J.

of Supercritical Fluids 38 (2006) 146166

Review

Supercritical uid extraction and fractionation of natural matter

Ernesto Reverchon , Iolanda De Marco
Universit` di Salerno, Dipartimento di Ingegneria Chimica ed Alimentare, Via Ponte don Melillo, 84084 Fisciano (SA), Italy a Received 30 June 2005; received in revised form 13 March 2006; accepted 13 March 2006

Abstract Supercritical extraction and fractionation of natural matter is one of the early and most studied applications in the eld of supercritical uids. In the last 10 years, studies on the extraction of classical compounds like essential and seed oils from various sources: seeds, fruits, leaves, owers, rhizomes, etc., with or without the addition of a co-solvent have been published. Supercritical extraction of antioxidants, pharmaceuticals, colouring matters, and pesticides has also been studied. The separation of liquid mixtures and the antisolvent extraction are other processes that can perform very interesting separations. Mathematical modelling has also been developed and rened 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 uids extraction and fractionation. 2006 Elsevier B.V. All rights reserved.
Keywords: Supercritical extraction; Liquid fractionation; Purication; Antisolvent extraction; Modelling

Contents
1. 2. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Solids processing. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1. Selection of the operating parameters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2. Examples of application . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2.1. Essential oils extraction/isolation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2.2. Seed oils extraction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3. High added value compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3.1. Nutraceuticals: Lycopene and Astaxanthin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3.2. Pharmaceuticals: Hyperforin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3.3. Pesticides: Pyrethrins and Azadirachtins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4. Mathematical modelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Liquid feed processing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1. Selection of the operating parameters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2. Examples of application . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2.1. Hexane elimination from seed oils . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2.2. Fried oil fractionation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3. Mathematical modelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Antisolvent extraction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1. Selection of the operating parameters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2. Examples of application . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2.1. Lecithin extraction from soybean oil . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147 148 148 149 149 149 149 150 153 153 154 157 157 157 157 158 158 158 158 158 158

3.

4.

Corresponding author. Tel.: +39 089 964116; fax: +39 089 964057. E-mail address: ereverchon@unisa.it (E. Reverchon).

0896-8446/$ see front matter 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.supu.2006.03.020

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147

5.

4.2.2. Propolis tincture fractionation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2.3. Proteins extraction from tobacco . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3. Mathematical modelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conclusions and perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

159 159 159 159 160

1. Introduction Extraction of compounds from natural sources is the most widely studied application of supercritical uids (SCFs) with several hundreds of published scientic papers. Indeed, supercritical uids extraction (SFE) has immediate advantages over traditional extraction techniques: it is a exible process due to the possibility of continuous modulation of the solvent power/selectivity of the SCF, allows the elimination of polluting organic solvents and of the expensive post-processing of the extracts for solvent elimination. Several compounds have been examined as SFE solvents. For example, hydrocarbons such as hexane, pentane and butane, nitrous oxide, sulphur hexauoride and uorinated hydrocarbons [1]. However, carbon dioxide (CO2 ) is the most popular SFE solvent because it is safe, readily available and has a low cost. It allows supercritical operations at relatively low pressures and at near-room temperatures. The only serious drawback of SFE is the higher investment costs if compared to traditional atmospheric pressure extraction techniques. However, the base process scheme (extraction plus separation) is relatively cheap and very simple to be scaled up to industrial scale. SFE works have been the subject of several reviews [210]. Therefore, we will limit time interval of our analysis to the last decade (1996 to present time), presenting rst a summary of the concepts and results that we consider as well established in the literature [2]. Early works on SFE frequently used high pressures (>350 bar) even when relatively supercritical CO2 (SC-CO2 ) soluble compounds had to be extracted (for example: terpenes, sesquiterpenes, fatty acids, etc.). Operating in this manner, only the solvent power of the SCF was enhanced. Then, the concept of the optimization between solvent power and selectivity has been applied and SFE operating conditions have been chosen to obtain the selective extraction of the compounds of interest, reducing to a minimum the co-extraction of undesired compounds [2]. For successful extraction, not only the solubility of the compounds to be extracted and/or of the undesired compounds has to be taken into account; mass transfer resistances due to the structure of the raw material and to the specic location of the compounds to be extracted can also play a relevant role. A microscopic analysis of the natural structure can help in understanding where mass transfer resistances are located. Specic experiments performed varying particle size and supercritical solvent residence time can also be helpful in this sense. The complex interplay between thermodynamics (solubility) and kinetics (mass transfer) has to be understood to properly perform SFE. Fractional separation of the extracts is another well-known concept that can be useful to improve the SFE process selectiv-

ity. In several cases, it is not possible to avoid the co-extraction of some compound families (with different solubilities, but also with different mass transfer resistances in the raw matter). In these cases, it is possible to perform an extraction in successive steps at increasing pressures to obtain the fractional extraction of the soluble compounds contained in the organic matrix, selected by decreasing solubilities in the supercritical solvent. Fractional separation allows the fractionation of the SCF extracts, operating the plant with some separators in series at different pressures and temperatures. The scope of this operation is to induce the selective precipitation of different compound families as a function of their different saturation conditions in the SCF. For example, this procedure has been applied in the SFE of essential oils [1116]. In several cases, the starting material is a liquid mixture. The process to be applied is the continuous liquid extraction performed in a packed tower. It is worth of note that, while the extraction from solids is a discontinuous operation, the packed tower is capable of continuous steady state operation that allows the processing of large quantities of liquid mixtures in a relatively small apparatus and in a short time. In some other cases, the material to be treated is a liquid mixture that contains solid compounds dissolved in it. The extraction of these compounds from the liquid solution cannot be performed in a packed tower since the solid matter will precipitate on the packings and xed bed extraction is not possible. In this case, a supercritical antisolvent extraction (SAE) process has to be adopted. The pre-conditions to apply antisolvent extraction are similar to the ones characteristics of supercritical antisolvent micronization (SAS): the liquid solvent has to be very soluble in SC-CO2 , whereas, the solids have to be completely not soluble in the SCF. The scope of the process is not the micronization, but the selective extraction of the solid compounds. These conditions can be frequently obtained since many organic solvents are readily soluble in SC-CO2 even at mild operating conditions and many high molecular weight solids show negligible solubilities in SC-CO2 especially at low CO2 densities. Due to the structural complexity and variability (with the season, kind, crop, etc.) of the materials to be treated and to the large variety of compounds that can be extracted (different molecular weight, polarity, link with the structure, etc.), these processes are far from to be considered exhaustively studied, though some industrial applications have been already developed. Moreover, an increasing interest has been registered in the extraction of high added value substances, such as antioxidants, pharmaceuticals and colouring matters. Therefore, the scope of this review is to analyze SFE, SAE and liquid fractionation studies performed in the last 10 years, considering the evolution of the extraction processes, products

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and materials treated. A critical analysis will be performed and the perspectives of the eld will be illustrated. 2. Solids processing It is the most studied SCF application since the most frequently required separation process is the extraction/elimination of one or more compound families from a solid natural matrix. The basic extraction scheme consists of an extraction vessel charged with the raw matter to be extracted. As a rule, the starting material is dried and grinded to favour the extraction process. It is loaded in a basket located inside the extractor that allows fast charge and discharge of the extraction vessel. The SCF at the exit of the extractor ows through a depressurization valve to a separator in which, due to the lower pressure, the extracts are released from the gaseous medium and collected. More sophisticated extraction schemes contain two or more separators. In this case, it is possible to fractionate the extract in two or more fractions of different composition by setting opportune temperatures and pressures in the separators [1734]. Solids pre-processing is also a parameter that can largely inuence the separation performance. For example, solid drying, aking and particle size optimization have, as a rule, be taken into account. Other possible variations of the SFE processing scheme are: multistage extraction and co-solvents addition. Multi-step operation is obtained varying pressure and/or temperature in each process step [35,36]. This strategy can be used when it is required the extraction of several compound families from the same matrix and they show different solubilities in SC-CO2 . It takes advantage of the fact that SC-CO2 solvent power can be continuously varied with pressure and temperature. For example, it is possible to perform a rst extraction operating at low CO2 density (e.g., 0.29 g/cm3 , 90 bar, 50 C) followed by a second extraction step at high CO2 density (e.g., 0.87 g/cm3 , 300 bar, 50 C). The most soluble compounds are extracted during the rst step (for example, essential oils) and the less soluble in the second one (e.g., antioxidants) [3740]. A liquid co-solvent can be added to SC-CO2 to increase its solvent power towards polar molecules. Indeed, SC-CO2 is a good solvent for lipophilic (non-polar) compounds, whereas, it has a low afnity with polar compounds. Various authors added small quantities of liquid solvents (for example, ethyl alcohol) that are readily solubilized by SC-CO2 . When in solution, they modify the solvent power of SC-CO2 [28,32,4075]. This strategy has the drawback that, a larger solvent power could also mean lower process selectivity and since, as a rule, the cosolvent is liquid at atmospheric pressure, it will be collected in the separator together with the extracted compounds. Subsequent processing for solvent elimination is required; therefore, one of the advantages of the SFE; i.e., solventless operation is lost. Another possible process arrangement is the continuous feeding and discharging of the solid to obtain the continuous processing of the solid matter [76]. This operation is possible adding two solid extruders at the top and at the bottom of the extractor and can avoid the use of two or more extractors to simu-

late continuous solid processing; however, design and operation of the two extruders is not cheap and simple. 2.1. Selection of the operating parameters The selection of the operating conditions depends on the specic compound or compound family to be extracted. Molecular weight and polarity have to be taken into account case by case; but some general rules can be applied. First of all, SFE temperature for thermolabile compounds has to be xed between 35 and 60 C; e.g., in the vicinity of the critical point and as low as possible to avoid degradation. The increase of temperature reduces the density of SC-CO2 (for a xed pressure) thus reducing the solvent power of the supercritical solvent; but it increases the vapor pressure of the compounds to be extracted. Therefore, the tendency of these compounds to pass in the uid phase is increased. However, the most relevant process parameter is the extraction pressure that can be used to tune the selectivity of the SCF. The general rule is: the higher is the pressure, the larger is the solvent power and the smaller is the extraction selectivity. Frequently, the solvent power is described in terms of the SC-CO2 density at the given operating conditions. CO2 density can vary from about 0.15 to 1.0 g/cm3 and is connected to both pressure and temperature. Its variation is strongly non-linear; therefore, the proper selection requires the use of accurate tables of CO2 properties [77,78]. The other crucial parameters in SFE are CO2 ow rate, particle size of the matrix and duration of the process (extraction time). The proper selection of these parameters has the scope of producing the complete extraction of the desired compounds in the shorter time. They are connected to the thermodynamics (solubility) and the kinetics of the extraction process in the specic raw matter (mass transfer resistances). The proper selection depends on the mechanism that controls the process: the slowest one determines the overall process velocity. CO2 ow rate is a relevant parameter if the process is controlled by an external mass transfer resistance or by equilibrium: the amount of supercritical solvent feed to the extraction vessel, in this case, determines the extraction rate. Particle size plays a determining role in extraction processes controlled by internal mass transfer resistances, since a smaller mean particle size reduces the length of diffusion of the solvent. However, if particles are too small, they can give problems of channelling inside the extraction bed. Part of the solvent ows through channels formed inside the extraction bed and does not contact the material to be extracted thus causing a loss of efciency and yield of the process. As a rule, particles with mean diameters ranging approximately between 0.25 and 2.0 mm are used. The optimum dimension can be chosen case by case considering water content in the matrix and the quantity of extractable liquid compounds that can produce phenomena of coalescence among the particles thus favouring the irregular extraction along the extraction bed. Moreover, the production of very small particles by grinding could produce the loss of volatile compounds. Process duration is interconnected with CO2 ow rate and particle size and has to be properly selected to maximize the yield of the extraction process.

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2.2. Examples of application Some well established industrial processes use SFE to produce hops extracts, decaffeinated coffee and some food nutritional substances that offer also some aspects of therapeutic protection to the human body (nutraceuticals). However, many other applications are possible. 2.2.1. Essential oils extraction/isolation This process has been widely studied. Essential oils are mainly formed by hydrocarbon and oxygenated terpenes and by hydrocarbon and oxygenated sesquiterpenes. They can be extracted from seeds, roots, owers, herbs and leaves using the so-called hydrodistillation. This is a very simple process, but suffers of many drawbacks: thermal degradation, hydrolysis and solubilization in water of some compounds that alter the avour and fragrance prole of many essential oils extracted by this technique. From the point of view of SFE, essential oils isolation is an example of extraction plus fractional separation. Indeed, this process can be optimally performed operating at mild pressures (from 90 to 100 bar) and temperatures (from 40 to 50 C) since at these process conditions all the essential oil components are largely soluble in SC-CO2 [7982]. For example, linalool, a typical oxygenated terpene is completely miscible with SCCO2 at pressures larger than about 85 bar when the temperature is set at 40 C [83]. Essential oils are at least partly located inside the vegetable structure; therefore, mass transfer resistances have to be considered too. At the previously discussed operating conditions, essential oil components are extracted together with cuticular waxes; i.e., parafnic compounds located on the surface of vegetable matter with the scope of controlling perspiration. Parafns exhibit a relatively low solubility at these operating conditions [84]; but, of course, if the extraction pressure is increased their contribution in the extract will be more relevant; other compounds (like fatty acids) could be also increasingly extracted. Therefore, extraction of waxes is controlled by their solubility and essential oil extraction is controlled, at least in part, by internal mass transfer resistances in the vegetable structure. As a result of these interactions, the two compound families (essential oil and waxes) are co-extracted at all operating conditions. To selectively extract the essential oil alone, it is necessary to take advantage of the fact that at low temperatures (from 5 to +5 C) waxes are practically insoluble in CO2 , whereas, the other compounds maintain very large solubilities. Therefore, it is possible to fractionate the extract operating, for example, the extraction at 90 bar, 40 C and, then, performing a rst separation, for example, at 0 C, 90 bar, and a second separation at 15 C and 20 bar. In this manner, in the rst separator the selective precipitation of waxes is obtained and no precipitation of the other extracted compounds occurs, whereas, in the second separator, essential oil is recovered. An industrial plant (V = 1200 dm3 ) that uses this process arrangement has been constructed and successfully operated (Essences, Italy). It is not possible to perform the extraction directly at 0 C and 90 bar, since the vegetable matter contains many other compound families (antioxidants, colours, etc.) that are soluble at

these process conditions and, therefore, a complex mixture of essential oil plus these other compounds is obtained. Data on essential oils supercritical extraction is shown in Table 1 that is alphabetically organized by the common name (raw material), the botanical name and the target component (the extract). In Table 1, laboratory, pilot plant and analytical studies performed using very small extractors are included. Only in some of them, the operating conditions have been optimized to maximize both the total yield and the selectivity of the process; therefore, yield and the operating conditions can be largely inuenced by the nal scope of the paper: to selectively obtain the essential oil, or to extrapolate its composition from the unfractionated extract (concrete). An analysis on the inuence of some process parameters such as pressure, temperature, extraction time, percentage of co-solvents and solvent ow rates is available in some of the papers considered in Table 1. 2.2.2. Seed oils extraction Vegetable oil from seeds is traditionally produced by hexane extraction from ground seeds. The process is very efcient, but its major problem is represented by hexane elimination after extraction. Three distillation units in series, operated under vacuum and other ancillary apparatuses (deodorizer, degumming, etc.), have to be used. The possible thermal degradation of the oil and the incomplete hexane elimination (from 500 to 1000 ppm residue) are the drawbacks of this process. Therefore, several authors have proposed the substitution of the traditional process by SC-CO2 extraction of oil from seeds [22,28,41,68,71,8589] (see Table 1). Indeed, triglycerides forming seed oils are readily soluble in SC-CO2 at 40 C and at pressures larger than about 280 bar. The main parameters to be taken into account for this process are particle size, pressure and residence time. Small particles (1 mm mean diameter or less) and high pressures (300500 bar) can strongly reduce the extraction time. After extraction, the SC-CO2 tryglicerides solution is sent to a separator working at subcritical conditions. This operation reduces to near zero the solvent power of CO2 and allows the recovery of oil. The complete elimination of gaseous CO2 from oil is also obtained in the separator. The SFE of several seed oils has been successfully performed up to the pilot scale. An alternative process has also been proposed, in which the extraction is performed at a xed pressure and only temperature variations are used to reduce the oil solubility and obtain its recovery. The advantage of this scheme coupled to heat exchangers networking is in the reduction of energy consumption in the overall extraction process [90]. 2.3. High added value compounds The list of high added value compounds (mainly nutraceuticals and pharmaceuticals) is reported in Table 2. A large spectrum of compounds can be inserted in these categories, since food additives with nutritional and pharmaceutical properties (nutraceuticals) range from tocopherols to carotenoids to alkaloids to unsatured fatty acids. Pharmaceutical compounds like Artemisinin (antimalaric drug), to Hyperforin (antidepressant drug), to sterols can be extracted from various matters. Pesticides

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Table 1 SFE of oleoresins (OR), essential (EO), volatile (VO) and seed (SO) oils Raw material Anise seeds Bacuri fruit shells Basil leaves Borage seeds Cashew Celery roots Chamomile owers Clove bud Coriander seeds Eucalyptus leaves Fennel seeds Grape seeds Hiprose seeds Juniper fruits Laurel leaves Lemon balm Lemon bergamot Lemon eucalyptus Lemongrass leaves Lovage leaves and roots Marjoram leaves Mint leaves Oregano Palm kernel oil Pennyroyal Pepper, black Pepper, red Rye bran Sage leaves Spiked thyme Star anise Thyme Tuberose concrete Vernonia seeds Botanical name Pimpinella anisum L. Platonia insignis Mart. Ocimum basilicum Borage ofcinalis L. Anacardium occidentale Apium graveolens L. Chamomilla recutita L. R. Eugenia caryophyllata Coriandrum satium L. Eucalyptus globulus L. Foeniculum vulgare Mill. Vitis vinifera Rosa canina L. Juniperus communis L. Laurus nobilis Melissa ofcinalis Monarda citriodora Eucalyptus citriodora Cymbopogon citrates Levisticum ofcinale Koch. Origanum majorana Mentha spicata insularis Origanum vulgare L. Elaeis guineensis Mentha pulegium L. Piper nigrum L. Capsicum frutescens L. Secale cereale Salvia desoleana Thymbra spicata Illicium anisatum Thyme zygis sylvestris Nepeta Tuberosa L. Vernonia galamensis Extract EO EO EO SO VO SO EO and OR EO SO EO SO SO SO VO EO EO EO EO EO EO EO EO EO SO EO EO OR Alkylresorcinols EO EO EO EO EO SO References [91] [92] [69,93] [41,85] [36,94] [28,86] [95] [19] [87] [17] [22] [59] [68,88,89] [96] [20] [22,27,97] [97] [97] [97,98] [28,69,99,100] [101] [21,93] [67,69,93,102,103] [104,105,106] [56] [107,108] [109] [73] [21,69] [110] [19] [111] [18] [71]

or insecticide principles are widely diffused in the vegetable matter and, if extracted by SFE could be used in the biological agriculture. Another kind of extraction process is the elimination of pollutants and pesticides from natural matter in which they obviously exert a detrimental effect. These products are outside the scopes of this work; but, they represent another interesting application of SFE [65,66,112]. In the following, some relevant cases, that have been recently studied, are discussed in the detail. 2.3.1. Nutraceuticals: Lycopene and Astaxanthin Carotenoids are a large family of compounds that possess antioxidant and colouring properties and are investigated for food, cosmetic and medical applications. They are contained in a large variety of natural sources: vegetables, animals, bacteria, yeasts, microalgae. Traditional carotenoids extraction is performed by organic solvents with the well-known problems of selectivity and organic solvents usage and pollution. Pretreatments of the starting material play a relevant role in the efciency of the extraction process: crushing, freeze drying, enzymatic cell degradation have been proposed. The problem is to reduce the internal mass transfer resistance that opposes a

strong obstacle to extraction, since these materials are very frequently located well inside complex cellular structures and can also be linked to the solid matrix. Their extraction by SCFs from various sources has been studied by several authors [25,32,53,63,64,72,118,136,138 140,150,151,164169]. Depending on the particular compound studied (molecular weight and number of polar bounds), they show very low or moderate solubilities in SC-CO2 . Therefore, in several cases SC-CO2 added with a co-solvent has been proposed as the supercritical extraction medium. The most frequently proposed co-solvent is ethyl alcohol since its presence (in traces) in the nal extracts does not compromise the use in nutraceutical or pharmaceutical applications. However, it is better, when it is possible, to avoid the use of a liquid co-solvent that tends to repropose the problem of solvent elimination from the extracts. Most carotenoids are polyunsaturated hydrocarbons containing 40 carbon atoms and two terminal ring systems. Carotenoids that are composed entirely of carbon and hydrogen are called carotenes, whereas, those that also contain oxygen are called xanthopylls. Lycopene is a carotene with relevant antioxidant properties and can have a protective effect against various chronic illnesses (like coronary heart disease and cancer). The major sources of

E. Reverchon, I. De Marco / J. of Supercritical Fluids 38 (2006) 146166 Table 2 SFE of high added value compounds Raw material Aloe vera leaves Animal liver Anise verbena Apricot pomace Artemisia Boldo leaves Bupleuri radix Buriti fruit Cape ash Chamomile China smilax Cocoa beans Cocoa beans Cocoa beans Coffee powder Coneower Coriander seeds Crustaceans Dandelion leaves Dill Espinheira Santa Eucalyptus leaves Feverfew Fresh bay Ginger Ginkgo Green tea Guaran` seeds a Hawthorn Horsetail Indian almond leaves Kava roots and steams Marigold Marjoram Marjoram Mat` leaves e Mexican sunower Microalgae Microalgae Microalgae Microalgae Microalgae Microalgae Microalgae Milk Thistle Moso-Bamboo Moutan Neem seeds Olive leaves Olive tree leaves Onion Pandanus mealybug Paprika Parsley Botanical name Aloe barbadensis Miller Lippia alba Prunus armeniaca Artemisia annua L. Peamus boldus M. Bupleurum kaoi Liu Mauritia exuosa Ekebergia capensis Sparrm. Matricaria recutita Smilax china L. Theobroma cacao Theobroma cacao Theobroma cacao Coffea arabica Echinacea angustifolia Coriandrum sativum Extract -Tocopherol Benzimidazoles Limonene and carvone -Carotene Artemisinin Boldine Saikosponins Carotenoids and lipids Oleanolic acid and 3-epioleanolic acid Flavonoids and terpenoids Sapogenins Caffeine, theobromine Methylxanthines Cocoa butter Coffee aroma Alkylamides Tocopherols, avonoids and terpenoids Astaxanthin -Amyrin and -sitosterol Tocopherol Squalene, vitamin E, Stigmasterol Gallic and ellagic acids Parthenolide Tocopherol Gingerols and shogaols Ginkgolides and avonoids Catechins Caffeine Flavonoids and terpenoids Oleoresin Squalene Lactones Flavonoids and terpenoids Carotenoids and chlorophylls Phenolic and Triterpenoid antioxidants Caffeine, Vitamine E, theobromine and stigmasterol Tagitinin C Alkadienes Canthaxanthin and Astaxanthin Carotenoids and chlorophyll Carotenoids and fatty acids -Carotene -Linolenic acid Astaxantine and phycocyanine Tocopherol Ethoxyquin A, sesquiterpene A and cyclohexanone A Paeonol Nimbin, salannin and azadirachtin Polyphenols Tocopherol Onion avour 2-Acetyl-1-pyrroline Carotenoids, tocopherols and capsaicinoids Tocopherol

151

References [51] [113] [114,115] [72] [116] [44,117] [31] [118] [119] [54] [61] [120] [53] [121] [122] [123] [124] [125] [126] [127] [128] [45] [129] [127] [46,47] [60,70] [58] [53,130] [54] [131] [132,133] [62] [54] [25] [134,135] [53,136] [137] [138] [138] [139] [140] [138] [138] [141] [142] [52] [143] [144147] [43] [148] [24] [149] [150,151] [127]

Taraxacum ofcinale Anethum graveolens Maytenus ilicifolia Eucalyptus camaldulensis var. brevirostris Tanacetum parthenium Laurus nobilis Zingiber ofcinale Roscoe Ginkgo biloba L. Cratoxylum prunifolium Paullinia cupana Crataegus sp. Equisetum giganteum L. Terminalia catappa L. Piper methysticum Calendula ofcinalis Origanum majorana L. Origanum majorana L. Ilex paraguariensis Tithonia diversifolia Botryococcus braunii Chlorella vulgaris Nannochloropsis gaditana Spirulina maxima Dunaliella salina Arthrospira maxima Haematococcus pluvialis Silybum marianum Phyllostachys heterocycla Paeonia suffruticosa Azadirachta indica A. Juss Olea europa Olea europa Allium cepa L. Pandanus amaryllifolius Roxb. Capsicum annuum L. Petroselinum crispum

152 Table 2 (Continued ) Raw material Poultry feed, eggs and muscle tissue Propolis Pyrethrum ower Red grape pomace Red yeast Rice Rosemary Sage Savory Saw Palmetto berries Sesame seeds, black Soybean our Soybean lecithin Spearmint St. Johns Wort St. Johns Wort St. Johns Wort owers Stevia leaves Stinging nettle Sweet grass

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Botanical name Resina propoli Chrysanthemum cinerariifolium Vitis vinifera Agiorgitiko Phafa rhodozyma

Extract Nicarbazin Flavonoids, galangin and caffeic acid phenethyl ester Pyrethrins Phenolic antioxidants Astaxanthin Tocopherols, tocochromanols and oryzanols Rosmanol, carnosic acid and carnosol Carnosolic acid Oil Fatty acids and -sitosterol Sesamol, sesaminol and -tocopherol Isoavones Phosphatidylcholine Tocopherol Hyperforin Phloroglucinols Hyperforin and Adhyperforin Glycosides Carotenoids and chlorophylls 5,8-Dihydroxycoumarin and 5-hydroxy-8-O- -dglucopyranosyl-benzopyranone Lycopene Lycopene and -carotene Curcumin and curcuminoids Vitamin E Deoxyschisandrin

References [152] [30] [33,34,153] [154] [64] [155] [3739,42,47,156159] [29] [26] [62] [160,161] [50] [74,75] [127] [162,163] [57] [62] [49] [63] [40]

Rosmarinus ofcinalis L. Salvia ofcinalis L. Satureja hortensis L. Serenoa repens Sesamum indicum L. Glycine max Glycine max Mentha spicata Hypericum perforatum L. Hypericum perforatum L. Hypericum perforatum L. Stevia rebaudiana Bertoni Urtica dioica L. Hierochloe odorata

Tomato Tomato Turmeric Wheat germ Wu-wei-zi

Lycopersicon esculentum Lycopersicon esculentum Curcuma longa L. Triricum aestivum Schisandra chinensis

[32,16,46,162] [167169] [47,48] [170] [143]

Lycopene are ripe tomatoes, tomato products and by products (skins). SFE of Lycopene has been performed using pure SCCO2 [164,167] and with co-solvents [32,166,168,169]. The use of appropriate co-solvents (acetone [166], ethanol [169], chloroform [168], seed oil [32]) increases the extraction rate but has, as a rule, a negligible inuence on the nal yield of Lycopene. Therefore, using pure SC-CO2 at higher pressures can be sufcient to compensate the absence of co-solvent and has the advantage of producing a solvent free extract. At pressures lower than about 250 bar, operating at 40 C, the extraction of Lycopene is negligible [168]. The yield largely increases with pressure due to the increase of Lycopene solubility in the supercritical solvent. From the analysis of the literature, the parameter that mainly controls Lycopene extraction is the extraction temperature. Indeed, several authors [32,165168] found a very strong increase of Lycopene yield with temperature and decided to operate up to a maximum of 110 C, as shown in Fig. 1 [166]. This effect is surprising since they did not nd a similar dependence on temperature for the extraction of -carotene that is also contained in tomato products [167]. The authors tried to explain this dependence on temperature considering the increase of SC-CO2 diffusivity with temperature and an increase of Lycopene vapor pressure; but no explanation seems completely convincing. Lycopene is contained into vegetable structures called chromoplasts in form of large crystals.

Therefore, its extraction can be difcult due to strong internal mass transfer resistances. It is possible that an increase of extraction temperature contributes to the degradation of chromoplasts.

Fig. 1. Relative recoveries of Lycopene from tomato skins at different temperatures (adapted from [166]).

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Particle size of the ground matter and supercritical solvent ow rate are two parameters that can help in understanding where mass transfer is located (as previously discussed). As a rule, the decrease of particle size increases the extraction rate; however, Sabio et al. [167] found a decrease of Lycopene extraction yield at lower particle size and explained (correctly) this effect with in-homogeneities along the extraction bed due to caking (channelling) of the bed when too small particles were used. Of course, Lycopene is not the only compound extracted from tomatoes when a SC-CO2 based solvent is used. -Carotene and large quantities of lipidic compounds are also co-extracted [167]. When compared to organic solvent extraction, the various authors found different maximum relative yields in Lycopene, ranging from 53.9% [169] to about 80% [167] to almost 90% [164] relative yields, the maximum yield being inuenced by the maximum pressure and temperature used. Astaxanthin is a xanthopyll and its extraction has been proposed from various materials as red yeast (Phafa rhodozyma) [64], microalgae (Chlorella vulgaris [138], Haematococcus pluvialis [141]), craysh (crustaceous) [125]. The various authors found that pre-treatments oriented at the decrease of particle size and/or at the destruction of cell walls are relevant in determining the yield and the extraction rate. Particularly, cell walls of microalgae have a polymeric structure that strongly obstacles the extraction of internal compounds [138]. The increase of pressure is also relevant in the extraction efciency: operation at pressures larger than 200 bar shows a marked increase of extraction rate and yield. Pressures up to 500 bar have been tested, and the maximum yield was identied at this pressure value. The effect of temperature is relatively less relevant and temperature higher than 5060 C are also not indicated to avoid extract degradation. Ethanol has been used as co-solvent: it is the only one allowed organic solvent for nutraceutical and pharmaceutical purposes. Valderrama et al. [141], using pressures up to 300 bar, found a strong inuence of ethanol addition (up to 9.4%) on Astaxanthin extraction. The authors that operated up to 500 bar found, instead, only a marked inuence of the cosolvent (percentages up to 15 vol.%) on the extraction rate [64], since the solubility of Astaxanthin in SC-CO2 is larger at higher pressures and compensates the absence of co-solvent. Supercritical solvent ow rate showed only a slight inuence on the extraction yield. Considering the results in the overall, it is conrmed that these processes are conditioned by the internal mass transfer, as suggested by the strong effect of grinding and of the other pre-treatments and by the negligible inuence of supercritical solvent ow rate. The relatively low solubility of Astaxanthin in SC-CO2 also plays a relevant role: high extraction pressures are required to obtain a good extraction performance and the addition of a polar co-solvent increases the extraction rate, since it increases the solubility of Astaxanthin in the solvent mixture. Some authors reported a good Astaxanthin extraction yield, when compared to its initial content in the matrix (up to 97%) [141]; however, the problem of the very large quantity of lipidic

compounds co-extracted has not to be underestimated: overall extraction yields up to 30% (w/w) of the raw material loaded in the extractor can be obtained, for example, in the case of yeasts. Therefore, it is worth of note the indication given by Lim et al. [64] that fractional extraction, performed at two consecutive extraction steps at 300 and 500 bar, can increase the Astaxanthin concentration in the extracts in the second step up to 10 times; indeed, most of the undesired compounds have been extracted during the rst extraction step performed at lower pressure, at which Astaxanthin has very low solubility in the supercritical solvent. 2.3.2. Pharmaceuticals: Hyperforin St. Johns wort (Hypericum perforatum) extracts have well known antidepressant properties. Despite the evident clinical effects, there is still a controversy regarding the active principle of the extracts. Some authors attribute the antidepressant activity to Hypericin and its derivatives, whereas, some studies support the effect of Hyperforin. However, Hypericin is not extracted by SC-CO2 , even when ethanol is used as co-solvent [62]. Rompp et al. [162] tested the extraction of Hyperforin by SC-CO2 from plant particles in the pressure range 90160 bar at 40 and 50 C, varying CO2 ow rate and operating at various extraction times. They substantially found that an increase of the extraction pressure leads to a decrease of Hyperforin concentration in the products, due to an increase of undesired compounds co-extraction. Moreover, the variation of solvent ow rate showed no signicant effect on the extraction yield and Hyperforin content, thus conrming that internal mass transfer controls the extraction process. Catchpole et al. [62] performed this extraction using liquid CO2 , SC-CO2 and SC-CO2 plus ethanol as co-solvent (up to 10 mass%). Using SC-CO2 plus ethanol they obtained an increase of the total yield with respect to the case of SC-CO2 alone (at the same extraction conditions: 300 bar, 40 C) but only a slight increase of Hyperforin extraction was observed. The comparison of the rst separator St. Johns Wort oil yield in the case of SC-CO2 and liquid CO2 is reported in Fig. 2. About the possibility to extract Hypericin, it should be possible (in principle) to extract this drug using a liquid solvent on the vegetable matter and, then, to process the obtained solution by antisolvent extraction. In this case, the liquid solvent is extracted and insoluble Hypericin is precipitated (see for further details in the chapter on supercritical antisolvent extraction). 2.3.3. Pesticides: Pyrethrins and Azadirachtins Pesticides of biological origin are very effective, non-toxic for warm blood animals and have very short degradation times in the presence of air and light. An example of plant containing biopesticides is pyrethrum that has a strong action against insects and is highly biodegradable. Pyrethrins are the six insecticide components that form the biopesticide: they are readily soluble in SC-CO2 even at near critical conditions. Therefore, it is possible to extract these compounds operating, for example, at 90 bar, 40 C [153]. Higher pressures are not required, since they induce the co-extraction of undesidered compounds. This concept is evident in Fig. 3 where it is reported the overall and

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Fig. 2. St. Johns Wort oil yield as a function of CO2 ow rate at two different extraction conditions (adapted from [62]).

Pyrethrins only extraction yield. When a second extraction step at 200 bar and 40 C is performed, the yield of Pyrethrins has no further increase and only undesired compounds are extracted. The fractional separation of the extracts to eliminate co-extracted waxes is, however, required; i.e., the process is very similar to that previously described for essential oils isolation. To eliminate this problem, Kiriamiti et al. [34] proposed a SC-CO2 washing of ungrounded pyrethrum owers to preliminary extract part of cuticular waxes. A variation of this process has been proposed by Kiriamiti et al. [33] that used as the starting material dried crude hexane extract of pyrethrum owers that was loaded in the extractor mixed with 1 mm glass beads. They obtained the coverage of

the beads with a lm of this material. This process is very similar to the extraction of volatile oils from ower concretes [11,16,18]. It allows to work with more concentrated samples and at controlled conditions inside the extractor. Process conditions are similar to those adopted for the extraction from ground owers. Neem seeds possess a well-known pesticide activity due to the presence of various active principles collectively called Azadirachtins that are tetranortriterpenoids formed by a group of closely related isomers such as Salannin, Gemudin and Nimbin. Nimbin has also several valuable medicinal properties [144]. The extraction of these principles using SC-CO2 has been studied by various authors [144147]. The rst step is, of course, seeds grinding and pressing to extract the seed oil. Oil yields between 25 and 30% (w/w) of the starting material have been reported. In this step, small quantities of Azadirachtins are also extracted. The second step is SFE that can be performed at 250300 bar and 4050 C. The SFE product can contain up to 10,000 ppm of Azadirachtins. This process has also been proposed on the industrial scale by Essences srl, Salerno, Italy. Tonthubthimthong et al. [144] concentrated their attention to Nimbin extraction. Concentration of Nimbin in the extracted oil was measured by selectively extracting this compound using methanol. Some experiments of active principles extraction have also been performed adding methanol to SC-CO2 [145,147] in the attempt to obtain more solvent power towards Azadirachtins. According to Johnson and Morgan [147], 20% methanol is very effective in this extraction and reduced pressures with respect to SC-CO2 alone can be used (137 bar). However, Tonthubthimthong et al. [141] found that methanol is not an effective modier for the selective Nimbin extraction. 2.4. Mathematical modelling Mathematical modelling allows a rational approach to the extraction problem, giving the opportunity to generalize the experimental results, and, if successful, to obtain indications about systems different from those studied (simulation). Moreover, it is useful in the development of scaling-up procedures from laboratory to pilot and industrial scales. For these reasons several attempts at mathematical modelling of SFE have been presented in the literature [2,171,172]. A model should not be a mere mathematical instrument, but should reect the physical insight arising from the knowledge of the solid structure and from experimental observations. Mathematical models, which have no physical correspondence to the materials and the process studied are of limited validity, although they can be used to t some experimental data. Three different approaches have been proposed for the mathematical modelling of SFE: (1) empirical [173,174], (2) based on heat and mass transfer analogy [175,176], and (3) differential mass balances integration [171,177,178]. The most proper analysis is obtained from the integration of the differential mass balances: time dependent concentration proles are obtained for uid and solid phase. The extraction curve is calculated from the uid phase concentration at the

Fig. 3. Overall extraction yield (squares) and Pyrethrins yield (circles) against the extraction time during a multistep extraction (adapted from [153]).

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the grinding process. Their shape can inuence the diffusion of the supercritical solvent [35,171]. From the point of view of the extraction mechanisms, other considerations 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: external or internal (and in this case, various possibilities have to be considered). To take into account mass transfer resistances, differential mass balances are applied. Up to now, mathematical modelling has been mainly applied to the extraction of seed oils, essential oils or volatile compounds and to the adsorption/desorption of terpenic model mixtures [181183], since more data exists in the literature for these processes. Materials for which mathematical modelling of SFE has been attempted are reported in Table 3. We have also indicated if the model is based on empirical kinetic equations, on the analogy between heat and mass transfer (HMT) or on differential mass balances integration (DMBI) along the extraction bed or on a single particle. Reverchon et al. [179,184,190,192] used scanning electron microscope to observe broken cells on seed particles surface. They assumed that broken cells form a single layer, and were able to calculate volumetric broken-to-intact cell ratio and thus to reduce the number of model parameters to be evaluated from extraction curves. The concept of broken and intact cells was combined with equilibrium relationship for either free solute [205,206] or solute interacting with matrix [177,180]. Both types of equilibrium were also assumed to occur simultaneously by various authors, the free solute in broken cells and the interacting solute in intact cells [179,180,184,190,192]. In one of these papers [179], an extensive analysis was performed for six seed oils extraction using data from literature. The model was rst validated and then used to simulate several possible cases of extraction. Sovov [172] proposed a general model approach applied to a seed oil and essential oil extraction. The model is based on the division of the process in two extraction periods: the rst one governed by phase equilibrium and the second one by internal diffusion in particles, taking into account the concept of broken and intact cells to explain the sudden reduction of the extraction rate after the rst extraction step. This effect is particularly evident in the case of seed oil extraction. The new feature of the model is the description of the rst extraction period considering different types of phase equilibria: independent on matrix (solubility equilibrium), adsorbed on the matrix (partition between the two phases) and different ow patterns, mainly dispersion. The model has been veried on data sets from literature, related to seeds (almond) and essential oils (orange peels, pennyroyal). This model presents a limit in the case of essential oils extraction, when the extractable material is located only inside the matrix: the concept of broken (in the surface) and intact cells

Fig. 4. SEM image of a section of sunower seed.

extractor outlet.In facing mathematical modelling of SFE, several general aspects have to be taken into account: (a) Solid material structure The knowledge of the botanical aspects and/or optical microscope or scanning electron microscope (SEM) analysis of the material are necessary to visualize its structure. For example, seeds are essentially formed by specialized structures that operate as small recipient containing the oil. Their shape and structure change seed by seed; but the general organization is always the same. An example of seed structure observed by SEM is reported in Fig. 4 and evidences the typical oil bearing structures in the case of sunower seed [35,179]. (b) Location of the compounds to be extracted The distribution of the solute within the solid substrate may be very different. The extractable substances may be free on the surface of the solid material or inside the structure of the material itself. For example, essential oil can be located near the leaf surface in glandular trichomes and/or into vacuoles; i.e., intracellular structures located well inside the leaf [35,180]. (c) Interactions of solutes with the solid matrix Depending on the interactions between the compounds and the solid structure, different equilibria may be involved. Indeed, if the material has no interactions with matrix, equilibrium solubility has to be taken into account. The material can be adsorbed on the outer surface or inside the solid structure. In this case, a partitioning equilibrium between solid and uid phase will occur. (d) Broken-intact cell structures Part of the compounds to be extracted may be near the surface of the structure, due to cell breaking during grinding. This case is characteristic of grinded seed particles: a non-negligible part of the oil is free on particles surface. Moreover, membranes modications may occur due to drying, freeing part of the soluble material. (e) Shape of particles Particles may be spherical, plate-like, etc. as a result of the original shape of the material (for example, leaves) and of

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Table 3 Mathematical modelling of SFE from natural matter Raw material Almond seeds Atlantlic mackerel Basil leaves Blackcurrant seeds Caraway seeds Clove bud Coriander seeds Cupuacu seeds Fennel seeds Ginger rhizomes Grape seeds Hiprose seeds Jalapeno pepper akes Lavender ower Marigold Marjoram Neem seeds Olive husk Orange ower concrete Oregano bracts Palm oil Parsley seeds Peanut Pennyroyal Pepper, black Plane tree leaves Rosemary leaves Soybean lecithin mixture Sunower seeds Tomato seeds Extract Seed oil Fish oil Essential oil Seed oil Essential oil Essential oil Seed oil Fat components Essential oil Oleoresin Seed oil Seed oil Oleoresin Essential oil Oleoresin Essential oil Nimbin Husk oil Volatile oil Essential oil Carotene and lipids Seed oil Seed oil Essential oil Essential oil Mannitol Essential oil Phosphatidylcholine Seed oil Seed oil Type of model DMBI HMT (single sphere model) DMBI DMBI DMBI DMBI DMBI DMBI DMBI DMBI DMBI DMBI DMBI DMBI (shrinking-core) Various models proposed DMBI Empirical models Various models proposed DMBI HMT (single plate model) DMBI DMBI DMBI DMBI DMBI DMBI DMBI DMBI (shrinking-core) DMBI DMBI References [179,184] [185] [186] [187] [186] [188] [179] [189] [179,190] [191] [179,187] [192] [193] [194] [195] [186] [145] [196] [197] [35] [198] [199] [179] [180] [200] [201] [186] [202] [179,203,204] [179]

(inside the particle) is no more applicable and the rst part of extraction controlled by equilibrium does not apply. Gaspar et al. [35] modelled the extraction of oregano essential oil. The model is based on the prevalent geometry of particles: those obtained from leaves tend to maintain a plate-like geometry. Mass balances on the particle have been proposed. Mathematical modelling of SFE has also been proposed for some other materials. Wu and Hou [207], for example, proposed the extraction of egg yolk oil (cholesterol, glycerides and moisture) from egg yolk powder with the scope of producing a matrix (solid residue) rich in phospholipids and proteins. Optimum extraction conditions were found at 55 C and in the pressure range between 280 and 360 bar. They applied differential mass balances integration to the egg powder xed bed. Adsorptiondesorption processes can also be treated as extraction processes: adsorptiondesorption isotherms being the equilibrium curves due to interactions of the solutes between the solid matrix and the uid phase. Differential mass balances also in this case can describe the extraction process. This approach has been used by Reverchon [182] to model the selective desorption from silica gel of two key compounds of essential oils: limonene (representative of the hydrocarbon terpenes fraction) and linalool (representative of the oxygenated terpenes fraction). Then, the model has been extended to the

fractional desorption of bergamot peel oil [181] describing a two steps desorption process with the rst step performed at 40 C, 75 bar to desorb hydrocarbon terpenes and the second step at 40 C, 200 bar to desorb the oxygenated compounds. Later, Reverchon et al. [183] also modelled the selective adsorption on silica gel of a complex terpenic mixture formed by 13 components. The mixture was divided in four families considered as four pseudo-key components. The integration of differential mass balances gave account of the competition among the different compounds for the occupation of the adsorption sites and of displacement effects observed at the exit of the adsorption bed. Flowers concrete is obtained from the dried hexane extract of fresh owers. It is formed by essential oil, colouring matter and large quantities of cuticular waxes. A fractional extraction process has been proposed in which the ower concrete is melted and mixed with glass beads, obtaining an inert core (glass) that supports a given layer of concrete. This process has been used successfully for the fractionation of several ower concretes [11,16,18]. Mathematical modelling has been performed [197,208]. The volatile oil has been considered to be a mixture of four compound families (pseudo-components) extracted from an active layer of concrete on a spherical inert core. Modelling of oxygenated terpenes and oxygenated sesquiterpenes extraction was obtained.

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3. Liquid feed processing The fractionation of liquid mixtures in two or more fractions is another relevant process. In a typical apparatus, two pumps deliver the liquid solution and SC-CO2 to the packed column. The packing is an inert material characterized by a large specic surface whose scope is to favour the contact between the liquid and the supercritical uid. SC-CO2 as a rule ows along the column from the bottom to the top, whereas, the liquid solution is usually added to the top. However, it is also possible to feed the liquid at an intermediate position along the column and to add a recycle of part of the uid phase exiting at the top. 3.1. Selection of the operating parameters The process is based on the different solubilities of the liquids to be separated in SC-CO2 . The ideal case is obtained when only the compounds to be extracted are soluble in SC-CO2 , whereas, all the other liquid components are completely insoluble. However, this case is rare and a limited solubility of the other liquid compounds forming the mixture has to be taken into account. For this reason, pressure and temperature of the process have to be accurately chosen to select the conditions at which there is the maximum difference in solubility among the compounds to be extracted and all the other compounds in the mixture. Also in this case, CO2 density is frequently used as a criterion to nd the conditions of maximum selectivity. The difference in density between the liquid and SC-CO2 is another parameter to be taken into account: to allow the countercurrent operation, SCF density has to be lower than the one of the liquid mixture. The traditional operation of packed columns requires that liquid ow rate will be larger than the minimum amount that assures the complete wetting of the packing. The feed ratio is also selected to avoid the massive entrainment of the liquid in the uid phase (ooding). These conditions have to be respected also when a supercritical uid is used as the uid-processing medium. The classical calculation in terms of the number of

theoretical equilibrium stages required for separation can also be applied. A possible variation of this processing scheme can consist of the adoption of a temperature prole along the column with the aim of optimising the separation temperature with respect to the composition of the mixtures at different levels inside the column. The extraction of liquid mixtures is controlled by the relative solubilities in SC-CO2 of the various compounds forming the mixture that is the thermodynamic limitation of the process. Mass transfer between the two phases represents the kinetic limitation. The distance from the equilibrium condition is the driving force for the separation along the column. 3.2. Examples of application The fractionation of liquid mixtures by SFE has been proposed for various applications, as it can be seen in Table 4. Two examples will be treated in details in the following: hexane elimination from vegetable oils that represent a new approach to seed oils extraction and fried oil fractionation to recover reusable compounds. 3.2.1. Hexane elimination from seed oils This process represents a different approach to the supercritical extraction of seed oils. Indeed the supercritical extraction applied directly to seeds suffers the disadvantage of high costs due to the use of large pressurised vessels and to the intrinsic discontinuous operation. If the approach is to treat the liquid hexane oil mixture after the traditional hexane extraction (composition 70% hexane30% oil), it is possible to use smaller apparatuses and a continuous operation that allows the processing of large quantities of the raw mixture. Hexane and triglycerides are both soluble in SC-CO2 , but at a temperature of 40 C, hexane is completely miscible for pressures larger than about 100 bar, whereas, at the same temperature, triglycerides show a non-negligible solubility in SC-CO2 only for pressures larger than about 250 bar. Therefore, these compounds can be separated, operating in a packed tower at low pressures (<200 bar).

Table 4 Fractionation of liquid mixtures by SFE in continuous (C) and semicontinuous (SC) plants Initial mixture Acetic acid + water Alcoholic drink Citrus peel oil key mixture Citrus oil Edible oil model mixtures Fish oil Fried oil Glyceride mixtures Hexane + soybean oil Olive leaves + hexane Olive oil Olive oil Origanum oil Orange juice Shark liver oil Material to be recovered Acetic acid Brandy aroma Limonene and linalool Limonene Squalene Vitamin A palmitate Triglycerides Lipids Soybean oil Squalene, -carotene, tocopherol Squalene Squalene, tocopherols Deterpenation Antioxidants Squalene Process C C C C C C C SC C C C C SC C C References [209] [210,211] [212] [213] [214,215] [216,217] [218] [219] [220] [221] [222] [223] [224] [225,226] [222,227]

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Using these concepts, the fractionation of soybean oilhexane mixtures has been successfully performed using a 1.8 m tall packed tower, charged with stainless steel perforated saddles with a very large specic surface. The extraction has been performed at 120 bar, 40 C using different starting concentration of soybean oil in hexane. A single passage in the packed tower allowed to obtain a bottom product formed by soybean oil containing down to 20 ppm of hexane residue and to recovery pure hexane at the top of the column [220]. 3.2.2. Fried oil fractionation The fractionation process using SC-CO2 can be used to purify used fried oils. A selective separation of the oil components based on their polarity and molecular weight can be attained, since the degradation compounds are mainly peroxides and polymers of the original tryglicerides mixture. The SC-CO2 purication of peanut oil used for frying has been studied using the continuous fractionation in a packed column. The inuence of pressure (150350 bar) and temperature (2555 C) on the yield and on the composition of top and bottom products was studied. Process conditions were selected to separate triglycerides from degraded compounds and experimental results indicated that the operating conditions leading to maximal triglycerides recovery in the extract were 350 bar, 55 C, and a solvent-tofeed ratio of 53. Operating at these conditions, it was possible to recover 97% of the triglycerides feed to the column and approximately 52 wt.% of the used fried oil. The composition of the puried top stream was very similar to that of fresh fried oil [218]. 3.3. Mathematical modelling Mathematical modelling of counter-current packed column has been studied only by a few authors [228232] and only in some cases with reference to natural matter fractionation [228,231]. The most interesting work is the one proposed by Ruivo et al. [228], which performed the dynamic modelling and simulation of a packed column. They used the experimental data on a model binary mixture formed by squalene and methyl oleate, fractionated using SC-CO2 . The model was formed by a set of partial differential equations that correspond to the differential mass balances on the packed column and algebraic equations that describe the mass transfer, the hydrodynamics of the twophase ow through the packings and the ternary thermodynamic equilibrium for the studied system. The column was considered at constant temperature. A fair good agreement was obtained between measured and predicted composition proles of the outlet streams over the time. 4. Antisolvent extraction The recovery of solid compounds from a liquid mixture requires different process approaches since the xed bed extractor is not adapt to process liquid mixtures and the packed tower cannot be used in these cases since precipitation of the solid compounds will be obtained on the internal packings.

The supercritical antisolvent extraction (SAE) process is conceptually very similar to supercritical antisolvent micronization (SAS); but the scope of the process is the recovery of one or more solid compounds from a liquid mixture. It consists of the continuous ow of SC-CO2 and of the liquid mixture in a pressurized precipitation vessel. If the process conditions have been properly selected, the liquid is rapidly dissolved in the supercritical uid, whereas, the solid precipitates at the bottom of the precipitation vessel. Therefore, in a possible representation of the process two pumps deliver the liquid solution and the supercritical uid, respectively. The precipitation vessel is used to collect the solid and a vessel located downstream the precipitator and operated at lower pressure (for example, 30 bar and 25 C) is used to recover the liquid. 4.1. Selection of the operating parameters The rst step of this process is the formation of a spray of the liquid solution. The scope of this operation is to produce a very large liquid surface due to the formation of small liquid droplets to strongly enhance the rate of solubilization of the liquid phase in the supercritical medium. For the same reason, the process is performed at operating conditions at which the liquid solvent is completely soluble in SC-CO2 . The knowledge of solubility data on the liquid solvents and of the solids in SC-CO2 is mandatory for this process for the proper selection of process temperature and pressure. In the case of SAE, the interactions between thermodynamic constrains and mass transfer mechanisms also control the process performance. The enhanced mass transfer that characterizes SCFs is again a distinctive advantage of their use as extraction media, together with the fast and complete separation by simple depressurisation between the supercritical solvent and the liquid. A limitation of this process is the possible formation of a ternary mixture liquid/solid/SC-CO2 . Indeed, the presence of the liquid can induce an increase of the solubility of the solid compounds in SC-CO2 . In this case, the liquid can act as a cosolvent from the point of view of the solid solubilization. When this phenomenon occurs, the part of solid retained in the uid phase obviously does not precipitate and is lost in the liquid recovered in the separation vessel. The limit case is the complete solubilization of the solid in the uid phase that produces the process failure. 4.2. Examples of application Antisolvent extraction until now has been used in a limited number of processes (see Table 5) but it has a large potential for future applications. Some examples will be described in the details: lecithin extraction from soybean oil, propolis tincture fractionation and tobacco proteins separation. 4.2.1. Lecithin extraction from soybean oil Crude lecithin, in general, contains a minimum of 35 wt.% oil, which needs to be reduced to less than 2 wt.% oil before it can be used as an emulsier. The crude lecithin is convention-

E. Reverchon, I. De Marco / J. of Supercritical Fluids 38 (2006) 146166 Table 5 Supercritical antisolvent extraction Initial mixture Propolis tincture Lecithin + triglyceride oil Essential oil + triglyceride oil Curcuminoid + triglyceride oil Oat bran + acetone Lecithin + hexane Tobacco + ethanol Material to recover Flavonoids Lecithin Essential oil Curcuminoid Triacylglycerols Lecithin Proteins References [233] [234,235] [234,235] [234,235] [236] [237] [238]

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primary product, and an essential oil/ethanol fraction as a secondary product. Operating at 300 bar, almost 100% recovery of avonoids was obtained. The optimum tincture concentration appeared to be about 10 mass%. The concentration of propolis in the tincture is the parameter that has the greatest effect on the yield and concentration of avonoids in the product fraction. The process has been successfully scaled up to a demonstration scale using optimized pressure, temperature, ow ratio and tincture concentrations obtained from laboratory and pilot scale trials. 4.2.3. Proteins extraction from tobacco Cigarette manufacturers have devised systems to reduce the nicotine and tar content of the burning tobacco for health reasons. Most of these systems have resulted in a safer smoking product, but they do not remove all of the undesirable constituents in the tobacco smoke. Proteins in cured tobacco are either precursors of undesired compounds in the smoke either a valuable source of useful compounds. Therefore, the supercritical antisolvent extraction has been used by Scrugli et al. [238] to remove protein compounds from cured tobacco by ethanolic extraction and to recover the proteic compounds from the obtained solution. Alkaloids like nicotine are soluble in SC-CO2 especially at high densities, cuticular waxes and avouring compounds can also been readily extracted. Therefore, a fractionation of the ethanolic extract is possible, if processing conditions are selected to induce proteic compounds precipitation and the transfer in the uid phase of the liquid solvent together with nicotine, waxes and avouring components. The experiments have been performed at different pressures and solid concentrations. The ethanolic extract was efciently fractionated in all the experiments. The chemical analyzes performed on the fractions recovered shown that the yield of precipitated material was about 40% (w/w of extract) in each experiment. Particularly interesting is the total absence of nicotine in the precipitates, whereas, it is totally recovered with avours and pigments, in the ethanolic residues. 4.3. Mathematical modelling No specic papers dedicated to SAE modelling have until now been published. However, due to the similarities of this process with SAS, part of the considerations developed for that process [244248] could be adapted to SAE. Since only precipitation is required in SAE with no specications on particle size, the spray formation/efciency is not particularly relevant even if a large contact surface favours the rate of precipitation. Phase equilibria will play a role even more relevant than in SAS. Indeed, in SAE we are interested in the separation of the solid phase and, as a rule, complex mixtures are processed; therefore, interactions among the compounds present in the mixture are involved and will be very difcult to be predicted. 5. Conclusions and perspectives SFE and liquids fractionation in the period of time considered (1996 to present time) have moved along two major direc-

ally rened for removal of oil by repeated solvent extractions with acetone, as lecithin is acetone insoluble. Removal of oil from crude lecithin by conventional organic solvents has several disadvantages, such as, a large amount of solvent is needed, it is tedious and time-consuming, and a gelatinous lumpy mass is formed at the nal stage, which reduces the mass transfer efciency of the process. Some authors have proposed to apply the SAE to this process since seed oils are soluble in SC-CO2 (though at pressures larger than about 280 bar, as previously specied) and phospholipids are completely insoluble in this medium. Thus, the proposed process consists of operating the antisolvent extraction with SCCO2 at, for example, 400 bar and 40 C with a continuous ow of CO2 and an injection system that sprays in the precipitator the lecithin containing oil in form of small droplets [239241]. The oil solubilized in SC-CO2 is extracted and recovered in a separator operated at low pressure. Lecithin precipitates as a solid powder and is collected time by time when the vessel is discharged. A further evolution of this process has been proposed by Mukhopadhyay and Singh [237]. In this method, crude lecithin is dissolved in hexane and is contacted with dense CO2 . The CO2 dissolution in the solution causes a large partial molar volume reduction of hexane [242,243]. As a result, there is a reduction of its solvent power for lecithin, producing a selective precipitation of lecithin. 4.2.2. Propolis tincture fractionation Propolis contains a high concentration of avonoids, which are used in a wide range of cosmetic and health food preparations for their antimicrobial properties. Propolis is usually dissolved in ethanol or ethanol/water mixtures to remove insoluble material such as waxes. The resultant solution is a propolis tincture. A supercritical antisolvent extraction process has been proposed for the fractionation of propolis tincture [233] to obtain avonoids and essential oil fractions by extraction, and to remove high molecular mass components by antisolvent precipitation. Flavonoids are practically insoluble in pure CO2 , but sufciently soluble in CO2 + ethanol to enable their separation from high molecular mass and/or more polar components. In the rst step of the process, supercritical CO2 is used both as an antisolvent to precipitate high molecular weight components, and as a solvent to extract the ethanol and soluble components of the propolis. This extract is then fractionated in two separation steps to create a concentrated avonoid fraction as the

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E. Reverchon, I. De Marco / J. of Supercritical Fluids 38 (2006) 146166 [15] E. Reverchon, G. Della Porta, R. Taddeo, Extraction of sage essential oil by supercritical CO2 : inuence of some process parameters, J. Supercrit. Fluids 8 (1995) 302309. [16] E. Reverchon, G. Della Porta, Rose concrete fractionation by supercritical CO2 , J. Supercrit. Fluids 9 (1996) 199204. [17] G. Della Porta, S. Porcedda, B. Marongiu, E. Reverchon, Isolation of eucalyptus oil by supercritical uid extraction, Flavour Fragr. J. 14 (1999) 214218. [18] E. Reverchon, G. Della Porta, Tuberose concrete fractionation by supercritical carbon dioxide, J. Agric. Food Chem. 45 (1997) 13561360. [19] G. Della Porta, R. Taddeo, E. DUrso, E. Reverchon, Isolation of clove bud and star anise essential oil by supercritical CO2 extraction, Lebensm.Wiss. U.-Technol. 31 (1998) 454460. [20] A. Caredda, B. Marongiu, S. Porcedda, C. Soro, Supercritical carbon dioxide extraction and characterization of Laurus nobilis essential oil, J. Agric. Food Chem. 50 (2002) 14921496. [21] B. Marongiu, S. Porcedda, G. Della Porta, E. Reverchon, Extraction and isolation of Salvia desoleana and Mentha spicata subsp. insularis essential oils by supercritical CO2 , Flavour Fragr. J. 16 (2001) 384 388. [22] B. Marongiu, S. Porcedda, A. Piras, A. Rosa, M. Deiana, M.A. Dess`, Antioxidant activity of supercritical extract of Melissa ofcinalis subsp. ofcinalis and Melissa ofcinalis subsp. inodora, Phytother. Res. 18 (2004) 789792. [23] B. Simandi, A. Deak, E. Ronyai, G. Yanxiang, T. Veress, E. Lemberkovics, M. Then, A. Sass-Kiss, Z. Vamos-Falusi, Supercritical carbon dioxide extraction and fractionation of fennel oil, J. Agric. Food Chem. 47 (1999) 16351640. [24] B. Simandi, A. Sass-Kiss, B. Czukor, A. Deak, A. Prechl, A. Csordas, J. Sawinsky, Pilot-scale extraction and fractional separation of onion oleoresin using supercritical carbon dioxide, J. Food Engrg. 46 (2000) 183188. [25] E. Vagi, B. Simandi, H.G. Daood, A. Deak, J. Sawinsky, Recovery of pigments from Origanum majorana L. by extraction with supercritical carbon dioxide, J. Agric. Food Chem. 50 (2002) 22972301. [26] M.M. Esquivel, M.A. Ribeiro, M.G. Bernardo-Gil, Supercritical extraction of savory oil: study of antioxidant activity and extract characterization, J. Supercrit. Fluids 14 (1999) 129138. [27] M.A. Ribeiro, M.G. Bernardo-Gil, M.M. Esquivel, Melissa ofcinalis L.: study of antioxidant activity in supercritical residues, J. Supercrit. Fluids 21 (2001) 5160. [28] E. Dauksas, P.R. Venskutonis, B. Sivik, T. Nillson, Effect of fast CO2 pressure changes on the yield of lovage (Levisticum ofcinale Koch.) and celery (Apium graveolens L.) extracts, J. Supercrit. Fluids 22 (2002) 202101. [29] E. Dauksas, P.R. Venskutonis, V. Povilaityte, B. Sivik, Rapid screening of antioxidant activity of sage (Salvia ofcinalis L.) extracts obtained by supercritical carbon dioxide at different extraction conditions, Nahrung/Food 45 (2001) 338341. [30] B.-J. Wang, Y.-H. Lien, Z.-R. Yu, Supercritical uid extractive fractionationstudy of the antioxidant activities of propolis, Food Chem. 86 (2004) 237243. [31] B.-J. Wang, C.-T. Liu, C.-Y. Tseng, C.-P. Wu, Z.-R. Yu, Hepatoprotective and antioxidant effects of Bupleurum kaoi Liu (Chao et Chuang) extract and its fractions fractionated using supercritical CO2 on CCl4 -induced liver damage, Food Chem. Toxicol. 42 (2004) 609617. [32] G. Vasapollo, L. Longo, L. Restio, L. Ciurlia, Innovative supercritical CO2 extraction of Lycopene from tomato in the presence of vegetable oil as co-solvent, J. Supercrit. Fluids 29 (2004) 8796. [33] H.K. Kiriamiti, S. Camy, C. Gourdon, J.-S. Condoret, Supercritical carbon dioxide processing of pyrethrum oleoresin and pale, J. Agric. Food Chem. 51 (2003) 880884. [34] H.K. Kiriamiti, S. Camy, C. Gourdon, J.-S. Condoret, Pyrethrin extraction from pyrethrum owers using carbon dioxide, J. Supercrit. Fluids 26 (2003) 193200. [35] F. Gaspar, T. Lu, R. Santos, B. Al-Duri, Modelling the extraction of essential oils with compressed carbon dioxide, J. Supercrit. Fluids 25 (2003) 247260.

tions: consolidation of the knowledge in previously explored elds (e.g., essential oils, vegetable oils, etc.) and exploration of several high added values compound categories of interest for nutraceutical, cosmetic and pharmaceutical industries. This second approach is scientically challenging but also necessary to nd applications that are industrially competitive with the traditional processes based on cheaper technologies and plants. In some cases, the extraction problems proved to be very complex and as a consequence more evolved process schemes (multistep extraction, continuous solid processing, multistage separations, co-solvents) have been adopted to overcome these problems. However, a large quantity of work is still required, particularly, in the liquid fractionation process that has been used only in a limited quantity of applications, but, has a large potential. Supercritical antisolvent extraction represents a case apart since it has large possibilities of application; but it has been explored only in a very few cases. Mathematical modelling has also been proposed in some cases, but this activity is far to be complete, considered the large quantity of possible structures, interactions, etc. The development of industrial applications of SFE processes is in progress, especially in the eld of nutraceuticals products that are followed with attention by various companies. Liquid fractionation and supercritical antisolvent extraction have until now tested only up to the pilot scale. References
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