Determination of the solubility, dissolution enthalpy and entropy of icariin in water, ethanol, and methanol

doi:10.1016/j.fluid.2012.03.022

Fluid Phase Equilibria

Volume 324, 25 June 2012, Pages 41-43

https://doi.org/10.1016/j.fluid.2012.03.022 Get rights and content

Abstract

The solubility of icariin in water, ethanol, and methanol solutions was measured by UV spectrophotometry from 288.2 K to 328.2 K. The solubility of icariin in the three solvents increased with temperature. Solubility data correlated with a modified Apelblat equation. The enthalpy and entropy of dissolution of icariin were determined using van’t Hoff plots. The polarity indices and the surface tension of solvents affect the solubility behaviour.

Highlights

► The solubility of icariin was measured the first time. ► The solubility of icariin in the three solvents increased with temperature. ► Solubility data correlated with a modified Apelblat equation. ► The viscosity and the surface tension of solvents affect the solubility behaviour.

Introduction

Icariin, a natural flavonoid, was isolated from Epimedium Herba and is considered to be the major bioactive component of Epimedium Herba [1], [2]. The chemical name of this compound is 3-[(6-deoxy-alpha-l-mannopyranosyl)oxy]-7-(beta-d-glucopyranosyloxy)-5-hydroxy-2-(4-methoxyphenyl)-8-(3-methyl-2-buten-1-yl)-4H-1-benzopyran-4-one. Fig. 1 shows the chemical structure of icariin.

Icariin has a broad range of therapeutic applications in cardiovascular, endocrine, bronchial, urinary and immune systems [1], [2]. For pharmaceutical use, icariin is usually extracted from the Epimedium grandiflorum Morr using solvents such as water, alcohols, or mixtures of these, followed by purification and crystallization from the solution. Therefore, it is important to have thermodynamic data for the solubility of icariin in different solvents. However, only equilibrium solubility of icariin and its apparent oil/water partition coefficient have been reported in the literature. Solubility of icariin in different solvents at different temperatures has not been reported until now. So it is necessary to determine systematically the solubility of icariin since the solubility data are important for its extraction and purification. The temperature dependence of the solubility allows a thermodynamic analysis that permits insight into the molecular mechanisms involved in the solution processes [3].

In this work, the solubility of icariin in water, ethanol and methanol from 288.2 K to 328.2 K was measured by ultraviolet spectrophotometry (UV). The enthalpy and entropy of dissolution of icariin were estimated based on regression of the solubility data by utilizing the van’t Hoff equation.

Section snippets

Materials and apparatus

Icariin (C₃₃H₄₀O₁₅, CAS: 489-32-7, purity higher than 0.990 in mass fraction) was purchased from the National Institute for the Control of Pharmaceuticals and Biological Products (Beijing, China). The ethanol and methanol used were of analytical purity grade with mass fraction purity higher than 0.990 and 0.995 respectively and were provided by Tianjin Kermel Chemical Reagent Co., Ltd (Tianjin, China). Redistilled deionized water (conductivity <2 μS cm⁻¹) was used throughout the study. The

Results and discussion

Solubility data for icariin in water, ethanol and methanol at different temperatures are presented in Table 2. The temperature dependence of icariin solubility in solvents can be described by the modified semi-empirical Apelblat equation [6], [7], [8], [9] (2). $ln (x_{1}) = A + \frac{B}{T / K} + C ln (\frac{T}{K})$ where x₁ is the mole solubility of icariin, T is the absolute temperature, and A, B and C are the parameters determined by least square analysis. Calculated solubility values for icariin are provided in Table 2. The

Conclusion

Solubility of icariin in water, ethanol and methanol was measured by UV spectrophotometry from 288.2 K to 328.2 K. The solubility of icariin in the three solvents was a function of temperature, with solubility increasing with temperature. The experimental data were correlated with the modified Apelblat equation. The calculated results show good agreement with the experimental values. Based on the solubility data, the dissolution enthalpy and entropy of icariin were calculated using van’t Hoff

List of symbols

x₁

mole fraction solubility

m₁

mass of the solute

m₂

mass of the solvent

M₁

molar mass of the solute

M₂

molar mass of the solvent

x_i

experimental solubility value

x_{i}^{calc}

calculated solubility value

gas constant

absolute temperature

ΔH_d

enthalpy of dissolution

ΔS_d

entropy of dissolution

ΔG_d

Gibbs energy of solution

correlation coefficient

density of solvent

n_D

refractive index of solvent

Acknowledgement

This research was financially supported in part by National Natural Science Foundations of China (No. 81173024) to Q. Fu.

References (12)

H.P. Ma et al.
J. Ethnopharmacol.
(2011)
H. Nian et al.
Phytomedicine
(2009)
M.A. Ruidiaz et al.
Fluid Phase Equilib.
(2010)
P. Wang et al.
Fluid Phase Equilib.
(2011)
B.S. Liu et al.
Food Chem.
(2011)
A. Apelblat et al.
J. Chem. Thermodyn.
(1999)

There are more references available in the full text version of this article.

Cited by (51)

Comments on “Study on 2-amino-4-chloro-6-methoxypyrimidine in four binary solvent mixtures: Solubility measurement, calculation, preferential solvation and extended Hildebrand solubility parameter approach analysis”
2023, Journal of Molecular Liquids
A polemic is given regarding the apparent Gibbs energies of dissolution reported by Huang and Yao for 2-amino-4-chloro-6-methoxypyrimidine dissolved in four binary aqueous-organic solvent mixtures at the harmonic mean temperature. Our reanalysis of the authors’ experimental mole fraction solubility data yielded positive values, rather than negative values, for the apparent Gibbs energies of dissolution.
Solubility, thermodynamic properties and molecular simulation of tinidazole in fourteen mono-solvents at different temperatures
2022, Journal of Chemical Thermodynamics
The solubility properties of tinidazole (TNZ) in investigated fourteen mono-solvents were further studied at several temperature points (278.15 K ∼ 323.15 K) under 101.2 kPa using the laser monitoring technique. The selected solvents were acetone, methanol, ethanol, 2-methoxyethanol, 2-ethoxyethanol, 2-propoxyethanol, 2-butoxyethanol, methyl acetate, ethyl acetate, n-propyl acetate, n-butyl acetate, NMP, DMF, DMAC, respectively. The order of solubility of tinidazole in fourteen mono-solvents at 298.15 K is: NMP > DMAC > DMF > acetone > 2-methoxyethanol > methylacetate > 2-ethoxyethanol > ethyl acetate > 2-propoxyethanol > n-propyl acetate > 2-butoxyethanol > n-butyl acetate > methanol > ethanol. As shown by the solubility data of TNZ in chosen fourteen mono-solvents in this work, TNZ is more soluble in higher temperature. The KAT-LSER model and molecular dynamics simulation were adopted to probe the influence of solvent effects and solute–solvent interaction on TNZ solubility. The obtained solubility data of TNZ was fitted by (λh equation, NRTL model, NRTL-SAC model, two-Suffix Margules model, and UNIQUAC model). The results indicate that five models can fit the experimental values well, in which the NRTL-SAC model gives the best regression effect. Moreover, the apparent thermodynamic properties (△_solG°, △_solH° and △_solS°) of TNZ in various solvents were calculated by Van’t Hoff equation. In accordance with the analysis and calculation of dissolution, the dissolution process is is entropy-motivated and endothermal.
Solubility, MD simulation, thermodynamic properties and solvent effect of perphenazine (Form I) in eleven neat organic solvents ranged from 278.15 K to 318.15 K
2022, Journal of Molecular Liquids
Perphenazine has rather effective in the treatment of mental illness. In this work, the solid-liquid equilibrium data of perphenazine in eleven organic neat solvents were determined by laser dynamic method under the atmospheric pressure and temperature range of 278.15 K ∼ 318.15 K. The selected solvents were n-propanol, n-butyl alcohol, methyl acetate, ethyl acetate, n-propyl acetate, n-amyl acetate, N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMAC), acetone, 2-methoxyethanol, glycol ether, respectively. From the results, the solubility of perphenazine is all positively correlated with temperature. Separately, we have adopted the KAT-LSER model and molecular dynamics simulation to investigate the influence of solvent effects and solute-solvent interaction on solute solubility. Meanwhile, there were four activity coefficient models being used to correlate the solubility data and Average relative deviation of models are 4.13% (Margules model), 3.94% (NRTL model), 4.49% (NRTL-SAC model) and 3.06% (UNIQUAC model), respectively, all of which do not exceed 5%. It manifests that the four activity coefficient models can fit the experimental values well, in which the UNIQUAC model gives the best regression effect. Moreover, the apparent thermodynamic properties(△_solG°, △_solH° and △_solS°) of perphenazine in various solvents were calculated by Van’t Hoff equation. In accordance with the analysis and calculation of dissolution, the dissolution process is an endothermic entropy-driven process. This research can provide basic data for the crystallization process of perphenazine.
Solubility, solvent effect, molecular simulation and thermodynamic properties of clozapine in twelve pure solvents
2021, Journal of Chemical Thermodynamics
In this article, laser monitoring technology was used to study the solubility of clozapine in 2-methoxyethanol, 2-ethoxyethanol, 2-propoxyethanol, ethanol, n-propanol, n-butanol, n-pentanol, methyl acetate, ethyl acetate, n-propyl acetate, n-butyl acetate, n-pentyl acetate under the pressure of 0.1 MPa (at 278.15 K–323.15 K). Obviously, the mole fraction solubility of clozapine is positively correlated with the increase of experimental temperature. KAT-LSER model was used to study the solvent effect of clozapine solubility in 12 pure solvents. The results show that the interaction of solvent–solute is mainly due to the dipolarity/polarizability and solvent’s self-cohesiveness. The interaction between solute–solvent molecules was analysed by MD simulation, and the results show that the interaction between solute–solvent molecules has an important influence on the solubility of clozapine. Then the solubility data of clozapine were put into five classical thermodynamic models for simulation, namely the λh model, Apleblat model, NRTL model, Margules model and UNIQUAC model. The values calculated by the five solubility models are in good agreement with the measured solubility, it means that the five models have a higher level of simulation accuracy. On the other hand, the apparent thermodynamic properties of clozapine dissolved in solvent were calculated by van’t Hoff equation, the results show that the dissolution process of clozapine in solvents is an endothermic and driven by enthalpy.
Crystallization mechanism of ammonium aluminum sulfate during cooling process
2021, Journal of Crystal Growth
The cooling crystallization of ammonium aluminum sulfate in pure water was investigated. It was found that the MSZW of ammonium aluminum sulfate decreased slightly with the increasing stirring speed and the decreasing cooling rate. Moreover, some important thermodynamic properties of the ammonium aluminum sulfate dissolution, such as standard enthalpy, standard entropy and standard Gibbs free energy were obtained by calculations. The as-obtained crystals were characterized by X-ray diffraction (XRD), particle size analyzer and scanning electron microscopy (SEM). It was noticed that the as-obtained crystals possessed a rhombic shape with a smooth surface and the particle size of crystals increased with the increasing crystallization time.
Solubility, Hansen solubility parameter and thermodynamic properties of etodolac in twelve organic pure solvents at different temperatures
2020, Journal of Molecular Liquids
In this article, the solubility of etodolac in n-propanol, n-butanol, isopropanol, isobutanol, methyl acetate, n-butyl acetate, n-amyl acetate, isobutyl acetate, isoamyl acetate, toluene, acetone at 278.15 K–323.15 K and dichloromethane at 278.15 K–303.15 K under the pressure of 0.1 MPa was studied using a laser monitoring technology. The experimental results show that the solubility of etodolac in all the 12 pure solvents is positively correlated with the temperature. The van't Hoff model, Apelblat model, λh model, NRTL model and UNIQUAC model were used to fit the etodolac solubility data. Through comparison, it was found that the Apelblat model has the smallest average values of ARD (average relative deviation) and RMSD (root-mean square deviation), and the average values of ARD% and 104 RMSD were 0.92% and 5.99, respectively. The result shows that the Apelblat model was more suitable for correlating the solubility data. The order of solubility of etodolac was analyzed by using Hansen solubility parameter, and the solvent effect was studied by calculating the KAT-LSER parameter. Besides, the thermodynamic properties of the solution process of etodolac were calculated and analyzed by the van't Hoff analysis. The results show that the dissolution process of etodolac is endothermic and entropy-driven.

View all citing articles on Scopus

View full text

Determination of the solubility, dissolution enthalpy and entropy of icariin in water, ethanol, and methanol

Abstract

Highlights

Introduction

Section snippets

Materials and apparatus

Results and discussion

Conclusion

List of symbols

Acknowledgement

J. Ethnopharmacol.

Phytomedicine

Fluid Phase Equilib.

Fluid Phase Equilib.

Food Chem.

J. Chem. Thermodyn.