Solubility of Glycyrrhizin in Supercritical Carbon ... - ACS Publications

May 18, 2015 - because it has functions of antiulcer,14 antivirus15 and inhibitory action on HIV .... no monotony variation trend of the glycyrrhizin ...
0 downloads 0 Views 872KB Size
Article pubs.acs.org/jced

Solubility of Glycyrrhizin in Supercritical Carbon Dioxide with and without Cosolvent Jing-fu Jia, Fatemeh Zabihi, Ya-hui Gao, and Ya-ping Zhao* School of Chemistry & Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China S Supporting Information *

ABSTRACT: The solubility of glycyrrhizin in supercritical carbon dioxide (SCCO2) with cosolvent ethanol at the mole fraction of (0, 0.02, and 0.04) was measured, respectively, at pressures of (9 to 21) MPa and temperatures of (308, 318, and 328) K. The results revealed that the glycyrrhizin solubility depended on the pressure, temperature, and cosolvent mole fraction. The glycyrrhizin solubility in pure SCCO2 was well correlated with Chrastil, Bartle, and Mendez-Santiago and Teja models with the average absolute relative deviation (AARD) below 6.82 %. The glycyrrhizin solubility in SCCO2 with cosolvent was correlated by Chrastil modified by González (Chrastil-G), and MST modified by Sauseau (MST-S) models with satisfactory AARD below 3.85 %. The results provide fundamental data in designing extraction of glycyrrhizin from the licorice or preparation of its particle using SCCO2 techniques.



INTRODUCTION Supercritical carbon dioxide (SCCO2) techniques has been widely studied in many fields such as pharmaceuticals, food nutrients, and industrial materials during the past few decades1−3 because of its nontoxicity, economy, and mild operating conditions. For the application of SCCO2 in the extraction, the reaction, the particle formation, the encapsulation, etc.,4−6 solute solubility in SCCO2 at pressures and temperatures are very crucial for the operation design or election parameter. A great number of solubility data of substances in SCCO2 have been measured.7−10 However, there has been only a few studies on the solubility of glycosides reported,11,12 and no solubility data of glycyrrhizin has been measured yet. Glycyrrhizin, one of the main active components of the licorice root,13 is widely used in the pharmaceutical field because it has functions of antiulcer,14 antivirus15 and inhibitory action on HIV replication.16 It is also applied in the food industry as a sweetener17 and flavoring agent.18 Extraction of glycyrrhizin using SCCO219 has a lot of advantages, such as no remains of toxic solvents, lower extraction temperature, and shorter extraction time. Furthermore, SCCO2 can also be utilized to produce glycyrrhizin nanoparticles or glycyrrhizinloaded polymer particles that may improve the bioavailability of glycyrrhizin,20 in which the rapid expansion of supercritical solution (RESS) and the supercritical antisolvent method (SAS) were often utilized.21,22 The solubility of glycyrrhizin in SCCO2 is important for all these processes. The purpose of this study is to provide fundamental data for the extraction and particle preparation process of glycyrrhizin using the supercritical CO2 technology, and to find a way of predicting the solubility of glycyrrhizin in SCCO2. In this work, © 2015 American Chemical Society

the equilibrium solubility of glycyrrhizin in SCCO2 was measured at temperatures of (308, 318, and 328) K and pressures of (9 to 21) MPa. The influence of ethanol as a cosolvent on the solubility was also investigated. The glycyrrhizin solubility in both pure SCCO2 and SCCO2 with cosolvent were correlated with five density-based semi-empirical models, respectively.



EXPERIMENTAL METHODS Materials. Glycyrrhizin and salicylic acid were purchased from Sinopharm Chemical Reagent Co., Ltd., and their structures are shown in Figure 1. CO2 was supplied by SJTU chemical store (Shanghai, China). Ethanol (EtOH) was purchased from Shanghai Lingfeng Chemical Reagent Co., Ltd. (Shanghai, China). The compound descriptions are listed in Table 1, and all the materials were used without further purification. Apparatus and Procedure. The schematic diagram of a homemade dynamic apparatus used to measure the solubility of glycyrrhizin in SCCO2 is shown in Figure 2. The certain amount of glycyrrhizin powder was preloaded in the sample vessel and the procedure of solubility measurement is as follows: at the beginning, CO2 was delivered using a high pressure injecting pump into the system. The air in the system was replaced with CO2 for several times to eliminate the air as completely as possible by adjusting the pressure relief valve VR. Meanwhile, the system was heated and kept the desired temperature by a controlled thermostat. After the desired Received: December 14, 2014 Accepted: May 7, 2015 Published: May 18, 2015 1744

DOI: 10.1021/je5011328 J. Chem. Eng. Data 2015, 60, 1744−1749

Journal of Chemical & Engineering Data

Article

Figure 1. Chemical structural formula of glycyrrhizin and salicylic acid.

Table 1. Chemical Structure and Purity of Glycyrrhizin compound

formula

source

molecular weight (g/mol)

CAS

mass fraction purity

glycyrrhizin salicylic acid CO2 ethanol

C42H62O16 C7H6O3 CO2 C2H6O

Sinopharm Sinopharm SJTU Lingfeng

822.94 138.12 44.01 46.07

1405−86−3 69−72−7 124−38−9 64−17−5

99.1 % 99.6 % 99.99 % 99.5 %

50 mL volumetric flask as stock solution from the beaker. All experiments were performed in triplicate. The procedure of measuring the glycyrrhizin solubility in SCCO2 with cosolvent was similar, except that at the beginning, a calculated amount of ethanol was injected into the system in advance. Analytical Method. The sample taken from the stock solution corresponding to each experiment was diluted by 10 times before analyzing using an ultraviolet spectrophotometry detector (UV, 765PC, Shanghai Spectrum Instruments, Shanghai, China) at 248 nm. The calibration curve was determined by a group of standard samples with a regression coefficient of more than 0.9999. Each point was measured at least three times and their average value was adopted. The glycyrrhizin solubility in SCCO2 with or without cosolvent was defined as the mole ratio of glycyrrhizin to CO2 in the U-sample collector. The mole amount of CO2 was calculated based on the inner volume of U-sample collector and the density of CO2 corresponding to the operating conditions, which was obtained from the National Institute of Standards and Technology (NIST) fluid property database. The uncertainties of the solubility data in pure SCCO2 and SCCO2 with cosolvent were determined to be (1.88 and 1.30) %, separately. Many semi-empirical models were used to predict the solubility behavior.23 Because many physical values of glycyrrhizin, like the sublimation pressure, are not available, several densitybased models that only require several known parameters (temperature, pressure, CO2 density, cosolvent mole fraction, etc.) were chosen in this work. Chrastil,24 Bartle,25 and Mendez-Santiago and Teja (MST)26 models were elected to correlate the solubility in pure SCCO2, while Chrastil modified by González (Chrastil-G)27 and MST modified by Sauseau (MST-S)28 models were employed to correlate the data with cosolvent. The detailed descriptions of these models are shown in Table 2.

Figure 2. Experimental apparatus for solubility measurement (T = 308 K).

conditions were achieved, the valves VR and V1 were closed. The SCCO2 was started to circulate in the system by the circulating pump. According to pre-experimental results, the circulating time was set for 2 h. When the system becomes equilibrium, the valves V2 and VC at the inlet and outlet of the 50 mL U-sample collector were closed, and the certain amount of SCCO2 with dissolved solute was sealed inside. The amount of SCCO2 can be calculated using the CO2 density corresponding to the operating conditions and the inner volume of the collector. Finally, the U-sample collector taken down was cooled and depressurized by releasing the CO2 into a 100 mL beaker containing 20 mL of ethanol very slowly, making the dissolved glycyrrhizin precipitated inside the U-sample collector, which was then washed by ethanol for more than three times, and the washing solvent was combined with the solution of the beaker. Then, the obtained solution was transferred to a 1745

DOI: 10.1021/je5011328 J. Chem. Eng. Data 2015, 60, 1744−1749

Journal of Chemical & Engineering Data

Article

Table 2. Correlation Parameters for the Solubility of Glycyrrhizin in SCCO2 with and without Cosolvent and AARD of Different Models correlation parameters equationa

cosolvent mole fraction

a0

a1

a2

Chrastil

a ln y = a0 + a1 ln ρ + 2 T

without

13.17

1.12

−6.10 × 103

4.23 %

Bartleb

⎛ yP ⎞ a ln⎜ ⎟ = a0 + a1(ρ − ρC ) + 2 T ⎝ PC ⎠

without

27.16

0.004

−8.31 × 103

6.78 %

MST

T ln(yP) = a0 + a1ρ + a 2T

without

−9.26 × 103

1.30

30.20

6.82 %

Chrastil-G

a ln y = a0 + a1 ln ρ + 2 + a3 ln yc T

0.02 and 0.04

16.49

1.93

−7.00 × 10

1.23

3.38 %

MST-S

⎛ yP ⎞ T ln⎜ ⎟ = a0 + a1ρ + a 2T + a3yc ⎝ P0 ⎠

0.02 and 0.04

−1.14 × 104

1.88

35.69

1.37 × 104

3.85 %

name

a3

3

AARD

a In this work, values of solubility y are substituted by y·106 for convenient operation, without influence on model testing. bPC and ρC are the critical pressure and density of CO2. yc is the mole fraction of cosolvent. P0 is the standard atmospheric pressure.

Table 3. Solubility (y) of Glycyrrhizin in Pure SCCO2 at Temperatures of (308, 318, and 328) K and Pressures from (9 to 21) MPa Ta/K

P/MPa

ρb/g·L−1

y·106

308

9 12 15 18 21 9 12 15 18 21 9 12 15 18 21

662.13 767.07 815.06 848.04 873.67 337.51 657.74 741.97 789.24 822.91 255.54 504.51 653.50 723.08 767.88

1.54 2.06 2.17 2.49 2.98 2.27 3.20 3.85 4.75 5.72 2.05 3.85 5.37 6.95 8.61

318

328

Figure 3. Comparison of solubility data of salicylic acid in supercritical carbon dioxide.



a

Standard uncertainties u are the following: u(T) = 0.1 K, u(P) = 0.2 MPa, u(y) = 1.88 %. bρ is the density of pure CO2 obtained from the National Institute of Standards and Technology (NIST) fluid property database.

RESULTS AND DISCUSSION Glycyrrhizin Solubility in SCCO2. To start with, the reliability of the equipment and the procedures were verified by measuring the solubility of salicylic acid in SCCO2 and then comparing with literature data.29−31 The results are shown in Figure 3, where satisfactory agreement between various measurements can be observed. The numerical data for the solubility of salicylic acid in SCCO2 are given in Table 1S (Supporting Information). The experimental conditions and results made in pure SCCO2 are listed in Table 3. It can be seen from Table 3 that the glycyrrhizin solubility changes with different conditions. As shown in Figure 4, glycyrrhizin solubility increases with increasing pressure at the temperatures investigated. This can be attributed to the enhanced solvent power of SCCO2 when the density of SCCO2 increased with pressure increases. An isobaric solubility increase with temperature is also found at pressures examined, except 9 MPa. These results indicate two adverse effects of temperature on the solubility, which have been reported in a previous paper.32 As the temperature increases, the density of SCCO2 decreases, leading to the decrease of the solvent power, but the vapor pressure of glycyrrhizin increases, giving positive effect on the solubility.

At 9 MPa, these two effects have intense competition, causing no monotony variation trend of the glycyrrhizin solubility. However, at higher pressure, the glycyrrhizin vapor pressure might dominate its solubility. The solubility of glycyrrhizin (y) within the experimental conditions changes from 1.54 × 10−6 to 8.61 × 10−6, and this low solubility is because glycyrrhizin, having three carboxylic groups, is a polar molecule. Similarly, influence of ethanol on the solubility of glycyrrhizin in SCCO2 was investigated. Ethanol mole fraction was 0.02 and 0.04, respectively, while keeping other conditions the same as the pure SCCO2. The equilibrium solubility of glycyrrhizin in SCCO2/ethanol (y′) and cosolvent effect factor ( f) are listed in Table 4. The cosolvent effect factor is defined as eq 1:

f=

y′ y

(1)

As shown in Table 4, ethanol, as a cosolvent, greatly increased the glycyrrhizin solubility. The value of y′ increases from 2.61 × 10−6 to 27.30 × 10−6, and from 4.97 × 10−6 to 1746

DOI: 10.1021/je5011328 J. Chem. Eng. Data 2015, 60, 1744−1749

Journal of Chemical & Engineering Data

Article

Figure 4. Experimental solubility of glycyrrhizin (y) in SCCO2 as a function of pressure: ●, 308 K; ⧫, 318 K; ▲, 328 K.

Table 4. Solubility (y′) of Glycyrrhizin in SCCO2 with Cosolvent Ethanol at Mole Fractions of 0.02 and 0.04 and Cosolvent Effect Factor ( f) at Temperatures of (308, 318, and 328) K and Pressures from (9 to 21) MPa Ta/K

P/MPa

y′0.02b·106

f 0.02

y′0.04·106

f 0.04

308

9 12 15 18 21 9 12 15 18 21 9 12 15 18 21

2.61 3.69 5.60 7.63 9.52 3.81 7.12 10.94 15.16 18.25 4.73 9.80 15.11 21.56 27.30

1.70 1.79 2.58 3.07 3.20 1.68 2.23 2.84 3.19 3.19 2.31 2.54 2.81 3.10 3.17

4.97 12.43 20.99 29.97 37.29 5.18 15.32 26.62 37.41 45.57 6.40 18.86 32.70 44.64 54.30

3.22 6.04 9.68 12.05 12.53 2.29 4.79 6.91 7.87 7.96 3.12 4.90 6.09 6.42 6.31

318

328

a

Standard uncertainties u are the following: u(T) = 0.1 K, u(P) = 0.2 MPa, u(y) = 1.30 %. bThe subscripts of 0.02 and 0.04 represent the cosolvent mole fractions used.

Figure 6. Test of consistencies for solubility data of glycyrrhizin in pure SCCO2 using the (a) Chrastil, (b) Bartle, and (c) MendezSantiago and Teja (MST) models.

54.30 × 10−6 at ethanol mole fraction of 0.02 and 0.04, separately. The maximum value of f reaches 12.53 when the pressure, temperature, and ethanol mole fraction are 21 MPa, 308 K, and 0.04, respectively. Figure 5 shows the variation trends of the solubility in SCCO2 with cosolvent at different pressures and temperatures. Similar to the situation in pure SCCO2, the value of y′ increases with increasing both pressure and temperature, but much more, especially at the more mole fraction of ethanol. On the one hand, the existence of cosolvent may increase the density of mixed fluid, improving the solubility of glycyrrhizin in SCCO2. On the other hand, the polarity of

Figure 5. Experimental solubility of glycyrrhizin (y) in SCCO2 as a function of pressure with cosolvent ethanol in mole fractions 0.02: ●, 308 K; ⧫, 318 K; ▲, 328 K; and 0.04: ○, 308 K; ◇, 318 K; △, 328 K. 1747

DOI: 10.1021/je5011328 J. Chem. Eng. Data 2015, 60, 1744−1749

Journal of Chemical & Engineering Data

Article

MST-S models get similar correlated results, and their AARDs are lower than those of models for solubility in pure SCCO2, which indicates that the solubility of glycyrrhizin is predicted more correctly when using cosolvent. Figures 6 and 7 show the graphic correlated results of the five semi-empirical models. In Figure 6, the plots transformed by the Chrastil, Bartle, and MST models against the density of SCCO2 or its logarithm value are nearly straight lines. Similar results are obtained for the Chrastil-G and MST-S models applied for data with cosolvent in Figure 7. These results guarantee that these density-based models can be used to accurately calculate the solubility of glycyrrhizin in pure SCCO2 and cosolvent-added SCCO2.



CONCLUSION Equilibrium solubility data for glycyrrhizin in pure SCCO2 and cosolvent-added SCCO2 over the pressure ranging from (9 to 21) MPa at the temperature of (308, 318, and 328) K are presented. The solubility of glycyrrhizin changed between 1.54 × 10−6 and 8.61 × 10−6 with the change of pressure and temperature in pure SCCO2, while higher values of 2.61 × 10−6 to 54.30 × 10−6 are obtained in cosolvent-added SCCO2 at ethanol mole fractions of 0.02 and 0.04. Three density based semi-empirical models (Chrastil, Bartle, and Mendez-Santiago and Teja (MST) models) give good correlation results in pure SCCO2 with average absolute relative deviation (AARD) of (4.23 to 6.82) %, while two different models (modified Chrastil and modified MST models) get more accuracy results in cosolvent-added SCCO2 with AARD of (3.38 and 3.85) %, suggesting ethanol can be an efficient cosolvent for increasing the solubility of glycyrrhizin in SCCO2.



Figure 7. Test of consistencies for solubility data of glycyrrhizin in SCCO2 with cosolvent ethanol using the (d) Chrastil modified by González (Chrastil-G) and (e) Mendez-Santiago and Teja-Sauseau (MST-S) models. ●, data at cosolvent mole fraction of 0.02; ▲, data at cosolvent mole fraction of 0.04.

Solubility of salicylic acid in pure SCCO2. The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/je5011328.



100 N

N

∑ 1

*E-mail: [email protected]. Tel: +86-021-54743274. Funding

We are thankful for the support by the Funding of National Natural Science Foundation of China (20976103). Notes

The authors declare no competing financial interest.



REFERENCES

(1) Girotra, P.; Singh, S. K.; Nagpal, K. Supercritical fluid technology: A promising approach in pharmaceutical research. Pharm. Dev. Technol. 2013, 18, 22−38. (2) Brunner, G. Supercritical fluids: Technology and application to food processing. J. Food Eng. 2005, 67, 21−33. (3) Reverchon, E.; Adami, R. Nanomaterials and supercritical fluids. J. Supercrit. Fluids 2006, 37, 1−22. (4) Sahena, F.; Zaidul, I. S. M.; Jinap, S.; Karim, A. A.; Abbas, K. A.; Norulaini, N. A. N.; Omar, A. K. M. Application of supercritical CO2 in lipid extraction - A review. J. Food Eng. 2009, 95, 240−253. (5) Savage, P. E.; Gopalan, S.; Mizan, T. I.; Martino, C. J.; Brock, E. E. Reactions at supercritical conditions: applications and fundamentals. AIChE J. 1995, 41, 1723−1778.

|ycal − yexp | yexp

AUTHOR INFORMATION

Corresponding Author

the modified solvent may be increased, and the molecular interaction between the cosolvent and the solute enhances the solubility, which is more important for the polar solute. Solubility Correlation. The equilibrium solubility data in pure SCCO2 and cosolvent-added SCCO2 have been correlated by several semi-empirical models. The detail description of equations and the correlation parameters are presented in Table 2. The agreement of these models in correlating experimental solubility data is assessed from the corresponding absolute average relative deviation (AARD), defined as eq 2 AARD(%) =

ASSOCIATED CONTENT

S Supporting Information *

(2)

where ycal is the calculated solubility, yexp is the experimental solubility, and N is the total number of data points. The AARDs of the calculated equilibrium solubility for all models are below 6.82 %, showing satisfactory accuracy of the experimental results. For the glycyrrhizin solubility in pure SCCO2, the result of the Chrastil model obtains the best agreement (AARD is 4.23 %) compared with others. However, for the solubility in cosolvent-added SCCO2, the Chrastil-G and 1748

DOI: 10.1021/je5011328 J. Chem. Eng. Data 2015, 60, 1744−1749

Journal of Chemical & Engineering Data

Article

(6) Cocero, M. J.; Martín, A.; Mattea, F.; Varona, S. Encapsulation and co-precipitation processes with supercritical fluids: Fundamentals and applications. J. Supercrit. Fluids 2009, 47, 546−555. (7) Garlapati, C.; Madras, G. Solubilities of hexadecanoic and octadecanoic acids in supercritical CO with and without cosolvents. J. Chem. Eng. Data 2008, 53, 2913−2917. (8) Coimbra, P.; Blanco, M. R.; Costa Silva, H. S. R.; Gil, M. H.; De Sousa, H. C. Experimental determination and correlation of artemisinin’s solubility in supercritical carbon dioxide. J. Chem. Eng. Data 2006, 51, 1097−1104. (9) Sparks, D. L.; Estévez, L. A.; Hernandez, R.; Barlow, K.; French, T. Solubility of nonanoic (pelargonic) acid in supercritical carbon dioxide. J. Chem. Eng. Data 2008, 53, 407−410. (10) Bai, Y.; Yang, H. J.; Quan, C.; Guo, C. Y. Solubilities of 2,2′bipyridine and 4,4′-dimethyl-2,2′- bipyridine in supercritical carbon dioxide. J. Chem. Eng. Data 2007, 52, 2074−2076. (11) Dilek, C.; Manke, C. W.; Gulari, E. Phase behavior of β-d galactose pentaacetate-carbon dioxide binary system. Fluid Phase Equilib. 2006, 239, 172−177. (12) Montañeś , F.; Fornari, T.; Stateva, R. P.; Olano, A.; Ibáñez, E. Solubility of carbohydrates in supercritical carbon dioxide with (ethanol + water) cosolvent. J. Supercrit. Fluids 2009, 49, 16−22. (13) Cinatl, J.; Morgenstern, B.; Bauer, G.; Chandra, P.; Rabenau, H.; Doerr, H. W. Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus. Lancet 2003, 361, 2045− 2046. (14) Genovese, T.; Menegazzi, M.; Mazzon, E.; Crisafulli, C.; Di Paola, R.; Dal Bosco, M.; Zou, Z.; Suzuki, H.; Cuzzocrea, S. Glycyrrhizin reduces secondary inflammatory process after spinal cord compression injury in mice. Shock 2009, 31, 367−375. (15) Crance, J. M.; Scaramozzino, N.; Jouan, A.; Garin, D. Interferon, ribavirin, 6-azauridine and glycyrrhizin: Antiviral compounds active against pathogenic flaviviruses. Antiviral Res. 2003, 58, 73−79. (16) Sasaki, H.; Takei, M.; Kobayashi, M.; Pollard, R. B.; Suzuki, F. Effect of glycyrrhizin, an active component of licorice roots, on HIV replication in cultures of peripheral blood mononuclear cells from HIV-seropositive patients. Pathobiology 2002, 70, 229−236. (17) Mousa, N. A.; Siaguru, P.; Wiryowidagdo, S.; Wagih, M. E. Establishment of regenerative callus and cell suspension system of licorice (Glycyrrhiza glabra) for the production of the sweetener glycyrrhizin in vitro. Sugar Tech 2007, 9, 72−82. (18) Kim, N. C.; Kinghorn, A. D. Highly sweet compounds of plant origin. Arch. Pharm. Res. 2002, 25, 725−746. (19) Kim, H. S.; Lee, S. Y.; Kim, B. Y.; Lee, E. K.; Ryu, J. H.; Lim, G. B. Effects of modifiers on the supercritical CO2 extraction of glycyrrhizin from licorice and the morphology of licorice tissue after extraction. Biotechnol. Bioprocess Eng. 2004, 9, 447−453. (20) Jin, S.; Fu, S.; Han, J.; Jin, S.; Lv, Q.; Lu, Y.; Qi, J.; Wu, W.; Yuan, H. Improvement of oral bioavailability of glycyrrhizin by sodium deoxycholate/phospholipid-mixed nanomicelles. J. Drug Targeting 2012, 20, 615−622. (21) Jung, J.; Perrut, M. Particle design using supercritical fluids: Literature and patent survey. J. Supercrit. Fluids 2001, 20, 179−219. (22) Fages, J.; Lochard, H.; Letourneau, J. J.; Sauceau, M.; Rodier, E. Particle generation for pharmaceutical applications using supercritical fluid technology. Powder Technol. 2004, 141, 219−226. (23) Škerget, M.; Knez, Z.; Knez-Hrnčič, M. Solubility of solids in sub- and supercritical fluids: A review. J. Chem. Eng. Data 2011, 56, 694−719. (24) Chrastil, J. Solubility of solids and liquids in supercritical gases. J. Phys. Chem. 1982, 86, 3016−3021. (25) Bartle, K. D.; Clifford, A. A.; Jafar, S. A.; Shilstone, G. F. Solubilities of solids and liquids of low volatility in supercritical carbon dioxide. J. Phys. Chem. 1991, 20, 713−756. (26) Méndez-Santiago, J.; Teja, A. S. The solubility of solids in supercritical fluids. Fluid Phase Equilib. 1999, 158−160, 501−510. (27) González, J. C.; Vieytes, M. R.; Botana, A. M.; Vieites, J. M.; Botana, L. M. Modified mass action law-based model to correlate the

solubility of solids and liquids in entrained supercritical carbon dioxide. J. Chromatogr., A 2001, 910, 119−125. (28) Sauceau, M.; Letourneau, J. J.; Richon, D.; Fages, J. Enhanced density-based models for solid compound solubilities in supercritical carbon dioxide with cosolvents. Fluid Phase Equilib. 2003, 208, 99− 113. (29) Gurdial, G. S.; Foster, N. R. Solubility of o-hydroxybenzoic acid in supercritical carbon dioxide. Ind. Eng. Chem. Res. 1991, 30, 575− 580. (30) Ke, J.; Mao, C.; Zhong, M.; Han, B.; Yan, H. Solubilities of salicylic acid in supercritical carbon dioxide with ethanol cosolvent. J. Supercrit. Fluids 1996, 9, 82−87. (31) Wang, T. C.; Lee, P. Y. Measurement and correlation for the solid solubility of antioxidants d -isoascorbic acid and calcium l -ascorbate dihydrate in supercritical carbon dioxide. J. Chem. Eng. Data 2014, 59, 613−617. (32) Jin, J. S.; Ning, Y. Y.; Hu, K.; Wu, H.; Zhang, Z. T. Solubility of p-nitroaniline in supercritical carbon dioxide with and without mixed cosolvents. J. Chem. Eng. Data 2013, 58 (6), 1464−1469.

1749

DOI: 10.1021/je5011328 J. Chem. Eng. Data 2015, 60, 1744−1749