Differential Scanning Calorimetry Data and Solubility of Rosmarinic

Article pubs.acs.org/jced

Differential Scanning Calorimetry Data and Solubility of Rosmarinic Acid in Different Pure Solvents and in Binary Mixtures (Methyl Acetate + Water) and (Ethyl Acetate + Water) from 293.2 to 313.2 K Abdelkarim Aydi,† Carlos Alberto Claumann,‡ André Wüst Zibetti,*,§ and Manef Abderrabba∥ †

Department of Chemical and Materials Engineering, College of Engineering, Northern Border University, P.O. Box 1321, Arar, Kingdom of Saudi Arabia ‡ Laboratorio de Controle de Processos, Departments of Chemical Engineering and Food Engineering, Universidade Federal de Santa Catarina (UFSC), P.O. Box 476, Florianópolis, 88010-970, SC, Brazil § Department of Informatics and Statistics (INE), Universidade Federal de Santa Catarina (UFSC), P.O. Box 476, 88040-900, Florianópolis, SC, Brazil ∥ Laboratoire Matériaux Molécules et Applications-IPEST, La Marsa 2070, Tunisie ABSTRACT: The thermodynamic melting properties (temperature, enthalpy, and entropy) of rosmarinic acid were experimentally determined via differential scanning calorimetry. The solubility of rosmarinic acid in three solvents (water, methyl acetate, and ethyl acetate), and in their binary mixtures, were determined. The data obtained experimentally were correlated by way of a modified Apelblat model. Through solubility measurements, the activity coefficient was calculated for the process of dissolving the rosmarinic acid in pure solvents and in their mixtures.

1. INTRODUCTION Rosmarinic acid (RA), a phenolic compound mainly extracted from plants of the Lamiaceae family, is an ester of caffeic acid and 3-(3,4-dihydroxyphenyl) lactic acid. An increasing number of studies report interest in scaling up rosmarinic acid production, due to its beneficial biological activity. The studied compound induces anti-inflammatory, anticancer, antioxidant, antiviral (anti-HIV), and several other effects.1−6 Studies reported that the extraction of RA from rosemary leaves could be carried out via different processes, mainly the extraction with solvent such as extraction and purification with a supercritical solvent. This technique is highly expensive and difficult to implement. Extraction with organic solvents is considered to be a good alternative for this process. Nevertheless, the choice of the suitable solvent is a crucial step, and it should satisfy several criteria such as price and environment.6−14 Although the selection of technology for obtaining the RA influences the amounts obtained, the solvent used and lab conditions are key to maximizing results. The proper choice of solvents for obtaining high value compounds, such as RA, depends on experimental data on its solubility in different solvents. Thus, ethyl and methyl acetate and their mixtures with water are selected for rosmarinic acid extraction. Thus, mapping the solubility of pure compounds in solvents and mixtures is critical for understanding the behavior of a given solute in different solvents. This study aims to provide © XXXX American Chemical Society

data on the solubility of a compound with high added value (RA) as well as data on its thermodynamic characteristics.

2. MATERIAL AND METHODS Rosmarinic acid C18H16O8 (MW = 360.31), ethyl acetate, and methyl acetate were supplied by Sigma-Aldrich (USA). Detailed information on the materials is shown in Table 1. The chemical structure of the rosmarinic acid is shown in Figure 1. Ultrapure water (conductivity around 1.5 μS cm−1) was used for all experiments. Table 1. Sources and Purity of Chemicals chemical name methyl acetate ethyl acetate rosmarinic acid water gallic acid a

source

purity (mass fraction)

Sigma-Aldrich ≥0.980 Sigma-Aldrich ≥0.998 Sigma-Aldrich ≥0.955 made from ultrapure water equipment Sigma-Aldrich ≥0.970

analysis method GCa GCa HPLCb HPLCb

b

Gas chromatography. High performance liquid chromatography.

Received: January 5, 2016 Accepted: October 20, 2016

A

DOI: 10.1021/acs.jced.6b00008 J. Chem. Eng. Data XXXX, XXX, XXX−XXX

Journal of Chemical & Engineering Data

Article

be determined directly from the α data as a function of temperature. Figure 2 shows variable α due to temperature for sample 3, beyond the baseline adopted. The curves for other samples displayed similar behavior. Figure 1. Molecular structure of rosmarinic acid.

2.1. Determination of Solubility of Rosmarinic Acid. Binary solvents were prepared by mass using a Sartorius CP225D analytical balance (±0.0001 g). An amount of 30 g (±0.0003 g) of binary solvents was introduced into a double jacketed reactor with the thermostat at (T ± 0.1) K (Polystat Huber CC2). Solid rosmarinic acid was added to the liquid phase until excess; the solution was continuously stirred with a magnetic stirrer; a sample of the liquid phase was taken through a 0.2-μm pore syringe filter were the equilibrium was checked (∼5 h); and the concentration was measured by UV/visible spectrophotometry (Beckman Coulter DU-520) at 328 nm. The calibration curve was prepared in methyl acetate. The rosmarinic acid solubility was determined through three (3) independent experiments and the reproducibility of data was within 3.0%. The solubility (expressed by molar fraction) for a pure solvent is given by eq 1: x RA =

mRA /MRA m mRA + Ms M RA

Figure 2. Fusion peak of rosmarinic acid obtained via DSC (10 K/min and gas purge N2 at 50 mL/min).

Using the data obtained from the DSC curves, the parameters for RA fusion were determined as follows: ΔHm, the fusion enthalpy, corresponds to the integral (area) between the α curve and its respective baseline. This estimate was performed numerically. Tm, the value of the fusion temperature, was taken to be the temperature to which the α curve shows the highest value. ΔSm, the fusion entropy, can be calculated from the estimated values ΔHm and Tm according to eq 4.

(1)

s

where mRA and ms are the masses of RA and its solvent, respectively. The MRA and Ms represent the molecular mass of the solute and solvent, respectively. Equation 1 can be used for a binary solvent mixture (water + ethyl acetate) and (water + methyl acetate) as given by eq 2: x RA =

mRA /MRA m + Mw +

mRA MRA

w

ms Ms

(2)

ΔSm =

where mRA, mw, ms represent the mass of RA, water, and organic solvent (ethyl acetate or methyl acetate), respectively. MRA, MW, Ms are the molecular masses of RA, water, and organic solvent (methyl acetate ethyl acetate), respectively. 2.2. Rosmarinic Acid Differential Scanning Calorimetry (DSC). RA DSC analysis was carried out in independent triplicate experiments, considering a heating rate of 10 K/min, using a nitrogen gas purge at 50 mL/min. The differential scanning calorimetry analyses (DSC) were conducted using the PerkinElmer equipment/Jade DSC (Intracooler SP). The masses of the samples (denominated 1, 2, and 3) were 3.6, 2.6, and 3.5 mg, respectively. To each sample a temperature scanning between 373.15 and 573.15 K was carried out, and for determining the parameters of RA fusion solely the range between 388.15 and 468.15 K was considered. The output provided by the DSC equipment is the heat flow (Q·) applied to the sample due to temperature; however, in order to obtain the parameters of fusion, it is more convenient to work with the ratio between Q· and the sample mass product by temperature gradients used, as shown in eq (3).

Q̇ α= mΔṪ

ΔHm Tm

(4)

3. ANALYSIS OF SOLUBILITY IN A SOLVENTS SYSTEM According to Sandler,15 the solubility of an arbitrary solid in a solvent (or a combination of solvents) may be obtained by equating the fugacities of the first during the solid and liquid phases, in accordance with eq 5. L

f iS (T , P) = f i̅ (T , P , Xi)

(5)

f Si (T,

where P) is the fugacity of the compound of interest during the solid phase and fLi̅ (T, P, Xi) is the fugacity of the compound of interest during the liquid phase. The fugacity of a component present in the liquid phase can be evaluated in accordance with eq 6. L

f i̅ (T , P , Xi) = Xiγi(T , P , X i)fiL (T , P)

(6)

Replacing eq 6 in eq 5 results in eq 7 for calculating the equilibrium of the phases: f iS (T , P) = Xiγi(T , P , Xi)fiL (T , P)

(7)

where γi denotes the coefficient of activity. In eq 7 the relationship between fugacities in pure states is directly related to the Gibbs free energy of solid fusion, as shown in eq 8.

(3)

Variable α displays the same specific heat units, wherein enthalpy of fusion (ΔHm) and temperature of fusion (Tm) can B


Journal of Chemical & Engineering Data fiL (T , P) ΔGfus = ln S RT f i (T , P )

Article

(8)

In eq 8 the term associated with ΔGfus depends only on the physical properties of the solute and the temperature used, being positive for temperatures below the melting solid. Seeing as such a condition is generally met, the influence of ΔGfus is to decrease the solubility of the solid. In the case of the activity coefficient of solute (γi), the smaller its value is, the greater is the solubility in the solvent. Applying eq 8 to eq 7 results in eq 9, the solid solubility (exemplifying for RA) due to the activity coefficient and the Gibbs free energy of fusion ln(Xi) = −ln(γi) −

ΔGfus RT

(9)

The Gibbs free energy of fusion can be calculated considering different stages:

Figure 3. Mass fraction solubility of gallic acid in water at different temperatures: (∗) this work−validation method; (+) literature values;16 (○) literature values.17

I. heating of the operating temperature T solid until the fusion temperature of Tm II. solid fusion at temperature Tm III. cooling of the fusion temperature Tm liquid (no freezing) until operating temperature T According to Sandler,15 ΔGfus can be calculated approximately as ΔGfus =

⎞ ΔHm ⎛ Tm ⎜ − 1⎟ ⎠ RTm ⎝ T

Table 2. Data Reported in Figure 3 at Temperature T and Pressure P = 0.1 MPad 100WGA T/K 293.15 298.15 303.15 308.15 313.15 318.15

(10)

In this study, the solubility of RA in different operating conditions was measured experimentally, as were the fusion parameters determined from DSC curves. Thus, it was possible to obtain an estimate of RA activity coefficients γRA in a solute concentration equal to the solubility, considering the different temperatures and solvent mixtures, isolating γRA in eq 9.

this work

Daneshfar et al. 2008

1.274 1.452 1.456 2.211 2.721

Lu and Lu 2007

1.516 1.615 2.367 2.54 3.429

0.96 1 1.38 1.79 2.36

100RD1

100RD2

−0.04408 −0.1092 −0.07056 0.06652

0.246468 0.311295 0.052198 0.190412 0.132672

a

WGA is the mass fraction of gallic acid in pure water. bRD1 is the relative error from Daneshfar et al. 2008. cRD2 is the relative error from Lu and Lu 2007. dStandard uncertainties u are u(T) = 0.05 K, ur(p) = 0.05, ur(w) = 0.03.

RD =

4. RESULTS AND DISCUSSION 4.1. Validation Method (Mass Fraction). To validate the method of the solubility measurement, the solubility of gallic acid in pure water was determined at the temperature range of (293.15 to 313.15) K. The experimental values shown in Figure 3 and Table 2 are compared with data reported in the literature16,17 (mass fraction). Despite the difference observed between our results and the results from literature (due to experimental error or/and analysis method), the reliability of the method of solubility measurement used in this work was proven. 4.2. Solubility (Mole Fraction). The solubility of rosmarinic acid xRA was determined for pure solvents (water, methyl acetate, and ethyl acetate) as well as in the binary solvent mixtures (water + methyl acetate (MA) and water + ethyl acetate (EA)), at different temperatures. For the binary mixtures, MA and ME molar fractions of (0.10, 0.30, 0.50, 0.70, and 0.90) were tested. The solubility data for water, methyl acetate, ethyl acetate, and binary mixtures are shown in Table 3. In addition, the prediction of the Apelblat xmod for xRA is shown, as will be described in section 4.3. In Table 3 the RD column means the {relative error} between the experimental data and the respective value predicted by the model, as per eq 11.

x RAi − xmodi x RAi

(11)

The relative average deviations (RAD) are calculated as follow, RAD =

1 n

n

∑ i=1

x RAi − xmodi x RAi

(12)

where n is the number of the experimental points, xmodi is the solubility calculated from the Apelblat equation, and xRAi represents the experimental solubility. On the basis of analysis of the data shown in Table 3 it can be concluded that the solubility of RA increases with the temperature and the molar fraction of methyl and ethyl acetates. 4.3. Apelblat Model Equation. The dependence of the solubility of RA with temperature in binary systems water + MA and water + EA can be described by the modified Apelblat eq eq 13, * ) = A + B + C ln(T ) ln(XRA T

(13)

where T is the absolute temperature (K), A, B(K), and C are empirical parameters determined through adjustments made to experimental data. C



Article

Table 3. Experimental Mole Fraction Solubilities (xRA) of Rosmarinic Acid (RA) in Liquid Solvents and Binary Solvent Mixtures at Temperature T and Pressure P = 0.1 MPae T/K 293.15 298.15 303.15 308.15 313.15 293.15 298.15 303.15 308.15 313.15 293.15 298.15 303.15 308.15 313.15 293.15 298.15 303.15 308.15 313.15 293.15 298.15 303.15 308.15 313.15 293.15 298.15 303.15 308.15 313.15 293.15 298.15 303.15 308.15 313.15

100xRA

100xmod

Water (ref 18) 1.3508 1.3095 1.5123 1.4860 1.6520 1.6827 1.8480 1.9017 2.0906 2.1450 Methyl Acetate 3.6308 3.8381 4.8990 4.5637 5.3257 5.4111 6.1886 6.3983 7.6442 7.5456 Ethyl Acetate 3.4496 3.6574 4.6575 4.3406 5.0632 5.1369 5.8798 6.0629 7.2195 7.1371 Water + Methyl Acetate, XMA = 1.4053 1.3899 1.7552 1.6442 1.8719 1.9396 2.0492 2.2821 2.8014 2.6781 Water + Methyl Acetate, XMA = 1.7595 1.7299 2.1234 2.0592 2.3622 2.4441 2.8005 2.8930 3.4871 3.4152 Water + Methyl Acetate, XMA = 2.1855 2.1752 2.6665 2.5840 2.9874 3.0609 3.5191 3.6160 4.3310 4.2606 Water + Methyl Acetate, XMA = 2.7792 2.7654 3.4076 3.2880 3.7827 3.8983 4.4841 4.6093 5.5308 5.4356

T/K

100RD 3.0540 1.7441 −1.8597 −2.9055 −2.6017

293.15 298.15 303.15 308.15 313.15

−5.7111 6.8434 −1.6034 −3.3891 1.2897

293.15 298.15 303.15 308.15 313.15

−6.0244 6.8044 −1.4558 −3.1146 1.1414

293.15 298.15 303.15 308.15 313.15

1.0951 6.3268 −3.6184 −11.3624 4.4029

293.15 298.15 303.15 308.15 313.15

1.6825 3.0274 −3.4656 −3.3002 2.0640

293.15 298.15 303.15 308.15 313.15

0.4714 3.0944 −2.4608 −2.7543 1.6254

293.15 298.15 303.15 308.15 313.15

0.10

0.30

0.50

100xRA

100xmod

Water + Methyl Acetate, XMA = 0.90 3.2293 3.2636 4.0464 3.8844 4.5204 4.6102 5.3078 5.4564 6.5351 6.4408 Water + Ethyl Acetate, XEA = 0.10 1.3292 1.3285 1.7048 1.5709 1.7615 1.8525 1.9553 2.1787 2.6768 2.5558 Water + Ethyl Acetate, XEA = 0.30 1.6918 1.6568 2.0269 1.9646 2.2333 2.3231 2.6477 2.7397 3.2969 3.2225 Water + Ethyl Acetate, XEA = 0.50 2.0855 2.0511 2.4831 2.4364 2.8082 2.8861 3.3435 3.4094 4.0765 4.0170 Water + Ethyl Acetate, XEA = 0.70 2.6406 2.6362 3.2558 3.1220 3.5596 3.6870 4.2214 4.3427 5.1960 5.1017 Water + Ethyl Acetate, XEA = 0.90 3.0396 3.0816 3.8470 3.6712 4.2758 4.3611 4.9904 5.1663 6.2091 6.1039

100RD −1.0620 4.0031 −1.9849 −2.8007 1.4436 0.0568 7.8526 −5.1653 −11.4277 4.5181 2.0702 3.0713 −4.0234 −3.4754 2.2575 1.6498 1.8790 −2.7740 −1.9701 1.4609 0.1640 4.1102 −3.5803 −2.8726 1.8134 −1.3796 4.5693 −1.9959 −3.5259 1.6941

a

0.70

XMA is the molar fraction of methyl acetate in the (water + methyl acetate) binary mixture solvent. bXEA is the molar fraction of ethyl acetate in the (water + ethyl acetate) binary mixture solvent. cRD is the relative error. dxmod is the solubility calculated from the Apelblat equation. eStandard uncertainties u are u(T) = 0.05 K, ur(p) = 0.05, ur(x) = 0.03.

0.4973 3.5096 −3.0580 −2.7921 1.7221

The parameters of the Apelblat model adjusted for water, MA, EA, and the binary solvent systems (water + MA and water + EA) are shown in Table 4. The parameters were obtained by minimizing the square error of approximation of the experimental values between the data and the model. As can be seen in Table 4, except in the case of pure water there is no abrupt variation in the parameters of the Apelblat model in the water + MA and water + EA systems, considering the different solvent ratios. This is a desirable characteristic, as it will imply in a reliable estimate of the solubility of RA in solvent proportions different from those considered in this work, by interpolation of different models obtained. A comparison between the performances of the model and those of the experimental solubility data is shown in Figures 4 and 5 for pure solvents (water, methyl acetate, and ethyl acetate) and systems water + MA and water + EA, respectively.

The experimental data are given in Table 2 and the parameters used in the Apelblat model are shown in Table 4. The satisfactory adjustment of the model to the experimental data can be observed in Figures 4 and 5. In addition, the highest value of 100RAD (numerically equal to the relative error percentage) observed was less than 5.8, which qualifies the measured data, the Apelblat correlation, and its respective parameters, to serve as the basis of studies that aim at stimulating extraction, concentration, and purification of rosmarinic acid. 4.4. Parameters of Fusion and Activity Coefficients. The parameters of fusion were determined from the experimental DSC data. Following the procedure described in said section, and converting parameters of fusion to molar units, the parameters shown in Table 5 were obtained. The temperature of RA fusion obtained experimentally in this study D



Article

Table 4. Parameters of the Apelblat Equation for Rosmarinic Acid in Different Pure Solvents and in Binary Solvent Mixtures (Water + Methyl Acetate and Water + Ethyl Acetate) solvent

A

B (K)

C

R2

100RAD

water methyl acetate ethyl acetate water + MA XMA = 0.10 XMA = 0.30 XMA = 0.50 XMA = 0.70 XMA = 0.90 water + EA XEA = 0.10 XEA = 0.30 XEA = 0.50 XEA = 0.70 XEA = 0.90

−47.7000 −62.6003 −61.9980

40.0905 52.1860 51.6976

7.6096 10.4146 10.3004

97.2469 97.5822 97.6035

2.4330 3.7674 3.7081

−61.8764 −63.7812 −62.8564 −62.9184 −63.1026

51.7758 53.3041 52.4999 52.5090 52.6305

10.1086 10.4815 10.3595 10.4127 10.4742

91.9230 98.5660 99.0197 98.8218 98.9542

5.3611 2.7079 2.0813 2.3158 2.2589

−61.7900 −62.5203 −62.9082 −61.6044 −63.4834

51.7125 52.2727 52.5533 51.4342 52.9548

10.0855 10.2526 10.3583 10.1736 10.5309

90.8192 98.2259 99.2813 98.4887 98.5787

5.8041 2.9795 1.9468 2.5081 2.6330

Figure 5. Plot of 100xRA solubility of rosmarinic acid against temperature T/K, and fitting curves from the Apelblat equation applied to different pure solvents and for binary solvent mixture (water + ethyl acetate).

a

XMA is the molar fraction of methyl acetate in the (water + methyl acetate) binary mixture solvent. bXEA is the molar fraction of ethyl acetate in the (water + ethyl-acetate) binary mixture solvent. cRAD is the relative average deviation and R 2 is the coefficient of determination.

Table 5. Parameters of Fusion of Rosmarinic Acid Obtained Experimentally (p = 0.1 MPa) parameters

sample 1

sample 2

sample 3

averagea

ΔfusHm [kJ/mol] Tm [K] Sm [J/(mol·K)]

16.58 432.46 38.34

15.66 433.98 36.08

16.93 435.88 38.85

16.39 ± 0.66 434.11 ± 1.71 37.75 ± 1.47

Arithmetic mean ± standard deviation. Standard uncertainties u is u(p) = 0.02 MPa.

a

Table 6. Estimated Activity Coefficient of Rosmarinic Acid (γRA) in Different Pure Solvents at Different Temperatures T [K]

water

methyl acetate

ethyl acetate

293.15 298.15 303.15 308.15 313.15

8.9237 8.9051 9.0752 8.9995 8.7956

3.3199 2.7491 2.8150 2.6874 2.4055

3.4943 2.8916 2.9610 2.8285 2.5470

Table 7. Estimated Activity Coefficient of Rosmarinic Acid (γRA) in Water + Methyl Acetate at Different Temperatures Figure 4. Plot of 100 xRA solubility of rosmarinic acid against temperature T/K, and fitting curves from the Apelblat equation applied for different pure solvents and for the binary solvent mixture (water + methyl acetate).

T [K] 293.15 298.15 303.15 308.15 313.15

(434.11 ± 1.71 K) was lower than that reported by Ellis and Towers (445.12 to 448.15 K);19 this may be associated with differences in the degree of purity of the RA used. By using the parameters of fusion and the solubility data, and by isolating γRA from eq 9, an estimate of RA activity coefficients in different temperature and systems conditions is obtained; this is shown in Tables 6 to 8. Molar fractions determined experimentally were used in calculating the values shown in these tables. According to Tables 6 to 8, the RA activity coefficient displays a tendency to decrease with increasing temperature and with fractions of methyl and ethyl acetate. This agrees with the behavior observed in Table 3 because the smaller is the γi of

XMA = 0.10 XMA = 0.30 XMA = 0.50 XMA = 0.70 8.5776 7.6729 8.0091 8.1158 6.5639

6.8507 6.3423 6.3466 5.9385 5.2732

5.5153 5.0507 5.0184 4.7259 4.2458

4.3372 3.9522 3.9633 3.7089 3.3247

XMA = 0.90 3.7326 3.3283 3.3165 3.1333 2.8137

Table 8. Estimated Activity Coefficient of Rosmarinic Acid (γRA) in Water + Ethyl Acetate at Different Temperatures

E

T [K]

XEA = 0.10

XEA = 0.30

XEA = 0.50

XEA = 0.70

XEA = 0.90

293.15 298.15 303.15 308.15 313.15

9.0684 7.9000 8.5111 8.5058 6.8695

7.1248 6.6445 6.7130 6.2814 5.5774

5.7800 5.4237 5.3387 4.9741 4.5107

4.5649 4.1365 4.2118 3.9397 3.5390

3.9656 3.5008 3.5063 3.3326 2.9615



Article

oil from Rosmarinus officinalis. J. Chromatogr. A 2011, 1218, 8480− 8489. (12) Peng, C.-H.; Su, J.-D.; Chyau, C.-C.; Sung, T.-Y.; Ho, S.-S.; Peng, C.-C.; Peng, R. Y. Supercritical Fluid Extracts of Rosemary Leaves Exhibit Potent Anti-Inflammation and Anti-Tumor Effects. Biosci., Biotechnol., Biochem. 2007, 71, 2223−2232. (13) Durling, N.; Catchpole, O.; Grey, J.; Webby, R.; Mitchell, K.; Foo, L.; Perry, N. Extraction of phenolics and essential oil from dried sage (Salvia officinalis) using ethanol−water mixtures. Food Chem. 2007, 101, 1417−1424. (14) Navarrete, A.; Herrero, M.; Martín, A.; Cocero, M. J.; Ibáñez, E. Valorization of solid wastes from essential oil industry. J. Food Eng. 2011, 104, 196−201. (15) Sandler, S. I. Chemical and Engineering Thermodynamics; Wiley: New York, NY, 1989; Vol. 1. (16) Daneshfar, A.; Ghaziaskar, H. S.; Homayoun, N. Solubility of Gallic Acid in Methanol, Ethanol, Water, and Ethyl Acetate. J. Chem. Eng. Data 2008, 53, 776−778. (17) Lu, L.-L.; Lu, X.-Y. Solubilities of Gallic Acid and Its Esters in Water. J. Chem. Eng. Data 2007, 52, 37−39. (18) Wüst Zibetti, A.; Aydi, A.; Claumann, C. A.; Eladeb, A.; Adberraba, M. Correlation of solubility and prediction of the mixing properties of rosmarinic acid in different pure solvents and in binary solvent mixtures of ethanol+water and methanol+water from (293.2 to 318.2) K. J. Mol. Liq. 2016, 216, 370−376. (19) Ellis, B. E.; Towers, G. H. Biogenesis of rosmarinic acid in Mentha. Biochem. J. 1970, 118, 291−297.

a solute in a solvent system, the greater is the affinity the solution will have with it.

5. CONCLUSIONS In this work, new data were provided for the solubility of rosmarinic acid in binary solvent mixtures (methyl acetate + water) and (ethyl acetate + water) at temperatures ranging from (293.2 to 313.2 K). Additionally, experimental enthalpy, entropy, and fusion temperature data were obtained for RA from DSC tests, as were estimates of activity coefficient of RA in pure solvents. The solubility of rosmarinic acid in solvent mixtures increases with increasing temperatures, while it decreases with the increase of water content in the mixture. The solubilities calculated by the modified Apelblat equation show good agreement with the experimental data.

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AUTHOR INFORMATION

Corresponding Author

*Tel: +55 48 3721 4705. E-mail: [email protected]; [email protected]. Notes

The authors declare no competing financial interest.

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REFERENCES

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Differential Scanning Calorimetry Data and Solubility of Rosmarinic

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