Solubility of the Natural Antioxidant Gallic Acid in Supercritical CO 2 + Ethanol as a Cosolvent Amparo Cha ´ fer,* ,² Tiziana Fornari, ‡ Roumiana P. Stateva, § Angel Berna, ² and Jose ´ Garcı ´a-Reverter | Departamento de Ingenierı ´a Quı ´mica, Universidad de Valencia, 46100 Burjassot, Spain, A Ä rea de Tecnologı ´a de Alimentos, Universidad Auto ´noma de Madrid, Madrid, Spain, Institute of Chemical Engineering, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria, and Agrofood Technology Institute (ainia), Apdo 103, Parque Tecnolo ´gico de Vale `ncia, 46890 Paterna, Spain Solubility data of solid 3,4,5-trihydroxybenzoic acid (gallic acid) in supercritical CO 2 + ethanol as a cosolvent are reported in this work. Measurements were carried out in the temperature range (313.15 to 333.15) K, pressures ranging from (10 to 40) MPa, and different ethanol modifier content ranging from (0.7 to 6) %. The experimental data were correlated using the Soave-Redlich-Kwong equation of state and the group contribution associating equation of state. The thermodynamic modeling analysis includes also the solubility representation of an important class of natural antioxidants (e.g., gallic acid esters) in supercritical CO 2 . Introduction Plant foods and products are rich sources of a variety of biologically active compounds, and these phytochemicals have been found to possess hypolipidemic, antiplatelet, antitumor, antioxidant, and immune-stimulating properties. 1 In recent years, particular attention has been given to a specific class of antioxidant phytochemicals, the polyphenols, which are com- prised basically of phenolic acids, including benzoate and hydroxycinnamate derivates, and flavonoids. 3,4,5-Trihydroxybenzoic acid (gallic acid) and its derivatives are polyphenyl natural products, which are found to be particularly abundant in processed beverages such as red wines and green teas. 2,3 They have radical scavenging, anti-oxidative, 4-7 anti-inflammatory, 8,9 anti-fungal, 10 anti-cancer, 11 and chemo- protective 12 properties, which are of great importance for the food, pharmaceutical, and drug industries. This explains the interest and motivation to isolate these compounds from natural vegetable matrices, applying an environmentally safe and efficient “green” processssuch as supercritical fluid extraction (SFE)sas a viable alternative to the wet extraction. The design of SFE processes requires knowledge of the solute solubility in the supercritical phase and the ability to efficiently model and predict it. Gallic acid has been extracted using CO 2 + cosolvent (methanol) from grape seeds 13-15 and from a spiked solid. 16 Recently, Murga et al. 17 reported the solubility of gallic acid methyl ester (methyl gallate) in pure supercritical carbon dioxide (SCCO 2 ). Solubility data for n-propyl 3,4,5-trihydroxy- benzoate (propyl gallate) and dodecyl-3,4,5-trihydroxybenzoate (lauryl gallate; dodecyl gallate) in SCCO 2 were obtained by Cortesi et al., 18 but no data on gallic acid were reported since for the latter the solubility in pure SCCO 2 was very low (less than 10 -6 in molar fraction) and was close to the experimental error. 18 The present paper provides for the first time experimental data on the solubility of solid gallic acid in SCCO 2 + ethanol as a cosolvent. Ethanol was used as a modifier in order to increase gallic acid solubility in the supercritical phase and was chosen because it is a polar solvent, its use is allowed in the food industry, and it can be easily removed from the extract by evaporation at relatively low temperature. Two different thermodynamic models were applied to cal- culate the solubility data for gallic acidsthe Soave-Redlich- Kwong equation of state (SRK-EoS) and a modification of the group contribution associating equation of state (GCA-EoS) presented recently. 19 The capabilities of the latter model were tested also by correlating the solubility of three gallic esters in SCCO 2 smethyl 2,4,6-trihydroxybenzoate (methyl gallate), pro- pyl and dodecyl gallate, respectively. In addition, the paper presents estimated values for the thermophysical properties and sublimation pressures of gallic acid and the three gallic acid esters. The values obtained are compared with those reported in the literature by other authors and calculated by different methods. Experimental Section Chemicals. Gallic acid (g 98 mass %, HPLC grade) was purchased from Aldrich Chemical Co. Inc. Absolute ethanol (99.8 mass %, GC grade), supplied by Prolabo S.A., was used as a modifier and solvent to collect the extract. The reagents were used without further purification since chromatography did not show any significant impurities. High-purity CO 2 (more than 99.9 vol % purity, SFC grade) supplied by AIR LIQUIDE was used as received. Silica (more than 99.8 mass %) extra pure (from Sigma Chemical Co. Inc.) was utilized as a support of the products. Equipment and Procedure. The solubilities were measured with an SFX 3560 extractor with two syringe pumps (model 260D) manufactured by ISCO (Lincoln, NE). With the proper plumbing, a two-pump system can deliver modified supercritical fluid or a continuous flow of supercritical fluid. The cylinder capacity of the pump is 266 mL, and the maximum pressure is 51 MPa. The temperature can range from (313.2 to 423.2) K, and supercritical fluid flow rate can range from (0.5 to 5) mL·min -1 . A further detailed description of the equipment can be found in a previous work 20 and will not be given here. * Corresponding author. Fax: +34-963544898. Phone: +34-963543434. E-mail: Amparo.Chafer@uv.es. ² Universidad de Valencia. ‡ Universidad Auto ´noma de Madrid. § Bulgarian Academy of Sciences. | Parque Tecnolo ´gico de Vale `ncia. 116 J. Chem. Eng. Data 2007, 52, 116-121 10.1021/je060273v CCC: $37.00 © 2007 American Chemical Society Published on Web 11/01/2006