Solubilities of cholesterol and desmosterol in binary solvent mixtures of n-hexane + ethanol

doi:10.1016/j.fluid.2009.08.016

Fluid Phase Equilibria

Volume 287, Issue 1, 25 December 2009, Pages 1-6

https://doi.org/10.1016/j.fluid.2009.08.016 Get rights and content

Abstract

The solubilities of cholesterol and desmosterol in binary solvent mixtures of n-hexane + ethanol at temperatures of 293.2–323.2 K were determined by a static equilibrium method. The solubilities increase with temperature and go through a maximum at a specific solvent composition. The fusion enthalpy Δ_fusH and the melting point T_m, determined by differential scanning calorimeter (DSC), are 28.5 kJ/mol, 421.7 K for cholesterol and 15.9 kJ/mol, 388.2 K for desmosterol, respectively. The solubilities of cholesterol and desmosterol in pure n-hexane or ethanol follow a linear Van’t Hoff relation with temperature. Activity models, such as Wilson, NRTL and UNIQUAC models were used to correlate and predict the solubilities of cholesterol and desmosterol in n-hexane + ethanol mixed solvents. The interaction parameters were expressed as a function of temperature.

Introduction

Cholesterol (CAS Registry No. 57-88-5, MW 386.66) and desmosterol (CAS Registry No. 313-04-2, MW 384.64) are important steroids in biological processes. As a biosynthetic precursor of cholesterol [1], [2], desmosterol has many similar functions as cholesterol in the membrane structure, dynamics and other biophysical functions [3]. Apart from their intrinsic interests, both structurally similar steroids may be considered as starting materials for the synthesis of some physiologically active steroids. Due to the additional double bond on carbon 24, desmosterol is more active in the partial synthesis of certain physiologically active steroids, some of which have become very important in recent years, e.g., 25-hydroxycholesterol and active vitamin D₃ [4]. The solubilities of cholesterol in pure organic solvents have been widely reported [5], [6], [7], [8], [9]. In our previous study, we measured the solubilities of desmosterol in five single organic solvents [10] and found that desmosterol had a larger solubility compared to cholesterol. Since the solubility is quite small in a single solvent, the use of different cosolvents to change solvation properties is a highly versatile and powerful means of improving the solubility of a solute by several orders of magnitude in some cases [11]. Bar et al. [5] found some alcohols could enhance the aqueous solubility of cholesterol. The effects of various macromolecules on increasing the aqueous solubility of cholesterol were examined by Cadwallader and Madan [12]. Furthermore, the enhancement of solubilities of cholesterol in organic binary solvents has also been reported by Weichherz and Marschik [13], but the solubility of desmosterol in mixed solvents have not been reported.

As a continuation of our previous work [10], we measured the solubilities of cholesterol and desmosterol in binary n-hexane + ethanol solvents. An enhancement of the solubilities of the two steroids in mixed solvents was observed. The solubility data were correlated using activity models like Wilson, NRTL and UNIQUAC models.

Section snippets

Materials

Cholesterol, supplied by Zhejiang Garden High Technology Co., Ltd. (China) with 99% purity determined by HPLC, was further recrystallized in methanol. Desmosterol was prepared in the National Laboratory of Secondary Resources Chemical Engineering of Zhejiang University (China). The purity of desmosterol determined by HPLC was better than 98%. After being dried at 333 K for 24 h in a vacuum oven, cholesterol was stored in a desiccator at room temperature and desmosterol was kept in a desiccator at

Theoretical

The solubility behavior of a solute i in mixed solvents varying with the temperature is described as [14] $\ln (\frac{1}{x_{i}^{i d}}) \equiv \ln (\frac{1}{γ_{i} x_{i}}) = \frac{Δ_{fus} H_{i}}{R T_{t, i}} (\frac{T_{t, i}}{T} - 1) - \frac{Δ C_{p, i}}{R} (\frac{T_{t, i}}{T} - 1) + \frac{Δ C_{p, i}}{R} \ln \frac{T_{t, i}}{T}$ where $x_{i}^{i d}$ is the ideal solubility of the solute, γ_i is the activity coefficient of the solute in the liquid phase, x_i is the solubility of the solute in mole fraction, Δ_fusH_i is the molar enthalpy of fusion of the solute at the triple point temperature, T_t,i is the triple point temperature of the solute, ΔC_p,i is the differential

Calorimetric data

The enthalpy of fusion and the melting temperature were determined to be 28.5 kJ/mol and 421.7 K for cholesterol, which was in good agreement with the literature values [19], [20]. They were 15.9 kJ/mol and 388.2 K for desmosterol.

Solubilities of cholesterol and desmosterol

To validate the method of solubility measurement, the solubilities of cholesterol in ethanol at different temperatures were compared to the literature [5] and shown in Fig. 1. Obviously, the experimental data are in good agreement with the literature data.

The solubilities

Conclusions

The solubilities of cholesterol and desmosterol in binary n-hexane + ethanol solvents system at temperatures of 293.2–323.2 K were measured. Raising the temperature increases the solubilities of both sterols. The solubility curves go through a maximum at around x₂ = 0.45. In all the solvent compositions, the solubilities of desmosterol are larger than those of cholesterol. The thermodynamic properties differences of the two structurally similar steroids may partly contribute to the solubility

Acknowledgements

The authors are grateful for the financial supports from the Ministry of Science and Technology of the People's Republic of China (project Nos. 2006BAD27B03 and 2007AA100404), from the National Natural Science Foundation of China (No. 20676112), and from the Zhejiang Provincial Key Science and Technology Program (No. 2006C11196).

References (29)

G. Bleau et al.
Steroids
(1974)
D.S. Lin et al.
J. Lipid Res.
(1993)
E.J. Westover et al.
Steroids
(2006)
U. Domańska et al.
Fluid Phase Equilib.
(1994)
G.L. Flynn et al.
J. Pharm. Sci.
(1979)
H. Viernstein et al.
Int. J. Pharm.
(2003)
N. Garti et al.
Thermochim. Acta
(1980)
A. Jouyban et al.
Fluid Phase Equilib.
(2003)
M. Umadevi et al.
Spectrochim. Acta A
(2007)
F.Y. Zhang et al.
Spectrochim. Acta A
(2008)

N. Asprion et al.

Fluid Phase Equilib.

(2001)

A. Yokozeki et al.

Appl. Energy

(2007)

S.H. Ali et al.

Fluid Phase Equilib.

(2005)

A. Wechsler et al.

Science

(2003)

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Solubilities of cholesterol and desmosterol in binary solvent mixtures of n-hexane + ethanol

Abstract

Introduction

Section snippets

Materials

Theoretical

Calorimetric data

Solubilities of cholesterol and desmosterol

Conclusions

Acknowledgements

Steroids

J. Lipid Res.

Steroids

Fluid Phase Equilib.

J. Pharm. Sci.

Int. J. Pharm.

Thermochim. Acta

Fluid Phase Equilib.

Spectrochim. Acta A

Spectrochim. Acta A

Fluid Phase Equilib.

Appl. Energy

Fluid Phase Equilib.

Science