Food Chemistry 188 (2015) 57–61
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Food Chemistry journal homepage: www.elsevier.com/locate/foodchem
Solubility and thermodynamic behavior of vanillin in propane-1, 2-diol + water cosolvent mixtures at different temperatures Faiyaz Shakeel a,b,⇑, Nazrul Haq a,b, Nasir A. Siddiqui c, Fars K. Alanazi b, Ibrahim A. Alsarra a,b a
Center of Excellence in Biotechnology Research, College of Science, King Saud University, P.O. Box 2460, Riyadh 11451, Saudi Arabia Kayyali Chair for Pharmaceutical Industry, Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia c Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia b
a r t i c l e
i n f o
Article history: Received 2 March 2015 Received in revised form 24 April 2015 Accepted 27 April 2015 Available online 27 April 2015 Keywords: Cosolvent mixture Mathematical models Propane-1,2-diol Solubility Thermodynamics Vanillin
a b s t r a c t The solubilities of bioactive compound vanillin were measured in various propane-1,2-diol + water cosolvent mixtures at T = (298–318) K and p = 0.1 MPa. The experimental solubility of crystalline vanillin was determined and correlated with calculated solubility. The results showed good correlation of experimental solubilities of crystalline vanillin with calculated ones. The mole fraction solubility of crystalline vanillin was recorded highest in pure propane-1,2-diol (7.06 102 at 298 K) and lowest in pure water (1.25 103 at 298 K) over the entire temperature range investigated. Thermodynamic behavior of vanillin in various propane-1,2-diol + water cosolvent mixtures was evaluated by Van’t Hoff and Krug analysis. The results showed an endothermic, spontaneous and an entropy-driven dissolution of crystalline vanillin in all propane-1,2-diol + water cosolvent mixtures. Based on solubility data of this work, vanillin has been considered as soluble in water and freely soluble in propane-1,2-diol. Ó 2015 Elsevier Ltd. All rights reserved.
1. Introduction Vanillin is a phenolic aldehyde (Fig. 1) which is available commercially as a white to slightly yellow crystalline powder (Noubigh, Cherif, Provost, & Abderrabba, 2008). It is commonly used flavoring agent which is obtained from the bean or pod of Vanilla orchid (Kumar, Sharma, & Mishra, 2012). Therapeutically, it has been investigated as antioxidant, antimicrobial and antimutagenic although clinical trials are lacking (Kayaci & Uyar, 2012; Kumar et al., 2012; Peng et al., 2010). The strong antioxidant activity of vanillin is mainly due to the presence of phenolic compounds (Shakeel, Haq, & Siddiqui, 2015). It has been reported as soluble in water and freely soluble in propane-1,2-diol at 298 K (Noubigh et al., 2008; Shakeel, Haq, & Siddiqui, 2015). The solubility of bioactive compounds in cosolvent mixtures is one of the most important physicochemical parameter which is useful in purification, crystallization, preformulation studies and formulation development of these bioactive compounds (Shakeel & Anwer, 2015; Shakeel, Haq, Alanazi, & Alsarra, 2015; Shakeel, Haq, Siddiqui, Alanazi, & Alsarra, 2015). Propane-1,2-diol [also known as propylene glycol (PG)] is one of the commonly used cosolvent for solubilization ⇑ Corresponding author at: Center of Excellence in Biotechnology Research, College of Science, King Saud University, P.O. Box 2460, Riyadh 11451, Saudi Arabia. E-mail address: [email protected] (F. Shakeel). http://dx.doi.org/10.1016/j.foodchem.2015.04.113 0308-8146/Ó 2015 Elsevier Ltd. All rights reserved.
and stabilization of drugs in an aqueous media (Bhat, Haq, & Shakeel, 2014; Delgado, Pena, & Martinez, 2014; Munoz, Delgado, Pena, Jouyban, & Martinez, 2015; Zeng et al., 2014). Various mathematical models have been developed to evaluate the influence of temperature on solubility of solute but the modified Apelblat and Van’t Hoff models are the commonly used models for this purpose (Apelblat & Manzurola, 1999; Manzurola & Apelblat, 2002; Shakeel, Haq, & Siddiqui, 2015). However, the log-linear model of Yalkowsky is commonly used model to evaluate the influence of cosolvent mixture on solubility of solute (Yalkowsky & Roseman, 1981). The temperature dependent solubilities of crystalline vanillin in various propane-1,2-diol + water cosolvent mixtures are not available in literature. Therefore, in this work, the solubilities of bioactive compound vanillin in various propane-1,2-diol + water cosolvent mixtures were measured and correlated at T = (298–318) K and p = 0.1 MPa using an isothermal method reported by Higuchi & Connors (1965). From the solubility data of vanillin, various thermodynamic parameters such as standard dissolution enthalpy (DsolH0), standard dissolution entropy (DsolS0) and standard Gibbs free energy (DsolG0) for vanillin dissolution were also determined. The solubility data of this work could be useful in preformulation studies and formulation development of vanillin due to freely soluble nature of vanillin in propane-1,2-diol.
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F. Shakeel et al. / Food Chemistry 188 (2015) 57–61 Table 2 Experimental mole fraction solubilities (xe) of crystalline vanillin against mass fraction of propane-1,2-diol (m) in various propane-1,2-diol + water cosolvent mixtures at temperatures T = (298–318) K and pressure p = 0.1 MPa.a m
xe
0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
Fig. 1. Chemical structure of crystalline vanillin.
2. Experimental
T = 298 K
T = 303 K
T = 308 K
T = 313 K
T = 318 K
1.25 103 1.91 103 2.88 103 4.22 103 6.32 103 9.45 103 1.42 102 2.13 102 3.12 102 4.75 102 7.06 102
1.55 103 2.31 103 3.40 103 4.89 103 7.39 103 1.11 102 1.61 102 2.36 102 3.46 102 5.13 102 7.49 102
1.89 103 2.76 103 3.94 103 5.80 103 8.62 103 1.27 102 1.82 102 2.59 102 3.80 102 5.44 102 7.79 102
2.22 103 3.19 103 4.52 103 6.50 103 9.84 103 1.44 102 2.03 102 2.82 102 4.11 102 5.74 102 8.17 102
2.60 103 3.72 103 5.20 103 7.53 103 1.09 102 1.60 102 2.22 102 3.06 102 4.41 102 6.11 102 8.63 102
a The standard uncertainties u are u(T) = 0.16 K, ur(m) = 0.1%, u(p) = 0.003 MPa and ur(xe) = 1.35%.
2.1. Materials Vanillin was obtained from Sigma Aldrich (St. Louis, MO). Propane-1,2-diol was obtained from Fluka Chemicals (Busch, Switzerland). High performance liquid chromatographic (HPLC) grade acetonitrile and acetone were obtained from Acros Organics (Hamilton, NJ). HPLC grade water was obtained from Milli-Q water purification unit (Berlin, Germany). All the materials used in this work were of high purity (Table 1). 2.2. Measurement of vanillin solubility The mole fraction solubility of crystalline vanillin against mass fraction of propane-1,2-diol (m) in various propane-1,2-diol + water cosolvent mixtures at T = (298–318) K at p = 0.1 MPa was determined using an isothermal method (Higuchi & Connors, 1965). The excess amount of solute was added in known amounts of propane-1,2-diol + water cosolvent mixtures in triplicates. All the samples were vortex mixed for 5 min and transferred to biological shaker (Julabo, PA) for continuous shaking at 100 rpm for 72 h to reach equilibrium. The time period of 72 h was enough to reach equilibrium as reported previously (Shakeel, Haq, & Siddiqui, 2015). The remaining procedure was adopted from previous article (Shakeel, Haq, & Siddiqui, 2015). The quantification of vanillin in solubility samples was carried out by reversed phase HPLC method at the wavelength of 220 nm using ternary mixture of acetonitrile:water:acetone (7:2:1% v/v) as a mobile phase at flow rate of 1.0 mL min1 (Shakeel, Haq, & Siddiqui, 2015). The experimental solubilities (xe) of vanillin in various propane-1, 2-diol + water cosolvent mixtures were calculated as reported in literature (Shakeel, Haq, & Siddiqui, 2015). 3. Results and discussion 3.1. Measured solubility data of vanillin The measured solubility data of crystalline vanillin in various propane-1,2-diol + water cosolvent mixtures at T = (298–318) K and p = 0.1 MPa are presented in Table 2. The solubility data and
thermodynamic behavior of vanillin in propane-1,2-diol + water cosolvent mixtures have not been reported in literature. However, it has been reported as soluble in pure water and freely soluble in pure propane-1,2-diol (Shakeel, Haq, & Siddiqui, 2015). The mole fraction solubility of crystalline vanillin in pure water at T = 298 K has been reported as 1.17 103 and 1.22 103 by Noubigh et al. (2008) and Shakeel, Haq, and Siddiqui (2015), respectively (Noubigh et al., 2008; Shakeel, Haq, & Siddiqui, 2015). However, the mole fraction solubility of crystalline vanillin in pure propane-1,2-diol at T = 298 K has been reported as 7.15 102 (Shakeel, Haq, & Siddiqui, 2015). In this work, the mole fraction solubility of crystalline vanillin in pure water and pure propane-1,2-diol at T = 298 K was recorded as 1.25 103 and 7.06 102, respectively. The experimental solubilities of vanillin were in good agreement with literature solubilities of vanillin in water and propane-1,2-diol at T = 298 K. The graphical correlation between experimental and literature solubilities of vanillin in water and propane-1,2-diol at T = (298–318) K and p = 0.1 MPa are also presented in Figs. S1 and S2, respectively. The results showed good correlation of experimental solubilities of vanillin in water and propane-1,2-diol over the entire temperature range investigated. In general, the xe values of crystalline vanillin were found to be increasing with increase in temperature and mass fraction of propane-1,2-diol in propane-1,2-diol + water cosolvent mixtures over the entire temperature range investigated. The xe values of crystalline vanillin were observed highest in pure propane-1,2-diol (7.06 102 at T = 298 K) over the entire temperature range investigated. However, the lowest xe values of crystalline vanillin were observed in pure water (1.25 103 at T = 298 K) over the entire temperature investigated. The highest solubilities of crystalline vanillin in pure propane-1,2-diol were possibly due to lower polarity of propane-1,2-diol as compared to pure water as reported in literature (Bhat et al., 2014). The influence of mass fraction of propane-1,2-diol on solubility of crystalline vanillin at T = (298–318) K was also evaluated and results of this study are presented in Fig. 2. Fig. 2 showed that the solubility of crystalline vanillin was increasing continuously with increase in mass fraction of propane-1,2-diol in propane-1,2-diol + water
Table 1 Sample table for detailed information about materials used in the experiment. Material
Molecular formula
Molar mass (g mol1)
Purity (mass fraction)
Purification method
Analysis method
Source
Vanillin Propane-1,2-diol Water
C8H8O3 C3H8O2 H2O
152.15 76.09 18.01
0.990 0.995 1.000
None None None
HPLC GC Conductivity < 1 lS cm1
Sigma Aldrich Fluka Chemicals Milli-Q purification unit
HPLC, high performance liquid chromatography; GC, gas chromatography.
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results indicated good correlation of measured solubility data of crystalline vanillin with Van’t Hoff model. 3.3. Correlation of measured solubilities of vanillin with the modified Apelblat model The modified Apelblat model solubility of crystalline vanillin (xApl) can be calculated using Eq. (3) (Apelblat & Manzurola, 1999):
ln xApl ¼ A þ
Fig. 2. Influence of mass fraction of propane-1,2-diol (m) on mole fraction solubility (ln xe) of crystalline vanillin at T = (298–318) K; 298 K, 303 K, 308 K, 313 K and 318 K.
cosolvent mixtures over the entire temperature range investigated. These results were in good agreement with previously published solubility data of isoniazid analog in propane-1,2-diol + water cosolvent mixtures at T = (298–338) K and p = 0.1 MPa (Bhat et al., 2014). Based on solubility data of this work, crystalline vanillin has been considered as soluble in water and freely soluble in propane-1,2-diol (Shakeel, Haq, & Siddiqui, 2015). In this work, propane-1,2-diol was able to enhance the solubility of crystalline vanillin sufficiently in water, hence it can be used as a physiologically compatible cosolvent in formulation development of vanillin in food and pharmaceutical industries. 3.2. Correlation of measured solubilities of vanillin with Van’t Hoff model The Van’t Hoff model solubility of crystalline vanillin (ln xVan’t) at temperature (T/K) in various propane-1,2-diol + water cosolvent mixtures can be calculated using Eq. (1) (Shakeel, Haq, Alanazi, et al., 2015):
ln xVan’t ¼ a þ
b T
ð1Þ
In which, the symbols a and b are the Van’t Hoff model parameters which were determined by plotting ln xe values of crystalline vanillin against 1/T. The correlation of measured solubitities of crystalline vanillin (xe) with this model (xVan’t) was evaluated by calculating the values of root mean square deviations (RMSD) using Eq. (2).
"
2 #12 N Van’t 1X x xe RMSD ¼ N i¼1 xe
B þ C lnðTÞ T
ð3Þ
In which, the coefficients A, B and C are the modified Apelblat model parameters. These parameters were determined by multivariate regression analysis of experimental solubilities of crystalline vanillin (Shakeel, Haq, & Siddiqui, 2015; Shakeel, Haq, Alanazi, et al., 2015). The graphical correlations between xe and xApl values of crystalline vanillin in various propane-1,2-diol + water cosolvent mixtures are presented in Fig. S4. The resulting data of this correlation are presented in Table S2. The values of RMSD and R2 in various propane-1,2-diol + water cosolvent mixtures were recorded as (0.14–0.98)% and 0.9968– 0.9999 which showed good correlation of experimental solubility data of crystalline vanillin with the modified Apelblat model. 3.4. Correlation of measured solubilities of vanillin with Yalkowsky model The logarithmic Yalkowsky model solubility of crystalline vanillin (log xYal) in various propane-1,2-diol + water cosolvent mixtures can be calculated using Eq. (4) (Yalkowsky & Roseman, 1981):
Log xYal ¼ m1 log S1 þ m2 log S2
ð4Þ
In which, S1 and S2 are the mole fraction solubilities of crystalline vanillin in pure solvent 1 (propane-1,2-diol) and pure solvent 2 (water), respectively; and m1 and m2 are the mass fractions of propane-1,2-diol and water in the absence of solute/vanillin, respectively. The resulting data of this correlation are presented in Table S3. The RMSD values in various propane-1,2-diol + water cosolvent mixtures were recorded as (0.82–4.69)% which indicated again good correlation of measured solubility data of crystalline vanillin with Yalkowsky model. 3.5. Thermodynamic parameters for vanillin dissolution Thermodynamic parameters of solute in cosolvent mixtures are useful in evaluation of dissolution behavior of solute. Hence, in this work, the DsolH0 values for dissolution behavior of crystalline vanillin in various propane-1,2-diol + water cosolvent mixtures were determined directly by Van’t Hoff analysis using Eq. (5) (Holguín, Rodríguez, Cristancho, Delgado, & Martínez, 2012; Ruidiaz, Delgado, Martínez, & Marcus, 2010):
0 ð2Þ
1 @ ln x D H0 @ A ¼ sol R @ 1T T 1 hm
In which, N is the number of experimental data points which were five in this work. The graphical correlations between xe and xVan’t values of crystalline vanillin in various propane-1,2-diol + water cosolvent mixtures are presented in Fig. S3. The resulting data of this correlation are presented in Table S1. The values of RMSD and correlation coefficients (R2) in various propane-1,2-diol + water cosolvent mixtures were recorded as (0.46–1.32)% and 0.9960–0.9996, respectively (Table S1). These
ð5Þ
P
In which, R is the universal gas constant which is equal to 8.314 J mol1 K1. Thm is the mean harmonic temperature which was 307.98 K in this work. According to Eq. (5), the graphs were plotted between ln xe values of crystalline vanillin and 1T T 1 hm
(Fig. S5). The Van’t Hoff plots of vanillin in all propane-1,2-diol + water cosolvent mixtures were observed linear with R2 values in the range of 0.9960–0.9990.
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The DsolG0 values for vanillin dissolution in various propane1,2-diol + water cosolvent mixtures were determined at Thm by Krug analysis approach using Eq. (6) (Krug, Hunter, & Grieger, 1976):
Dsol G0 ¼ RT hm intercept
ð6Þ
In which, the intercept values for each cosolvent mixture were determined from Fig. S5. The DsolS0 values for vanillin dissolution in various propane-1,2diol + water cosolvent mixtures were calculated using Eq. (7):
Dsol S0 ¼
Dsol H0 Dsol G0 T hm
ð7Þ
The results of thermodynamic analysis for vanillin dissolution in various propane-1,2-diol + water cosolvent mixtures are presented in Table 3. The DsolH0 values for vanillin dissolution in various propane1,2-diol + water cosolvent mixtures were found to be positive values in the range of (7.69–28.69) kJ mol1. The DsolH0 value for dissolution behavior of crystalline vanillin was observed highest in pure water (28.69 kJ mol1) and lowest in pure propane-1,2-diol (7.69 kJ mol1). The DsolG0 values for vanillin dissolution were also recorded as positive values in the range of (6.52–16.12) kJ mol1. The DsolG0 value for dissolution behavior of crystalline vanillin was also observed highest in pure water (16.12 kJ mol1) and lowest in pure propane-1,2-diol (6.52 kJ mol1). The DsolH0 and DsolG0 values for vanillin dissolution were found to be decreasing with increase in mass fraction of propane-1,2-diol in propane-1, 2-diol + water cosolvent mixtures. These results were in accordance with the solubility data of crystalline vanillin in all
propane-1,2-diol + water cosolvent mixtures. Based on positive values of DsolH0 and DsolG0, the dissolution behavior of crystalline vanillin was considered as an endothermic and spontaneous in all propane-1,2-diol + water cosolvent mixtures. The DsolS0 values for vanillin dissolution were also recorded as positive values in the range of (3.80–40.80) J mol1 K1. The positive values of DsolS0 indicated an entropy-driven dissolution behavior of crystalline vanillin in all propane-1,2-diol + water cosolvent mixtures. Overall, the dissolution behavior of crystalline vanillin was observed as an endothermic, spontaneous and an entropy driven in all propane-1,2-diol + water cosolvent mixtures that was probably due to the stronger molecular interactions between vanillin and solvent molecules (Shakeel, Haq, & Siddiqui, 2015; Shakeel, Haq, Alanazi, et al., 2015).
3.6. Solvation behavior of vanillin solution via enthalpy–entropy compensation analysis In the current work, the solvation mechanism of crystalline vanillin in various propane-1,2-diol + water cosolvent mixtures was evaluated by an enthalpy–entropy compensation analysis as reported in literature (Bustamante, Romero, & Reillo, 1995; Ruidiaz et al., 2010). For this purpose, the weighted plots of DsolH0 were constructed as a function of DsolG0 at mean harmonic temperature. This analysis permits the observation of similar mechanism for solvation behavior/mechanism of solutes in cosolvent mixtures as per tendencies obtained (Tomlinson, 1983). The results of DsolH0 vs. DsolG0 plot for solvation mechanism of crystalline vanillin in various propane-1,2-diol + water cosolvent mixtures are presented in Fig. 3. It was observed that crystalline
Table 3 Thermodynamic parameters and R2 values for dissolution of crystalline vanillin in various propane-1,2-diol + water cosolvent mixtures (m) at mean harmonic temperature of 307.98 K. Parameters
m = 0.0
m = 0.1
m = 0.2
m = 0.3
m = 0.4
m = 0.5
m = 0.6
m = 0.7
m = 0.8
m = 0.9
m = 1.0
DsolH0/kJ mol1 DsolG0/kJ mol1 DsolS0/J mol1.K1 R2
28.69 16.12 40.80 0.997
26.14 15.14 35.73 0.998
23.08 14.19 27.99 0.999
22.73 13.24 30.83 0.997
21.79 12.22 31.09 0.996
20.77 11.21 31.04 0.996
17.81 10.28 24.44 0.997
14.22 9.37 15.74 0.999
13.65 8.40 17.06 0.996
9.66 7.46 7.15 0.997
7.69 6.52 3.80 0.996
Fig. 3. DsolH0 versus DsolG0 enthalpy–entropy compensation curve for solvation/dissolution behavior of crystalline vanillin in various propane-1,2-diol + water cosolvent mixtures at mean harmonic temperature of 307.98 K.
F. Shakeel et al. / Food Chemistry 188 (2015) 57–61
vanillin in all propane-1,2-diol + water cosolvent mixtures presents nonlinear DsolH0 vs. DsolG0 plot with a positive slope value which was greater than unity. Therefore, the driving mechanism for solvation mechanism of crystalline vanillin was proposed as an enthalpy-driven in all propane-1,2-diol + water cosolvent mixtures. This indicated better solvation of crystalline vanillin in propane-1,2-diol molecules (Ahumada, Delgado, & Martínez, 2012). 4. Conclusion The solubilities of commonly used flavoring agent vanillin in various propane-1,2-diol + water cosolvent mixtures were measured at T = (298–318) K and p = 0.1 MPa using an isothermal method. The solubilities of crystalline vanillin were found to be increased continuously with increase in temperature and mass fraction of propane-1,2-diol in propane-1,2-diol + water cosolvent mixtures. The measured solubility data of vanillin were correlated well with calculated ones. Van’t Hoff and Krug analysis indicated an endothermic, spontaneous and an entropy-driven dissolution of crystalline vanillin in all propane-1,2-diol + water cosolvent mixtures. Based on these results, crystalline vanillin has been considered as soluble in water and freely soluble in propane-1,2-diol. Due to freely soluble nature of crystalline vanillin in propane-1, 2-diol, it could be applied as a physiologically compatible cosolvent in formulation development of vanillin in food and pharmaceutical industries. Conflict of interest The authors report no conflict of interest related with this manuscript. Acknowledgement The project was financially supported by King Saud University, Vice Deanship of Research Chairs, Kayyali Chair for Pharmaceutical Industry (Grant No. FN-2015). Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.foodchem.2015. 04.113. References Ahumada, E. A., Delgado, D. R., & Martínez, F. (2012). Solution thermodynamics of acetaminophen in some PEG 400 + water mixtures. Fluid Phase Equilibria, 332, 120–127. Apelblat, A., & Manzurola, E. (1999). Solubilities of o-acetylsalicylic, 4-aminosalicylic, 3,5-dinitrosalicylic and p-toluic acid and magnesium-DL-aspartate in water from T = (278 to 348) K. The Journal of Chemical Thermodynamics, 31, 85–91.
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Bhat, M. A., Haq, N., & Shakeel, F. (2014). Solubility and dissolution thermodynamics of N-(4-chlorophenyl)-2-(pyridin-4-ylcarbonyl) hydrazinecarbothioamide in PG + water co-solvent mixtures at (298.15 to 338.15) K. Thermochimica Acta, 593, 37–42. Bustamante, P., Romero, S., & Reillo, A. (1995). Thermodynamics of paracetamol in amphiprotic and amphiprotic-aprotic solvent mixtures. Pharmaceutical Sciences, 1, 505–507. Delgado, D. R., Pena, M. A., & Martinez, F. (2014). Preferential solvation of some sulfonamides in propylene glycol + water solvent according to the KIBI and QLQC methods. Journal of Solution Chemistry, 43, 360–374. Higuchi, T., & Connors, K. A. (1965). Phase-solubility techniques. Advanced Analytical Chemistry and Instrumentation, 4, 117–122. Holguín, A. R., Rodríguez, G. A., Cristancho, D. M., Delgado, D. R., & Martínez, F. (2012). Solution thermodynamics of indomethacin in propylene glycol + water mixtures. Fluid Phase Equilibria, 314, 134–139. Kayaci, F., & Uyar, T. (2012). Encapsulation of vanillin/cyclodextrin inclusion complex in electrospun polyvinyl alcohol (PVA) nanowebs: Prolonged shelf-life and high temperature stability of vanillin. Food Chemistry, 133, 641–649. Krug, R. R., Hunter, W. G., & Grieger, R. A. (1976). Enthalpy-entropy compensation. 2. Separation of the chemical from the statistic effect. Journal of Physical Chemistry, 80, 2341–2351. Kumar, R., Sharma, P. K., & Mishra, P. S. (2012). A review on the vanillin derivatives showing various biological activities. International Journal of Pharm Tech Research, 4, 266–279. Manzurola, E., & Apelblat, A. (2002). Solubilities of L-glutamic acid, 3-nitrobenzoic acid, acetylsalicylic, p-toluic acid, calcium-L-lactate, calcium gluconate, magnesium-DL-aspartate, and magnesium-L-lactate in water. The Journal of Chemical Thermodynamics, 34, 1127–1136. Munoz, M. D. M., Delgado, D. R., Pena, M. A., Jouyban, A., & Martinez, F. (2015). Solubility and preferential solvation of sulfadiazine, sulfamerazine and sulfamethazine in propylene glycol + water mixtures at 298.15 K. Journal of Molecular Liquids, 204, 132–136. Noubigh, A., Cherif, M., Provost, E., & Abderrabba, M. (2008). Solubility of gallic acid, vanillin, syringic acid and protocatechuic acid in aqueous sulfate solutions from (293.15 to 318.15) K. Journal of Chemical & Engineering Data, 53, 1675–1678. Peng, H., Xiong, H., Li, J., Xie, M., Liu, Y., Bai, C., et al. (2010). Vanillin cross-linked chitosan microspheres for controlled release of resveratrol. Food Chemistry, 121, 23–28. Ruidiaz, M. A., Delgado, D. R., Martínez, F., & Marcus, Y. (2010). Solubility and preferential solvation of indomethacin in 1,4-dioxane + water solvent mixtures. Fluid Phase Equilibria, 299, 259–265. Shakeel, F., & Anwer, M. K. (2015). Dissolution thermodynamics and solubility of silymarin in PEG 400-water mixtures at different temperatures. Drug Development and Industrial Pharmacy. http://dx.doi.org/10.3109/03639045. 2015.1009914. Shakeel, F., Haq, N., Alanazi, F. K., & Alsarra, I. A. (2015). Thermodynamics of solubility of isatin in (PEG 400 + water) mixed solvent systems at T = (298.15 to 338.15) K. The Journal of Chemical Thermodynamics, 82, 156–160. Shakeel, F., Haq, N., & Siddiqui, N. A. (2015). Solubility and thermodynamics function of vanillin in ten different environmentally benign solvents. Food Chemistry, 180, 244–248. Shakeel, F., Haq, N., Siddiqui, N. A., Alanazi, F. K., & Alsarra, I. A. (2015). Thermodynamics of the solubility of reserpine in {2-(2-ethoxyethoxy) ethanol + water} mixed solvent systems at different temperatures. The Journal of Chemical Thermodynamics, 85, 57–60. Tomlinson, E. (1983). Enthalpy-entropy compensation analysis of pharmaceutical, biochemical and biological systems. International Journal of Pharmaceutics, 13, 115–144. Yalkowsky, S. H., & Roseman, T. J. (1981). Solubilization of drugs by cosolvents. In S. H. Yalkowsky (Ed.), Techniques of solubilization of drugs (pp. 91–134). New York: Marcel Dekker Inc. Zeng, A. D., Pang, X. L., Wu, N., Wang, D., Nan, G. J., Yang, G. D., et al. (2014). Solubility of daidzein in propylene glycol + water cosolvent mixtures. Fluid Phase Equilibria, 366, 127–133.
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Food Chemistry journal homepage: www.elsevier.com/locate/foodchem
Solubility and thermodynamic behavior of vanillin in propane-1, 2-diol + water cosolvent mixtures at different temperatures Faiyaz Shakeel a,b,⇑, Nazrul Haq a,b, Nasir A. Siddiqui c, Fars K. Alanazi b, Ibrahim A. Alsarra a,b a
Center of Excellence in Biotechnology Research, College of Science, King Saud University, P.O. Box 2460, Riyadh 11451, Saudi Arabia Kayyali Chair for Pharmaceutical Industry, Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia c Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia b
a r t i c l e
i n f o
Article history: Received 2 March 2015 Received in revised form 24 April 2015 Accepted 27 April 2015 Available online 27 April 2015 Keywords: Cosolvent mixture Mathematical models Propane-1,2-diol Solubility Thermodynamics Vanillin
a b s t r a c t The solubilities of bioactive compound vanillin were measured in various propane-1,2-diol + water cosolvent mixtures at T = (298–318) K and p = 0.1 MPa. The experimental solubility of crystalline vanillin was determined and correlated with calculated solubility. The results showed good correlation of experimental solubilities of crystalline vanillin with calculated ones. The mole fraction solubility of crystalline vanillin was recorded highest in pure propane-1,2-diol (7.06 102 at 298 K) and lowest in pure water (1.25 103 at 298 K) over the entire temperature range investigated. Thermodynamic behavior of vanillin in various propane-1,2-diol + water cosolvent mixtures was evaluated by Van’t Hoff and Krug analysis. The results showed an endothermic, spontaneous and an entropy-driven dissolution of crystalline vanillin in all propane-1,2-diol + water cosolvent mixtures. Based on solubility data of this work, vanillin has been considered as soluble in water and freely soluble in propane-1,2-diol. Ó 2015 Elsevier Ltd. All rights reserved.
1. Introduction Vanillin is a phenolic aldehyde (Fig. 1) which is available commercially as a white to slightly yellow crystalline powder (Noubigh, Cherif, Provost, & Abderrabba, 2008). It is commonly used flavoring agent which is obtained from the bean or pod of Vanilla orchid (Kumar, Sharma, & Mishra, 2012). Therapeutically, it has been investigated as antioxidant, antimicrobial and antimutagenic although clinical trials are lacking (Kayaci & Uyar, 2012; Kumar et al., 2012; Peng et al., 2010). The strong antioxidant activity of vanillin is mainly due to the presence of phenolic compounds (Shakeel, Haq, & Siddiqui, 2015). It has been reported as soluble in water and freely soluble in propane-1,2-diol at 298 K (Noubigh et al., 2008; Shakeel, Haq, & Siddiqui, 2015). The solubility of bioactive compounds in cosolvent mixtures is one of the most important physicochemical parameter which is useful in purification, crystallization, preformulation studies and formulation development of these bioactive compounds (Shakeel & Anwer, 2015; Shakeel, Haq, Alanazi, & Alsarra, 2015; Shakeel, Haq, Siddiqui, Alanazi, & Alsarra, 2015). Propane-1,2-diol [also known as propylene glycol (PG)] is one of the commonly used cosolvent for solubilization ⇑ Corresponding author at: Center of Excellence in Biotechnology Research, College of Science, King Saud University, P.O. Box 2460, Riyadh 11451, Saudi Arabia. E-mail address: [email protected] (F. Shakeel). http://dx.doi.org/10.1016/j.foodchem.2015.04.113 0308-8146/Ó 2015 Elsevier Ltd. All rights reserved.
and stabilization of drugs in an aqueous media (Bhat, Haq, & Shakeel, 2014; Delgado, Pena, & Martinez, 2014; Munoz, Delgado, Pena, Jouyban, & Martinez, 2015; Zeng et al., 2014). Various mathematical models have been developed to evaluate the influence of temperature on solubility of solute but the modified Apelblat and Van’t Hoff models are the commonly used models for this purpose (Apelblat & Manzurola, 1999; Manzurola & Apelblat, 2002; Shakeel, Haq, & Siddiqui, 2015). However, the log-linear model of Yalkowsky is commonly used model to evaluate the influence of cosolvent mixture on solubility of solute (Yalkowsky & Roseman, 1981). The temperature dependent solubilities of crystalline vanillin in various propane-1,2-diol + water cosolvent mixtures are not available in literature. Therefore, in this work, the solubilities of bioactive compound vanillin in various propane-1,2-diol + water cosolvent mixtures were measured and correlated at T = (298–318) K and p = 0.1 MPa using an isothermal method reported by Higuchi & Connors (1965). From the solubility data of vanillin, various thermodynamic parameters such as standard dissolution enthalpy (DsolH0), standard dissolution entropy (DsolS0) and standard Gibbs free energy (DsolG0) for vanillin dissolution were also determined. The solubility data of this work could be useful in preformulation studies and formulation development of vanillin due to freely soluble nature of vanillin in propane-1,2-diol.
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F. Shakeel et al. / Food Chemistry 188 (2015) 57–61 Table 2 Experimental mole fraction solubilities (xe) of crystalline vanillin against mass fraction of propane-1,2-diol (m) in various propane-1,2-diol + water cosolvent mixtures at temperatures T = (298–318) K and pressure p = 0.1 MPa.a m
xe
0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
Fig. 1. Chemical structure of crystalline vanillin.
2. Experimental
T = 298 K
T = 303 K
T = 308 K
T = 313 K
T = 318 K
1.25 103 1.91 103 2.88 103 4.22 103 6.32 103 9.45 103 1.42 102 2.13 102 3.12 102 4.75 102 7.06 102
1.55 103 2.31 103 3.40 103 4.89 103 7.39 103 1.11 102 1.61 102 2.36 102 3.46 102 5.13 102 7.49 102
1.89 103 2.76 103 3.94 103 5.80 103 8.62 103 1.27 102 1.82 102 2.59 102 3.80 102 5.44 102 7.79 102
2.22 103 3.19 103 4.52 103 6.50 103 9.84 103 1.44 102 2.03 102 2.82 102 4.11 102 5.74 102 8.17 102
2.60 103 3.72 103 5.20 103 7.53 103 1.09 102 1.60 102 2.22 102 3.06 102 4.41 102 6.11 102 8.63 102
a The standard uncertainties u are u(T) = 0.16 K, ur(m) = 0.1%, u(p) = 0.003 MPa and ur(xe) = 1.35%.
2.1. Materials Vanillin was obtained from Sigma Aldrich (St. Louis, MO). Propane-1,2-diol was obtained from Fluka Chemicals (Busch, Switzerland). High performance liquid chromatographic (HPLC) grade acetonitrile and acetone were obtained from Acros Organics (Hamilton, NJ). HPLC grade water was obtained from Milli-Q water purification unit (Berlin, Germany). All the materials used in this work were of high purity (Table 1). 2.2. Measurement of vanillin solubility The mole fraction solubility of crystalline vanillin against mass fraction of propane-1,2-diol (m) in various propane-1,2-diol + water cosolvent mixtures at T = (298–318) K at p = 0.1 MPa was determined using an isothermal method (Higuchi & Connors, 1965). The excess amount of solute was added in known amounts of propane-1,2-diol + water cosolvent mixtures in triplicates. All the samples were vortex mixed for 5 min and transferred to biological shaker (Julabo, PA) for continuous shaking at 100 rpm for 72 h to reach equilibrium. The time period of 72 h was enough to reach equilibrium as reported previously (Shakeel, Haq, & Siddiqui, 2015). The remaining procedure was adopted from previous article (Shakeel, Haq, & Siddiqui, 2015). The quantification of vanillin in solubility samples was carried out by reversed phase HPLC method at the wavelength of 220 nm using ternary mixture of acetonitrile:water:acetone (7:2:1% v/v) as a mobile phase at flow rate of 1.0 mL min1 (Shakeel, Haq, & Siddiqui, 2015). The experimental solubilities (xe) of vanillin in various propane-1, 2-diol + water cosolvent mixtures were calculated as reported in literature (Shakeel, Haq, & Siddiqui, 2015). 3. Results and discussion 3.1. Measured solubility data of vanillin The measured solubility data of crystalline vanillin in various propane-1,2-diol + water cosolvent mixtures at T = (298–318) K and p = 0.1 MPa are presented in Table 2. The solubility data and
thermodynamic behavior of vanillin in propane-1,2-diol + water cosolvent mixtures have not been reported in literature. However, it has been reported as soluble in pure water and freely soluble in pure propane-1,2-diol (Shakeel, Haq, & Siddiqui, 2015). The mole fraction solubility of crystalline vanillin in pure water at T = 298 K has been reported as 1.17 103 and 1.22 103 by Noubigh et al. (2008) and Shakeel, Haq, and Siddiqui (2015), respectively (Noubigh et al., 2008; Shakeel, Haq, & Siddiqui, 2015). However, the mole fraction solubility of crystalline vanillin in pure propane-1,2-diol at T = 298 K has been reported as 7.15 102 (Shakeel, Haq, & Siddiqui, 2015). In this work, the mole fraction solubility of crystalline vanillin in pure water and pure propane-1,2-diol at T = 298 K was recorded as 1.25 103 and 7.06 102, respectively. The experimental solubilities of vanillin were in good agreement with literature solubilities of vanillin in water and propane-1,2-diol at T = 298 K. The graphical correlation between experimental and literature solubilities of vanillin in water and propane-1,2-diol at T = (298–318) K and p = 0.1 MPa are also presented in Figs. S1 and S2, respectively. The results showed good correlation of experimental solubilities of vanillin in water and propane-1,2-diol over the entire temperature range investigated. In general, the xe values of crystalline vanillin were found to be increasing with increase in temperature and mass fraction of propane-1,2-diol in propane-1,2-diol + water cosolvent mixtures over the entire temperature range investigated. The xe values of crystalline vanillin were observed highest in pure propane-1,2-diol (7.06 102 at T = 298 K) over the entire temperature range investigated. However, the lowest xe values of crystalline vanillin were observed in pure water (1.25 103 at T = 298 K) over the entire temperature investigated. The highest solubilities of crystalline vanillin in pure propane-1,2-diol were possibly due to lower polarity of propane-1,2-diol as compared to pure water as reported in literature (Bhat et al., 2014). The influence of mass fraction of propane-1,2-diol on solubility of crystalline vanillin at T = (298–318) K was also evaluated and results of this study are presented in Fig. 2. Fig. 2 showed that the solubility of crystalline vanillin was increasing continuously with increase in mass fraction of propane-1,2-diol in propane-1,2-diol + water
Table 1 Sample table for detailed information about materials used in the experiment. Material
Molecular formula
Molar mass (g mol1)
Purity (mass fraction)
Purification method
Analysis method
Source
Vanillin Propane-1,2-diol Water
C8H8O3 C3H8O2 H2O
152.15 76.09 18.01
0.990 0.995 1.000
None None None
HPLC GC Conductivity < 1 lS cm1
Sigma Aldrich Fluka Chemicals Milli-Q purification unit
HPLC, high performance liquid chromatography; GC, gas chromatography.
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results indicated good correlation of measured solubility data of crystalline vanillin with Van’t Hoff model. 3.3. Correlation of measured solubilities of vanillin with the modified Apelblat model The modified Apelblat model solubility of crystalline vanillin (xApl) can be calculated using Eq. (3) (Apelblat & Manzurola, 1999):
ln xApl ¼ A þ
Fig. 2. Influence of mass fraction of propane-1,2-diol (m) on mole fraction solubility (ln xe) of crystalline vanillin at T = (298–318) K; 298 K, 303 K, 308 K, 313 K and 318 K.
cosolvent mixtures over the entire temperature range investigated. These results were in good agreement with previously published solubility data of isoniazid analog in propane-1,2-diol + water cosolvent mixtures at T = (298–338) K and p = 0.1 MPa (Bhat et al., 2014). Based on solubility data of this work, crystalline vanillin has been considered as soluble in water and freely soluble in propane-1,2-diol (Shakeel, Haq, & Siddiqui, 2015). In this work, propane-1,2-diol was able to enhance the solubility of crystalline vanillin sufficiently in water, hence it can be used as a physiologically compatible cosolvent in formulation development of vanillin in food and pharmaceutical industries. 3.2. Correlation of measured solubilities of vanillin with Van’t Hoff model The Van’t Hoff model solubility of crystalline vanillin (ln xVan’t) at temperature (T/K) in various propane-1,2-diol + water cosolvent mixtures can be calculated using Eq. (1) (Shakeel, Haq, Alanazi, et al., 2015):
ln xVan’t ¼ a þ
b T
ð1Þ
In which, the symbols a and b are the Van’t Hoff model parameters which were determined by plotting ln xe values of crystalline vanillin against 1/T. The correlation of measured solubitities of crystalline vanillin (xe) with this model (xVan’t) was evaluated by calculating the values of root mean square deviations (RMSD) using Eq. (2).
"
2 #12 N Van’t 1X x xe RMSD ¼ N i¼1 xe
B þ C lnðTÞ T
ð3Þ
In which, the coefficients A, B and C are the modified Apelblat model parameters. These parameters were determined by multivariate regression analysis of experimental solubilities of crystalline vanillin (Shakeel, Haq, & Siddiqui, 2015; Shakeel, Haq, Alanazi, et al., 2015). The graphical correlations between xe and xApl values of crystalline vanillin in various propane-1,2-diol + water cosolvent mixtures are presented in Fig. S4. The resulting data of this correlation are presented in Table S2. The values of RMSD and R2 in various propane-1,2-diol + water cosolvent mixtures were recorded as (0.14–0.98)% and 0.9968– 0.9999 which showed good correlation of experimental solubility data of crystalline vanillin with the modified Apelblat model. 3.4. Correlation of measured solubilities of vanillin with Yalkowsky model The logarithmic Yalkowsky model solubility of crystalline vanillin (log xYal) in various propane-1,2-diol + water cosolvent mixtures can be calculated using Eq. (4) (Yalkowsky & Roseman, 1981):
Log xYal ¼ m1 log S1 þ m2 log S2
ð4Þ
In which, S1 and S2 are the mole fraction solubilities of crystalline vanillin in pure solvent 1 (propane-1,2-diol) and pure solvent 2 (water), respectively; and m1 and m2 are the mass fractions of propane-1,2-diol and water in the absence of solute/vanillin, respectively. The resulting data of this correlation are presented in Table S3. The RMSD values in various propane-1,2-diol + water cosolvent mixtures were recorded as (0.82–4.69)% which indicated again good correlation of measured solubility data of crystalline vanillin with Yalkowsky model. 3.5. Thermodynamic parameters for vanillin dissolution Thermodynamic parameters of solute in cosolvent mixtures are useful in evaluation of dissolution behavior of solute. Hence, in this work, the DsolH0 values for dissolution behavior of crystalline vanillin in various propane-1,2-diol + water cosolvent mixtures were determined directly by Van’t Hoff analysis using Eq. (5) (Holguín, Rodríguez, Cristancho, Delgado, & Martínez, 2012; Ruidiaz, Delgado, Martínez, & Marcus, 2010):
0 ð2Þ
1 @ ln x D H0 @ A ¼ sol R @ 1T T 1 hm
In which, N is the number of experimental data points which were five in this work. The graphical correlations between xe and xVan’t values of crystalline vanillin in various propane-1,2-diol + water cosolvent mixtures are presented in Fig. S3. The resulting data of this correlation are presented in Table S1. The values of RMSD and correlation coefficients (R2) in various propane-1,2-diol + water cosolvent mixtures were recorded as (0.46–1.32)% and 0.9960–0.9996, respectively (Table S1). These
ð5Þ
P
In which, R is the universal gas constant which is equal to 8.314 J mol1 K1. Thm is the mean harmonic temperature which was 307.98 K in this work. According to Eq. (5), the graphs were plotted between ln xe values of crystalline vanillin and 1T T 1 hm
(Fig. S5). The Van’t Hoff plots of vanillin in all propane-1,2-diol + water cosolvent mixtures were observed linear with R2 values in the range of 0.9960–0.9990.
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The DsolG0 values for vanillin dissolution in various propane1,2-diol + water cosolvent mixtures were determined at Thm by Krug analysis approach using Eq. (6) (Krug, Hunter, & Grieger, 1976):
Dsol G0 ¼ RT hm intercept
ð6Þ
In which, the intercept values for each cosolvent mixture were determined from Fig. S5. The DsolS0 values for vanillin dissolution in various propane-1,2diol + water cosolvent mixtures were calculated using Eq. (7):
Dsol S0 ¼
Dsol H0 Dsol G0 T hm
ð7Þ
The results of thermodynamic analysis for vanillin dissolution in various propane-1,2-diol + water cosolvent mixtures are presented in Table 3. The DsolH0 values for vanillin dissolution in various propane1,2-diol + water cosolvent mixtures were found to be positive values in the range of (7.69–28.69) kJ mol1. The DsolH0 value for dissolution behavior of crystalline vanillin was observed highest in pure water (28.69 kJ mol1) and lowest in pure propane-1,2-diol (7.69 kJ mol1). The DsolG0 values for vanillin dissolution were also recorded as positive values in the range of (6.52–16.12) kJ mol1. The DsolG0 value for dissolution behavior of crystalline vanillin was also observed highest in pure water (16.12 kJ mol1) and lowest in pure propane-1,2-diol (6.52 kJ mol1). The DsolH0 and DsolG0 values for vanillin dissolution were found to be decreasing with increase in mass fraction of propane-1,2-diol in propane-1, 2-diol + water cosolvent mixtures. These results were in accordance with the solubility data of crystalline vanillin in all
propane-1,2-diol + water cosolvent mixtures. Based on positive values of DsolH0 and DsolG0, the dissolution behavior of crystalline vanillin was considered as an endothermic and spontaneous in all propane-1,2-diol + water cosolvent mixtures. The DsolS0 values for vanillin dissolution were also recorded as positive values in the range of (3.80–40.80) J mol1 K1. The positive values of DsolS0 indicated an entropy-driven dissolution behavior of crystalline vanillin in all propane-1,2-diol + water cosolvent mixtures. Overall, the dissolution behavior of crystalline vanillin was observed as an endothermic, spontaneous and an entropy driven in all propane-1,2-diol + water cosolvent mixtures that was probably due to the stronger molecular interactions between vanillin and solvent molecules (Shakeel, Haq, & Siddiqui, 2015; Shakeel, Haq, Alanazi, et al., 2015).
3.6. Solvation behavior of vanillin solution via enthalpy–entropy compensation analysis In the current work, the solvation mechanism of crystalline vanillin in various propane-1,2-diol + water cosolvent mixtures was evaluated by an enthalpy–entropy compensation analysis as reported in literature (Bustamante, Romero, & Reillo, 1995; Ruidiaz et al., 2010). For this purpose, the weighted plots of DsolH0 were constructed as a function of DsolG0 at mean harmonic temperature. This analysis permits the observation of similar mechanism for solvation behavior/mechanism of solutes in cosolvent mixtures as per tendencies obtained (Tomlinson, 1983). The results of DsolH0 vs. DsolG0 plot for solvation mechanism of crystalline vanillin in various propane-1,2-diol + water cosolvent mixtures are presented in Fig. 3. It was observed that crystalline
Table 3 Thermodynamic parameters and R2 values for dissolution of crystalline vanillin in various propane-1,2-diol + water cosolvent mixtures (m) at mean harmonic temperature of 307.98 K. Parameters
m = 0.0
m = 0.1
m = 0.2
m = 0.3
m = 0.4
m = 0.5
m = 0.6
m = 0.7
m = 0.8
m = 0.9
m = 1.0
DsolH0/kJ mol1 DsolG0/kJ mol1 DsolS0/J mol1.K1 R2
28.69 16.12 40.80 0.997
26.14 15.14 35.73 0.998
23.08 14.19 27.99 0.999
22.73 13.24 30.83 0.997
21.79 12.22 31.09 0.996
20.77 11.21 31.04 0.996
17.81 10.28 24.44 0.997
14.22 9.37 15.74 0.999
13.65 8.40 17.06 0.996
9.66 7.46 7.15 0.997
7.69 6.52 3.80 0.996
Fig. 3. DsolH0 versus DsolG0 enthalpy–entropy compensation curve for solvation/dissolution behavior of crystalline vanillin in various propane-1,2-diol + water cosolvent mixtures at mean harmonic temperature of 307.98 K.
F. Shakeel et al. / Food Chemistry 188 (2015) 57–61
vanillin in all propane-1,2-diol + water cosolvent mixtures presents nonlinear DsolH0 vs. DsolG0 plot with a positive slope value which was greater than unity. Therefore, the driving mechanism for solvation mechanism of crystalline vanillin was proposed as an enthalpy-driven in all propane-1,2-diol + water cosolvent mixtures. This indicated better solvation of crystalline vanillin in propane-1,2-diol molecules (Ahumada, Delgado, & Martínez, 2012). 4. Conclusion The solubilities of commonly used flavoring agent vanillin in various propane-1,2-diol + water cosolvent mixtures were measured at T = (298–318) K and p = 0.1 MPa using an isothermal method. The solubilities of crystalline vanillin were found to be increased continuously with increase in temperature and mass fraction of propane-1,2-diol in propane-1,2-diol + water cosolvent mixtures. The measured solubility data of vanillin were correlated well with calculated ones. Van’t Hoff and Krug analysis indicated an endothermic, spontaneous and an entropy-driven dissolution of crystalline vanillin in all propane-1,2-diol + water cosolvent mixtures. Based on these results, crystalline vanillin has been considered as soluble in water and freely soluble in propane-1,2-diol. Due to freely soluble nature of crystalline vanillin in propane-1, 2-diol, it could be applied as a physiologically compatible cosolvent in formulation development of vanillin in food and pharmaceutical industries. Conflict of interest The authors report no conflict of interest related with this manuscript. Acknowledgement The project was financially supported by King Saud University, Vice Deanship of Research Chairs, Kayyali Chair for Pharmaceutical Industry (Grant No. FN-2015). Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.foodchem.2015. 04.113. References Ahumada, E. A., Delgado, D. R., & Martínez, F. (2012). Solution thermodynamics of acetaminophen in some PEG 400 + water mixtures. Fluid Phase Equilibria, 332, 120–127. Apelblat, A., & Manzurola, E. (1999). Solubilities of o-acetylsalicylic, 4-aminosalicylic, 3,5-dinitrosalicylic and p-toluic acid and magnesium-DL-aspartate in water from T = (278 to 348) K. The Journal of Chemical Thermodynamics, 31, 85–91.
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Bhat, M. A., Haq, N., & Shakeel, F. (2014). Solubility and dissolution thermodynamics of N-(4-chlorophenyl)-2-(pyridin-4-ylcarbonyl) hydrazinecarbothioamide in PG + water co-solvent mixtures at (298.15 to 338.15) K. Thermochimica Acta, 593, 37–42. Bustamante, P., Romero, S., & Reillo, A. (1995). Thermodynamics of paracetamol in amphiprotic and amphiprotic-aprotic solvent mixtures. Pharmaceutical Sciences, 1, 505–507. Delgado, D. R., Pena, M. A., & Martinez, F. (2014). Preferential solvation of some sulfonamides in propylene glycol + water solvent according to the KIBI and QLQC methods. Journal of Solution Chemistry, 43, 360–374. Higuchi, T., & Connors, K. A. (1965). Phase-solubility techniques. Advanced Analytical Chemistry and Instrumentation, 4, 117–122. Holguín, A. R., Rodríguez, G. A., Cristancho, D. M., Delgado, D. R., & Martínez, F. (2012). Solution thermodynamics of indomethacin in propylene glycol + water mixtures. Fluid Phase Equilibria, 314, 134–139. Kayaci, F., & Uyar, T. (2012). Encapsulation of vanillin/cyclodextrin inclusion complex in electrospun polyvinyl alcohol (PVA) nanowebs: Prolonged shelf-life and high temperature stability of vanillin. Food Chemistry, 133, 641–649. Krug, R. R., Hunter, W. G., & Grieger, R. A. (1976). Enthalpy-entropy compensation. 2. Separation of the chemical from the statistic effect. Journal of Physical Chemistry, 80, 2341–2351. Kumar, R., Sharma, P. K., & Mishra, P. S. (2012). A review on the vanillin derivatives showing various biological activities. International Journal of Pharm Tech Research, 4, 266–279. Manzurola, E., & Apelblat, A. (2002). Solubilities of L-glutamic acid, 3-nitrobenzoic acid, acetylsalicylic, p-toluic acid, calcium-L-lactate, calcium gluconate, magnesium-DL-aspartate, and magnesium-L-lactate in water. The Journal of Chemical Thermodynamics, 34, 1127–1136. Munoz, M. D. M., Delgado, D. R., Pena, M. A., Jouyban, A., & Martinez, F. (2015). Solubility and preferential solvation of sulfadiazine, sulfamerazine and sulfamethazine in propylene glycol + water mixtures at 298.15 K. Journal of Molecular Liquids, 204, 132–136. Noubigh, A., Cherif, M., Provost, E., & Abderrabba, M. (2008). Solubility of gallic acid, vanillin, syringic acid and protocatechuic acid in aqueous sulfate solutions from (293.15 to 318.15) K. Journal of Chemical & Engineering Data, 53, 1675–1678. Peng, H., Xiong, H., Li, J., Xie, M., Liu, Y., Bai, C., et al. (2010). Vanillin cross-linked chitosan microspheres for controlled release of resveratrol. Food Chemistry, 121, 23–28. Ruidiaz, M. A., Delgado, D. R., Martínez, F., & Marcus, Y. (2010). Solubility and preferential solvation of indomethacin in 1,4-dioxane + water solvent mixtures. Fluid Phase Equilibria, 299, 259–265. Shakeel, F., & Anwer, M. K. (2015). Dissolution thermodynamics and solubility of silymarin in PEG 400-water mixtures at different temperatures. Drug Development and Industrial Pharmacy. http://dx.doi.org/10.3109/03639045. 2015.1009914. Shakeel, F., Haq, N., Alanazi, F. K., & Alsarra, I. A. (2015). Thermodynamics of solubility of isatin in (PEG 400 + water) mixed solvent systems at T = (298.15 to 338.15) K. The Journal of Chemical Thermodynamics, 82, 156–160. Shakeel, F., Haq, N., & Siddiqui, N. A. (2015). Solubility and thermodynamics function of vanillin in ten different environmentally benign solvents. Food Chemistry, 180, 244–248. Shakeel, F., Haq, N., Siddiqui, N. A., Alanazi, F. K., & Alsarra, I. A. (2015). Thermodynamics of the solubility of reserpine in {2-(2-ethoxyethoxy) ethanol + water} mixed solvent systems at different temperatures. The Journal of Chemical Thermodynamics, 85, 57–60. Tomlinson, E. (1983). Enthalpy-entropy compensation analysis of pharmaceutical, biochemical and biological systems. International Journal of Pharmaceutics, 13, 115–144. Yalkowsky, S. H., & Roseman, T. J. (1981). Solubilization of drugs by cosolvents. In S. H. Yalkowsky (Ed.), Techniques of solubilization of drugs (pp. 91–134). New York: Marcel Dekker Inc. Zeng, A. D., Pang, X. L., Wu, N., Wang, D., Nan, G. J., Yang, G. D., et al. (2014). Solubility of daidzein in propylene glycol + water cosolvent mixtures. Fluid Phase Equilibria, 366, 127–133.
