchon, P. Russo, A. Stassi, Solubilities of solid octacosane andtriacontane in supercritical carbon dioxide, J. Chem. Eng. Data 38 (1993)458–460.
[85] A. Molero, E. Gomez, Martinez de la Ossa, Quality of borage seed oilextracted by liquid and supercritical carbon dioxide, Chem. Eng. J. 88(2002) 103–109.
[86] I. Papamichail, V. Louli, K. Magoulas, Supercritical fluid extraction ofcelery seed oil, J. Supercrit. Fluids 18 (2000) 213–226.
[87] V. Illes, H.G. Daood, S. Perneczki, L. Szokonya, M. Then, Extraction ofcoriander seed oil by CO2 and propane at super- and subcritical condi-tions, J. Supercrit. Fluids 17 (2000) 177–186.
[88] K. Szentmihalyi, P. Vinkler, B. Lakatos, V. Illes, M. Then, Rose hip (Rosacanina L.) oil obtained from waste hip seeds by different extraction meth-ods, Biores. Technol. 82 (2002) 195–201.
[89] J.M. del Valle, O. Rivera, M. Mattea, L. Ruetsch, J. Baghero, A. Flores,Supercritical CO2 processing of pretreated rosehip seeds: effect of pro-cess scale on oil extraction kinetics, J. Supercrit. Fluids 31 (2004) 159–174.
[90] E. Reverchon, L. Sesti Osseo, Comparison of processes for the supercrit-ical CO2 extraction of oil from soybean seeds, J. Am. Oil Chem. Soc.(JAOCS) 71 (9) (1994) 1007–1012.
[91] V.M. Rodrigues, P.T.V. Tosa, M.O.M. Marques, A.J. Petenate, M.A.A.Meireles, Supercritical extraction of essential oil from Aniseed(Pimpinella anisum L.) using CO2: solubility, kinetics and compositiondata, J. Agric. Food Chem. 51 (2003) 1518–1523.
[92] A.R. Monteiro, M.A. Meireles, M.O.M. Marques, A.J. Petenate, Extrac-tion of the soluble material from the shells of the bacuri fruit (Platoniainsignis Mart) with pressurized CO2 and other solvents, J. Supercrit. Flu-ids 11 (1997) 91–102.
[93] M.C. Dyaz-Maroto, M.S. Perez-Coello, M.D. Cabezudo, Supercriticalcarbon dioxide extraction of volatiles from spices. Comparison withsimultaneous distillation–extraction, J. Chromatogr. A 947 (2002) 23–29.
[94] R.N. Patel, S. Bandyopadhyay, A. Ganesh, Extraction of cashew (Anac-ardium occidentale) nut shell liquid using supercritical carbon dioxide,Biores. Technol. 97 (2006) 847–853.
[95] N.P. Povh, M.O.M. Marques, M.A.A. Meireles, Supercritical CO2 extrac-tion of essential oil and oleoresin from chamomile (Chamomilla recutita[L.] Rauschert), J. Supercrit. Fluids 21 (2001) 245–256.
[96] B. Barjaktarovic, M. Sovilj, Z. Knez, Chemical composition of Junipe-rus communis L. fruits supercritical CO2 extracts: dependence on pres-sure and extraction time, J. Agric. Food Chem. 53 (2005) 2630–2636.
extraction of essential oil components from lemon-scented botanicals,Lebensm.-Wiss. U.-Technol. 35 (2002) 319–324.
[98] L.H.C. Carlson, R.A.F. Machado, C.B. Spricigo, L.K. Pereira, A. Bolzan,Extraction of lemongrass essential oil with dense carbon dioxide, J. Super-crit. Fluids 21 (2001) 33–39.
ritical Fluids 38 (2006) 146–166
[99] E. Dauksas, P.R. Venskutonis, Extraction of Lovage (Levisticum officinaleKoch.) roots by carbon dioxide. 1. Effect of CO2 parameters on the yieldof the extract, J. Agric. Food Chem. 46 (1998) 4347–4351.
[100] E. Dauksas, P.R. Venskutonis, B. Sivik, Supercritical CO2 extraction ofthe main constituents of lovage (Levisticum officinale Koch.) essential oilin model systems and over-ground botanical parts of the plant, J. Supercrit.Fluids 15 (1999) 51–62.
[101] M.R.A. Rodrigues, E.B. Caramao, J.G. Dos Santos, C. Dariva, J.V.Oliveira, The effects of temperature and pressure on the characteristicsof the extracts from high-pressure CO2 extraction of Majorana hortensisMoench, J. Agric. Food Chem. 51 (2003) 453–456.
[102] B. Simandi, M. Oszagyan, E. Lemberkovics, A. Kery, J. Kaszacs, F.Thyrion, T. Matyas, Supercritical carbon dioxide extraction and fraction-ation of oregano oleoresin, Food Res. Intern. 31 (1998) 723–728.
[103] M.R.A. Rodrigues, L.C. Krause, E.B. Caramao, J.G. Dos Santos, C.Dariva, J.V. De Oliveira, Chemical composition and extraction yield ofthe extract of Origanum vulgare obtained from sub- and supercriticalCO2, J. Agric. Food Chem. 52 (2004) 3042–3047.
[104] M.N. Hassan, N.N.Ab. Rahman, M.H. Ibrahim, A.K. Mohd Omar, Simplefractionation through the supercritical carbon dioxide extraction of palmkernel oil, Separ. Purif. Technol. 19 (2000) 113–120.
[105] N.A. Nik Norulaini, I.S. Md Zaidul, O. Anuar, A.K. Mohd Omar, Super-critical enhancement for separation of lauric acid and oleic acid in palmkernel oil (PKO), Separ. Purif. Technol. 39 (2004) 133–138.
[106] N.A. Nik Norulaini, I.S. Md Zaidul, O. Anuar, A.K. Mohd Omar, Super-critical enhancement for separation of lauric acid and oleic acid in palmkernel oil (PKO), Separ. Purif. Technol. 35 (2004) 55–60.
[107] S.R.S. Ferreira, Z.L. Nikolov, L.K. Doraiswamy, M.A.M. Meireles, A.J.Petenate, Supercritical fluid extraction of black pepper (Piper nigrun L.)essential oil, J. Supercrit. Fluids 14 (1999) 235–245.
[108] N. Tipsrisukond, L.N. Fernando, A.D. Clarke, Antioxidant effects ofessential oil and oleoresin of black pepper from supercritical carbondioxide extractions in ground pork, J. Agric. Food Chem. 46 (1998)4329–4333.
[109] C. Duarte, M. Moldao-Martins, A.F. Gouveia, S. Beirao da Costa, A.E.Leitao, M.G. Bernardo-Gil, Supercritical fluid extraction of red pepper(Capsicum frutescens L.), J. Supercrit. Fluids 30 (2004) 155–161.
[110] S. Sonsuzer, S. Sahin, L. Yilmaz, Optimization of supercritical CO2
extraction of Thymbra spicata oil, J. Supercrit. Fluids 30 (2004) 189–199.[111] M. Moldao-Martins, A. Palavra, M.L. Beirao da Costa, M.G. Bernardo-
Gil, Supercritical CO2 extraction of Thymus zygis L. subsp. sylvestrisaroma, J. Supercrit. Fluids 18 (2000) 25–34.
[112] V.G. Zuin, J.H. Yariwake, C. Bicchi, Fast supercritical fluid extractionand high-resolution gas chromatography with electron-capture and flamephotometric detection for multiresidue screening of organochlorine andorganophosphorus pesticides in Brazil’s medicinal plants, J. Chromatogr.A 985 (2003) 159–166.
[113] M. Danaher, M. O’Keeffe, J.D. Glennon, Development and optimisationof a method for the extraction of benzimidazoles from animal liver usingsupercritical carbon dioxide, Analyt. Chim. Acta 483 (2003) 313–324.
[114] M.E.M. Braga, P.A.D. Ehlert, L.C. Ming, M.A.M. Meireles, Super-critical fluid extraction from Lippia alba: global yields, kinetic data,and extract chemical composition, J. Supercrit. Fluids 34 (2005) 149–156.
[115] E.E. Stashenko, B.E. Jaramillo, J.R. Martinez, Comparison of differentextraction methods for the analysis of volatile secondary metabolitesof Lippia alba (Mill.) N.E. Brown, grown in Colombia, and evaluationof its in vitro antioxidant activity, J. Chromatogr. A 1025 (2004) 93–103.
[116] G. Della Porta, E. Reverchon, A. Benakis, Extraction and fractionationof antimalaric drugs by supercritical fluid, in: I. Kikic, M. Perrut (Eds.),Proceedings of the 9th Meeting On Supercritical Fluids, Trieste, Italy,2004, N26.pdf.
[117] J.M. del Valle, C. Godoy, M. Asencio, J.M. Aguilera, Recovery of antiox-idants from boldo (Peamus boldus M.) by conventional and supercriticalCO2 extraction, Food Res. Intern. 37 (2004) 695–702.
[118] L.F. de Franca, G. Reber, M.A.M. Meireles, N.T. Machado, G. Brunner,Supercritical extraction of carotenoids and lipids from buriti (Mauritia
uperc
E. Reverchon, I. De Marco / J. of S
flexuosa), a fruit from the Amazon region, J. Supercrit. Fluids 14 (1999)247–256.
[119] V. Sewram, M.W. Raynor, D.A. Mulholland, D.M. Raidoo, The uterotonicactivity of compounds isolated from the supercritical extract of Ekebergiacapensis, J. Pharm. Biomed. Anal. 24 (2000) 133–145.
[120] R.S. Mohamed, M.D.A. Saldana, P. Mazzafera, C. Zetzl, G. Brunner,Extraction of Caffeine, Theobromine, and cocoa butter from braziliancocoa beans using supercritical CO2 and ethane, Ind. Eng. Chem. Res.41 (2002) 6751–6758.
[121] M.D.A. Saldana, R.S. Mohamed, P. Mazzafera, Extraction of cocoa butterfrom Brazilian cocoa beans using supercritical CO2 and ethane, FluidPhase Equil. 194–197 (2002) 885–894.
[122] E. Ramos, E. Valero, E. Ibanez, G. Reglero, J. Tabera, Obtention of abrewed coffee aroma extract by an optimized supercritical CO2-basedprocess, J. Agric. Food Chem. 46 (1998) 4011–4016.
[123] L. Sun, K.A. Rezael, F. Temelli, B. Ooraikul, Supercritical fluid extractionof alkylamides from Echinacea angustifolia, J. Agric. Food Chem. 50(2002) 3947–3953.
[124] B. Yepez, M. Espinosa, S. Lopez, G. Bolanos, Producing antioxidantfractions from herbaceous matrices by supercritical fluid extraction, FluidPhase Equil. 194–197 (2002) 879–884.
[125] M. Lopez, L. Arce, J. Garrido, A. Rios, M. Valcarcel, Selective extractionof Astaxanthin from crustaceans by use of supercritical carbon dioxide,Talanta 64 (2004) 726–731.
[126] B. Simandi, S.T. Kristo, A. Kery, L.K. Selmeczi, I. Kmecz, S. Kemeny,Supercritical fluid extraction of dandelion leaves, J. Supercrit. Fluids 23(2002) 135–142.
[127] D.J.M. Gomez-Coronado, E. Ibanez, F.J. Ruperez, C. Barbas, Tocopherolmeasurement in edible products of vegetable origin, J. Chromatogr. A1054 (2004) 227–233.
[128] A.J. Mossi, R.L. Cansian, A.Z. Carvalho, C. Dariva, J.V. Oliveira, M.Mazutti, I.N. Filho, S. Echeverrigaray, Extraction and characterizationof volatile compounds in Maytenus ilicifolia, using high-pressure CO2,Fitoterapia 75 (2004) 168–178.
[129] L. Cretnik, M. Skerget, Z. Knez, Separation of parthenolide from fever-few: performance of conventional and high-pressure extraction tech-niques, Separ. Purif. Technol. 41 (2005) 13–20.
[130] M.D.A. Saldana, C. Zetzl, R.S. Mohamed, G. Brunner, Decaffeination ofguarana seeds in a microextraction column using water-saturated CO2, J.Supercrit. Fluids 22 (2002) 119–127.
[131] E.M.Z. Michielin, L.F.V. Bresciani, L. Danielski, R.A. Yunes, S.R.S. Fer-riera, Composition profile of horsetail (Equisetum giganteum L.) oleores:comparing SFE and organic solvents extraction, J. Supercrit. Fluids 33(2005) 131–138.
[132] J.-L. Mau, P.-T. Ko, C.-C. Chyau, Aroma characterization and antioxidantactivity of supercritical carbon dioxide extracts from Terminalia catappaleaves, Food Res. Intern. 36 (2003) 97–104.
[133] T.-F. Ko, Y.-M. Weng, R.Y.-Y. Chiou, Squalene content and antioxidantactivity of Terminalia catappa leaves and seeds, J. Agric. Food Chem. 50(2002) 5343–5348.
[134] E. Vagi, E. Rapavi, M. Hadolin, K. Vasarhelyine Peredi, A. Balazs, A.Blazovics, B. Simandi, Phenolic and triterpenoid antioxidants from Ori-ganum majorana L. herb and extracts obtained with different solvents, J.Agric. Food Chem. 53 (2005) 17–21.
[135] A.H. El-Ghoran, A.F. Mansour, K.F. El-massry, Effect of extraction meth-ods on the chemical composition and antioxidant activity of Egyptianmarjoram (Majorana hortensis Moench), Flavour Fragr. J. 19 (2004)54–61.
[136] A.A. Esmelindro, J. Dos Santos Girardi, A. Mossi, R. Assis Jacques,C. Dariva, Influence of agronomic variables on the composition of matetea leaves (Ilex paraguariensis) extracts obtained from CO2 extraction at30 ◦C and 175 bar, J. Agric. Food Chem. 52 (2004) 1990–1995.
[137] E. Ziemons, E. Goffin, R. Lejeune, A. Proenca de Cunha, L. Angenot,
L. Thunus, Supercritical carbon dioxide extraction of tagitinin C fromTithonia diversifolia, J. Supercrit. Fluids 33 (2005) 53–59.
[138] R.L. Mendes, B.P. Nobre, M.T. Cardoso, A.P. Pereira, A.F. Palavra, Super-critical carbon dioxide extraction of compounds with pharmaceuticalimportance from microalgae, Inorg. Chim. Acta 356 (2003) 328–334.
ritical Fluids 38 (2006) 146–166 163
[139] M.D. Macias-Sanchez, C. Mantell, M. Rodriguez, E. Martinez de la Ossa,L.M. Lubian, O. Montero, Supercritical fluid extraction of carotenoids andchlorophyll a from Nannochloropsis gaditana, J. Food Engrg. 66 (2005)245–251.
[140] A.P.R.F. Canela, P.T.V. Rosa, M.O.M. Marques, M.A.M. Meireles, Super-critical fluid extraction of fatty acids and carotenoids from the microalgaeSpirulina maxima, Ind. Eng. Chem. Res. 41 (2002) 3012–3018.
[141] J.O. Valderrama, M. Perrut, W. Majewski, Extraction of astaxantineand phycocyanine from microalgae with supercritical carbon dioxide,J. Chem. Eng. Data 48 (2003) 827–830.
[142] M. Hadolin, M. Skerget, Z. Knez, D. Bauman, High pressure extractionof vitamin E-rich oil from Silybum marianum, Food Chem. 74 (2001)355–364.
[143] J.R. Dean, B. Liu, Supercritical fluid extraction of Chinese herbalmedicines: investigation of extraction kinetics, Phytochem. Anal. 11(2000) 1–6.
[144] P. Tonthubthimthong, S. Chuaprasert, P. Douglas, W. Luewisutthichat,Supercritical CO2 extraction of nimbin from neem seeds—an experi-mental study, J. Food Engrg. 47 (2001) 289–293.
[145] P. Tonthubthimthong, P.L. Douglas, S. Douglas, W. Luewisutthichat, W.Teppaitoon, L. Pengsopa, Extraction of nimbin from neem seeds usingsupercritical CO2 and a supercritical CO2–methanol mixture, J. Supercrit.Fluids 30 (2004) 287–301.
[146] P. Ambrosino, R. Fresa, V. Fogliano, S.M. Monti, A. Ritieni, Extrac-tion of azadirachtin A from neem seed kernels by supercritical fluid andits evaluation by HPLC and LC/MS, J. Agric. Food Chem. 47 (1999)5252–5256.
[147] S. Johnson, E.D. Morgan, Supercritical fluid extraction of oil and triter-penoids from neem seeds, Phytochem. Anal. 8 (1997) 228–232.
[148] A. de Lucas, E. Martinez de la Ossa, J. Rincon, M.A. Blanco, I. Gracia,Supercritical fluid extraction of tocopherol concentrates from olive treeleaves, J. Supercrit. Fluids 22 (2002) 221–228.
[149] P. Bhattacharjee, A. Kshirsagar, R.S. Singhal, Supercritical carbon diox-ide extraction of 2-acetyl-1-pyrroline from Pandanus amaryllofoliusRoxb, Food Chem. 91 (2005) 255–259.
[150] H.G. Daood, V. Illes, M.H. Gnayfeed, B. Meszaros, G. Horvath, P.A.Biacs, Extraction of pungent spice paprika by supercritical carbondioxide and subcritical propane, J. Supercrit. Fluids 23 (2002) 143–152.
[151] E. Uquiche, J.M. del Valle, J. Ortiz, Supercritical carbon dioxide extrac-tion of red pepper (Capsicum annuum L.) oleoresin, J. Food Engrg. 65(2004) 55–66.
[152] D.K. Matabudul, N.T. Crosby, S. Sumar, A new and rapid method forthe determination of nicarbazin residues in poultry feed, eggs and muscletissue using supercritical fluid extraction and high performance liquidchromatography, Analyst 124 (1999) 499–502.
[153] G. Della Porta, E. Reverchon, Supercritical fluids extraction and fraction-ation of pyrethrins from pyrethrum, in: A. Bertucco (Ed.), Fourth Interna-tional Symposium on High Pressure Process Technology and ChemicalEngineering, Venice, Italy, 2002, p. 223.
[154] V. Louli, N. Ragoussis, K. Magoulas, Recovery of phenolic antioxi-dants from wine industry by-products, Biores. Technol. 92 (2004) 201–208.
[155] G. Perretti, E. Miniati, L. Montanari, P. Fantozzi, Improving thevalue of rice by-products by SFE, J. Supercrit. Fluids 26 (2003) 63–71.
[156] S. Lopez-Sebastian, E. Ramos, E. Ibanez, J.M. Bueno, L. Ballester, J.Tabera, G. Reglero, Dearomatization of antioxidant rosemary extractsby treatment with supercritical carbon dioxide, J. Agric. Food Chem. 46(1998) 13–19.
[157] E. Ibanez, A. Cifuentes, A.L. Crego, F.J. Senorans, S. Cavero, G. Reglero,Combined use of supercritical fluid extraction, micellar electrokineticchromatography, and reverse phase high performance liquid chromatogra-
phy for the analysis of antioxidants from rosemary (Rosmarinus officinalisL.), J. Agric. Food Chem. 48 (2000) 4060–4065.
[158] M.T. Tena, M. Valcarcel, P.J. Hidalgo, J.L. Ubera, Supercritical fluidextraction of natural antioxidants from rosemary: comparison with liquidsolvent sonication, Anal. Chem. 69 (1997) 521–526.
1 uperc
64 E. Reverchon, I. De Marco / J. of S
[159] M. Hadolin, A.R. Hras, D. Bauman, Z. Knez, Isolation and concentra-tion of natural antioxidants with high-pressure extraction, Inn. Food Sci.Emerg. Tech. 5 (2004) 245–248.
[160] Q. Hu, J. Xu, S. Chen, F. Yang, Antioxidant activity of extracts ofblack sesame seed (Sesamum indicum L.) by supercritical carbon dioxideextraction, J. Agric. Food Chem. 52 (2004) 943–947.
[161] J. Xu, S. Chen, Q. Hu, Antioxidant activity of brown pigment and extractsfrom black sesame seed (Sesamum indicum L.), Food Chem. 91 (2005)79–83.
[162] H. Rompp, C. Seger, C.S. Kaiser, E. Haslinger, P.C. Schmidt, Enrichmentof Hyperforin from St. John’s Wort (Hypericum perforatum) by pilot-scale supercritical carbon dioxide extraction, Eur. J. Pharm. Sci. 21 (2004)443–451.
[163] A. Smelcerovic, Z. Lepojevic, S. Djordjevic, Sub- and supercritical CO2-extraction of Hypericum perforatum L., Chem. Eng. Technol. 27 (2004)1327–1329.
[164] M.S. Gomez-Prieto, M.M. Caja, M. Herraiz, G. Santa-Maria, Supercrit-ical fluid extraction of all-trans-Lycopene from Tomato, J. Agric. FoodChem. 51 (2003) 3–7.
[165] N.L. Rozzi, R.K. Singh, R.A. Vierling, B.A. Watkins, Supercritical fluidextraction of Lycopene from tomato processing by-products, J. Agric.Food Chem. 50 (2002) 2638–2643.
[166] M. Ollanketo, K. Hartonen, M.-L. Riekkola, Y. Holm, R. Hiltunen, Super-critical carbon dioxide extraction of Lycopene in tomato skins, Eur. FoodRes. Technol. 212 (2001) 561–565.
[167] E. Sabio, M. Lozano, V. Montero de Espinosa, R.L. Mendes, A.P. Pereira,A.F. Palavra, J.A. Coelho, Lycopene and �-carotene extraction fromtomato processing waste using supercritical CO2, Ind. Eng. Chem. Res.42 (2003) 6641–6646.
[168] E. Cadoni, M.R. De Giorgi, E. Medda, G. Poma, Supercritical CO2 extrac-tion of Lycopene and �-carotene from ripe tomatoes, Dyes Pigments 44(2000) 27–32.
[169] T. Baysal, S. Ersus, D.A.J. Starmans, Supercritical CO2 extraction of �-carotene and Lycopene from tomato paste waste, J. Agric. Food Chem.48 (2000) 5507–5511.
[170] Y. Ge, H. Yan, B. Hui, Y. Ni, S. Wang, T. Cai, Extraction of natural vitaminE from wheat germ by supercritical carbon dioxide, J. Agric. Food Chem.50 (2002) 685–689.
[171] E. Reverchon, Mathematical modelling of supercritical extraction of sageoil, AIChE J. 42 (1996) 1765–1771.
[172] H. Sovova, Mathematical model for supercritical fluid extraction of natu-ral products and extraction curve evaluation, J. Supercrit. Fluids 33 (2005)35–52.
[173] M. Kandiah, M. Spiro, Extraction of ginger rhizomes: kinetic studieswith supercritical carbon dioxide, Int. J. Food Sci. Technol. 25 (1990)328–338.
[174] K. Nguyen, P. Barton, J. Spencer, Supercritical carbon dioxide of vanilla,J. Supercrit. Fluids 4 (1991) 40–46.
[175] K.D. Bartle, A.A. Clifford, S.B. Hawthorne, J.J. Langenfeld, D.J. Miller,R. Robinson, A model for dynamic extraction using a supercritical fluid,3 (1990) 143–149.
[176] E. Reverchon, G. Donsı, L. Sesti Osseo, Modeling of supercritical fluidextraction from herbaceous matrices, Ind. Eng. Chem. Res. 32 (1993)2721–2726.
[177] H. Sovova, R. Komers, J. Kucera, J. Jez, Supercritical carbon dioxideextraction of caraway essential oil, Chem. Eng. Sci. 49 (1994) 2499–2505.
[178] B.C. Roy, M. Goto, T. Hirose, Extraction of ginger oil with supercriticalcarbon dioxide: experiments and modeling, Ind. Eng. Chem. Res. 35(1996) 607–612.
[179] E. Reverchon, C. Marrone, Modeling and simulation of the supercriticalCO2 extraction of vegetable oils, J. Supercrit. Fluids 19 (2001) 161–175.
[180] E.M.C. Reis-Vasco, J.A.P. Coelho, A.M.F. Palavra, C. Marrone, E. Rever-
chon, Mathematical modelling and simulation of pennyroyal essential oilsupercritical extraction, Chem. Eng. Sci. 55 (2000) 2917–2922.
[181] E. Reverchon, G. Iacuzio, Supercritical desorption of bergamot peel oilfrom silica gel—experiments and mathematical modelling, Chem. Eng.Sci. 52 (20) (1997) 3553–3559.
ritical Fluids 38 (2006) 146–166
[182] E. Reverchon, Supercritical desorption of limonene and linalool fromsilica gel: experiments and modelling, Chem. Eng. Sci. 52 (6) (1997)1019–1027.
[183] E. Reverchon, G. Lamberti, P. Subra, Modelling and simulation of thesupercritical adsorption of complex terpene mixtures, Chem. Eng. Sci.53 (20) (1998) 3537–3544.
[184] C. Marrone, M. Poletto, E. Reverchon, A. Stassi, Almond oil extractionby supercritical CO2: experiments and modelling, Chem. Eng. Sci. 53(21) (1998) 3711–3718.
[185] N.T. Dunford, M. Goto, F. Temelli, Modeling of oil extraction with super-critical CO2 from Atlantic mackerel (Scomber scombrus) at differentmoisture contents, J. Supercrit. Fluids 13 (1998) 303–309.
[186] I. Goodarznia, M.H. Eikani, Supercritical carbon dioxide extraction ofessential oils: modelling and simulation, Chem. Eng. Sci. 53 (7) (1998)1387–1395.
[187] H. Sovova, M. Zarevucka, M. Vacek, K. Stransky, Solubility of two veg-etable oils in supercritical CO2, J. Supercrit. Fluids 20 (2001) 15–28.
[188] E. Reverchon, C. Marrone, Supercritical extraction of clove bud essentialoil: isolation and mathematical modelling, Chem. Eng. Sci. 52 (1997)3421–3428.
[189] A.B.A. de Azevedo, U. Kopcak, R.S. Mohamed, Extraction of fat fromfermented Cupuacu seeds with supercritical solvents, J. Supercrit. Fluids27 (2003) 223–237.
[190] E. Reverchon, J. Daghero, C. Marrone, M. Mattea, M. Poletto, Supercrit-ical fractional extraction of fennel seed oil and essential oil: experimentsand mathematical modelling, Ind. Eng. Chem. Res. 38 (1999) 3069–3075.
[191] J. Martinez, A.R. Monteiro, P.T.V. Rosa, M.O.M. Marques, M.A.A.Meireles, Multicomponent model to describe extraction of ginger ole-oresin with supercritical carbon dioxide, Ind. Eng. Chem. Res. 42 (2003)1057–1063.
[192] E. Reverchon, A. Kaziunas, C. Marrone, Supercritical CO2 extraction ofhiprose seed oil: experiments and mathematical modelling, Chem. Eng.Sci. 55 (2000) 2195–2201.
[193] J.M. del Valle, M. Jimenez, J.C. de la Fuente, Extraction kinetics of pre-pelletized Jalapeno peppers with supercritical CO2, J. Supercrit. Fluids25 (2003) 33–44.
[194] M. Akgun, N.A. Akgun, S. Dincer, Extraction and modelling of lavenderflower essential oil using supercritical carbon dioxide, Ind. Eng. Chem.Res. 39 (2000) 473–477.
[195] L.M.A.S. Campos, E.M.Z. Michielin, L. Danielski, S.R.S. Ferreira,Experimental data and modelling the supercritical fluid extraction ofmarigold (Calendula officinalis) oleoresin, J. Supercrit. Fluids 34 (2005)163–170.
[196] M.M. Esquivel, M.G. Bernardo-Gil, M.B. King, Mathematical models forsupercritical extraction of olive husk oil, J. Supercrit. Fluids 16 (1999)4–58.
[197] E. Reverchon, G. Della Porta, G. Lamberti, Modelling of orange flowerconcrete fractionation by supercritical CO2, J. Supercrit. Fluids 14 (1999)115–121.
[198] L.F. de Franca, M.A.M. Meireles, Modeling the extraction of carotene andlipids from pressed palm oil (Elaes guineensis) fibers using supercriticalCO2, J. Supercrit. Fluids 18 (2000) 35–47.
[199] V. Louli, G. Folas, E. Voutsas, K. Magoulas, Extraction of parsleyseed oil by supercritical CO2, J. Supercrit. Fluids 30 (2004) 163–174.
[200] S.R.S. Ferreira, M.A.M. Meireles, Modeling the supercritical fluid extrac-tion of black pepper (Piper nigrum L.) essential oil, J. Food Engrg. 54(2002) 263–269.
[201] S.M. Ghoreishi, S. Sharifi, Modeling of supercritical extraction of man-nitol from plane tree leaf, J. Pharm. Biomed. Anal. 24 (2001) 1037–1048.
[202] L. Teberikler, S.S. Koseoglu, A. Akgerman, Modeling of selec-tive extraction of phosphatidylcholine from a complex lecithin mix-
ture using supercritical CO2/ethanol, J. Food Lipids 10 (2003) 203–218.
[203] M. Perrut, J.Y. Clavier, M. Poletto, E. Reverchon, Mathematical modelingof sunflower seed extraction by supercritical CO2, Ind. Eng. Chem. Res.36 (1997) 430–435.
uperc
E. Reverchon, I. De Marco / J. of S
[204] H.K. Kiriamiti, E. Rascol, A. Marty, J.S. Condoret, Extraction rates of oilfrom high oleic sunflower seeds with supercritical carbon dioxide, Chem.Eng. Proc. 41 (2001) 711–718.
[205] H. Sovova, Rate of the vegetable oil extraction with supercritical CO2.I. Modelling of extraction curves, Chem. Eng. Sci. 49 (1994) 409–414.
[206] J. Stastova, J. Jez, M. Bartlova, H. Sovova, Rate of the vegetable oilextraction with supercritical CO2. III. Extraction from sea buckthorn,Chem. Eng. Sci. 51 (1996) 4347–4352.
[207] W. Wu, Y. Hou, Mathematical modeling of extraction of egg yolk oil withsupercritical CO2, J. Supercrit. Fluids 19 (2001) 149–159.
[208] E. Reverchon, M. Poletto, Mathematical modelling of supercritical CO2
fractionation of flower concretes, Chem. Eng. Sci. 51 (15) (1996)3741–3753.
[209] L. Sesti Osseo, E. Reverchon, G. Della Porta, Acetic acid–water fraction-ation by continuous packed tower processing with supercritical CO2, in:E. Reverchon (Ed.), Proceedings of the 6th Conference on SupercriticalFluids and Their Application, Maiori, Italy, 2001, p. 61.
[210] F.J. Senorans, A. Ruiz-Rodriguez, E. Ibanez, J. Tabera, G. Reglero, Opti-mization of counter-current supercritical fluid extraction conditions forspirits fractionation, J. Supercrit. Fluids 21 (2001) 41–49.
[211] F.J. Senorans, A. Ruiz-Rodriguez, E. Ibanez, J. Tabera, G. Reglero, Iso-lation of brandy aroma by counter-current supercritical fluid extraction,J. Supercrit. Fluids 26 (2003) 129–135.
[212] E. Reverchon, A. Marciano, M. Poletto, Fractionation of a peel oil keymixture by supercritical CO2 in a continuous tower, Ind. Eng. Chem. Res.36 (1997) 4940–4948.
[213] M. Budich, S. Heilig, T. Wesse, V. Leibkuchler, G. Brunner, Counter-current deterpenation of citrus oils with supercritical CO2, J. Supercrit.Fluids 14 (1999) 105–114.
[214] R. Ruivo, M.J. Cebola, P.C. Simoes, M. Nunes da Ponte, Fractionationof edible oil model mixtures by supercritical carbon dioxide in a packedcolumn. Part I: experimental results, Ind. Eng. Chem. Res. 40 (2001)1706–1711.
[215] R. Ruivo, M.J. Cebola, P.C. Simoes, M. Nunes da Ponte, Fractiona-tion of edible oil model mixtures by supercritical carbon dioxide in apacked column. 2. A mass-transfer study, Ind. Eng. Chem. Res. 41 (2002)2305–2315.
[216] O.J. Catchpole, J.B. Grey, K.A. Noermark, Fractionation of fish oil usingsupercritical CO2 and CO2 + ethanol mixtures, J. Supercrit. Fluids 19(2000) 25–37.
[217] V. Riha, G. Brunner, Separation of fish oil ethyl esters with supercriticalcarbon dioxide, J. Supercrit. Fluids 17 (2000) 55–64.
[218] L. Sesti Osseo, G. Caputo, I. Gracia, E. Reverchon, Continuous frac-tionation of used frying oil by supercritical CO2, J. Am. Oil Chem. Soc.(JAOCS) 81 (9) (2004) 879–885.
[219] J.W. King, E. Sagle-Demessie, F. Temelli, J.A. Teel, Thermal gradientfractionation of glyceride mixtures under supercritical fluid conditions,J. Supercrit. Fluids 10 (1997) 127–137.
[220] M. Poletto, L. Sesti Osseo, G. Della Porta, E. Reverchon, Hexane elimi-nation from soybean oil by continuous fractionation in a counter-currenttower by supercritical CO2, in: M. Perrut, E. Reverchon (Eds.), Proceed-ings of the 7th Meeting on Supercritical Fluids, Antibes, France, 2000, p.745.
[221] J. Tabera, A. Guinda, A. Ruiz-Rodriguez, F.J. Senorans, E. Ibanez, T.Albi, G. Reglero, Counter-current supercritical fluid extraction and frac-tionation of high-added-value compounds from a hexane extract of oliveleaves, J. Agric. Food Chem. 52 (2004) 4774–4779.
[222] O.J. Catchpole, P. Simoes, J.B. Grey, E.M.M. Nogueiro, P.J. Carmelo, M.Nunes da Ponte, Fractionation of lipids in a static mixer and packed col-umn using supercritical carbon dioxide, Ind. Eng. Chem. Res. 39 (2000)4820–4827.
[223] A.M. Hurtado-Benavides, F.J. Senorans, E. Ibanez, G. Reglero, Counter-
current packed column supercritical CO2 extraction of olive oil. Masstransfer evaluation, J. Supercrit. Fluids 28 (2004) 29–35.
[224] H. Kubat, U. Akman, O. Hortacsu, Semi-batch packed-column deterpe-nation of origanum oil by dense carbon dioxide, Chem. Eng. Proc. 40(2001) 19–32.
ritical Fluids 38 (2006) 146–166 165
[225] F.J. Senorans, A. Ruiz-Rodriguez, S. Cavero, A. Cifuentes, E. Ibanez, G.Reglero, Isolation of antioxidant compounds from orange juice by usingcounter-current supercritical fluid extraction (CC-SFE), J. Agric. FoodChem. 49 (2001) 6039–6044.
[226] C. Simo, E. Ibanez, F.J. Senorans, C. Barbas, G. Reglero, A. Cifuentes,Analysis of antioxidants from orange juice obtained by counter-currentsupercritical fluid extraction, using micellar electrokinetic chromatogra-phy and reverse-phase liquid chromatography, J. Agric. Food Chem. 50(2002) 6648–6652.
[227] O.J. Catchpole, J.-C. von Kamp, J.B. Grey, Extraction of squalene fromshark liver oil in a packed column using supercritical carbon dioxide, Ind.Eng. Chem. Res. 36 (1997) 4318–4324.
[228] R. Ruivo, A. Paiva, J.P.B. Mota, P. Simoes, Dynamic model of a counter-current packed column operating at high pressure conditions, J. Supercrit.Fluids 32 (2004) 183–192.
[229] B. Ramchandran, J.B. Riggs, H.R. Heichelheim, A.F. Seibert, J.R. Fair,Dynamic simulation of a supercritical fluid extraction process, Ind. Eng.Chem. Res. 31 (1992) 281.
[230] S. Camy, J.-S. Condoret, Dynamic modelling of a fractionation processfor a liquid mixture using supercritical carbon dioxide, Chem. Eng. Proc.40 (2001) 499–509.
[231] F. Benvenuti, F. Gironi, Dynamic simulation of a semicontinuous extrac-tion process using supercritical solvent, in: A. Bertucco (Ed.), Proceedingsof the 5th Italian Conference on Supercritical Fluids and their Applica-tions, 1999, p. 281.
[232] G. Cesari, M. Fermeglia, I. Kikic, M. Policastro, A computer-programfor the dynamic simulation of a semi-batch supercritical fluid extractionprocess, Comput. Chem. Eng. 13 (1989) 1175–1181.
[233] O.J. Catchpole, J.B. Grey, K.A. Mitchell, J.S. Lan, Supercritical anti-solvent fractionation of propolis tincture, J. Supercrit. Fluids 29 (2004)97–106.
[234] O.J. Catchpole, C. Bergmann, Continuous gas anti-solvent fractiona-tion of natural products, in: M. Perrut, P. Subra (Eds.), Proceedingsof the 5th Meeting on Supercritical Fluids, vol. 1, Nice, France, 1998,p. 257.
[235] O.J. Catchpole, S. Hochmann, S.R.J. Anderson, Gas antisolvent fraction-ation of natural products, in: R. von Rohr, Ch. Trepp (Eds.), Proceedingsof the 12th High Pressure Engineering on Process Technology, Elsevier,Amsterdam, 1996, p. 309.
[236] M.B.O. Andersson, M. Demirbuker, L.G. Blomberg, Semi-continuousextraction/purification of lipids by means of supercritical fluids, J. Chro-matogr. A 785 (1997) 337–343.
[237] M. Mukhopadhyay, S. Singh, Refining of crude lecithin using densecarbon dioxide as anti-solvent, J. Supercrit. Fluids 30 (2004) 201–211.
[238] S. Scrugli, M. Frongia, M. Muscas, P. Madau, G. Loi, G. Sfacteria, D.Carta, I. De Marco, E. Reverchon, A preliminary study on the applica-tion of supercritical antisolvent technique to the fractionation of tobaccoextracts, in: M. Besnard, F. Cansell (Eds.), Proceedings of the 8th Meetingon Supercritical Fluids, Bordeaux, France, 2002, p. 901.
[239] N.T. Dunfold, F. Temelli, Extraction of canola phospholipids with super-critical CO2 and ethanol, in: Proceedings of the 3rd International Sym-posium on Supercritical Fluids, vol. 3, Strassbourg, France, 1994, p. 471.
[240] L. Montanari, P. Fantozzi, J.M. Schneider, J.W. King, Selective extractionof phospholipids from soybean with supercritical CO2 and ethanol, J.Supercrit. Fluids 14 (2) (1999) 87–93.
[241] M. Mukhopadhyay, Natural Extracts Using Supercritical Carbon Dioxide,vol. 10, CRC Press, Boca Raton, FL, 2000, pp. 280–293 (Chapter 10).
[242] M. Mukhopadhyay, Purification of phytochemicals by selective crystal-lization using carbon dioxide as anti-solvent, in: Proceedings of the 10thInternational Symposium on Supercritical Fluid Chromatography, Extrac-tion and Processing, Myrtle Beach, SC, USA, 2001.
[243] J.C. Chang, A.D. Randolph, N.E. Craft, Separation of beta-carotene mix-
tures precipitated from liquid solvents with high-pressure CO2, Biotech-nol. Prog. 7 (1991) 275.
[244] A. Martin, M.J. Cocero, Numerical modeling of jet hydrodynamics, masstransfer, and crystallization kinetics in the supercritical antisolvent (SAS)process, J. Supercrit. Fluids 32 (2004) 203–219.
1 uperc
66 E. Reverchon, I. De Marco / J. of S
[245] N. Elvassore, T. Parton, A. Bertucco, V. Di Noto, Kinetics of particle
formation in the gas antisolvent precipitation process, AIChE J. 49 (4)(2003) 859–868.
[246] M. Lora, A. Bertucco, I. Kikic, Simulation of the semicontinuous super-critical antisolvent recrystallization process, Ind. Eng. Chem. Res. 39(2000) 1487–1496.
ritical Fluids 38 (2006) 146–166
[247] J.O. Werling, P.G. Debenedetti, Numerical modeling of mass transfer
in the supercritical antisolvent process, J. Supercrit. Fluids 16 (1999)167–181.
[248] J.O. Werling, P.G. Debenedetti, Numerical modeling of mass transfer inthe supercritical antisolvent process: miscible conditions, J. Supercrit.Fluids 18 (2000) 11–24.
