Elsevier

Fluid Phase Equilibria

Volume 406, 25 November 2015, Pages 21-26
Fluid Phase Equilibria

Thermodynamic models for determination of the solubility of omeprazole sulfide in (ethanol + ethyl acetate) binary solvent mixtures

https://doi.org/10.1016/j.fluid.2015.07.038Get rights and content

Highlights

  • The solubility of omeprazole sulfide in binary solvent mixtures was investigated.

  • The modified Redlich–Kister (CNIBS/R–K) equation describes the solubility well.

  • The solution process was endothermic and enthalpy-driving process.

Abstract

The solubility of omeprazole sulfide in (ethanol + ethyl acetate) binary solvent mixtures was measured within the temperature range from 277.65 to 333.15 K. The experimental data were fitted using CNIBS/R–K equation and the Jouyban–Acree equation, respectively. All the two equations were proven to give good representations of the experimental values. Computational results showed that the CNIBS/R–K equation was superior to the other equation. The thermodynamic properties of the solution process, including the Gibbs free energy, enthalpy and entropy, were calculated by the van’t Hoff analysis. The values of both the enthalpy change and the standard molar Gibbs free energy change of solution were positive, which indicated that the process was endothermic.

Introduction

Omeprazole sulfide, an amorphous colorless or white powder, is odorless and stable in air generally. Omeprazole sulfide (C17H19N3O2S, FW329.42 g/mol, CAS Registry No. 73590-85-9, structure shown in Fig. 1) is important raw material for the synthesis of omeprazole. The synthetic route of omeprazole sulfide has shown in Fig. 2. AHR is aryl hydrocarbon receptor, which is a mediated transactivation receptor type transcription factor. Omeprazole sulfide has been reported to be an antagonist for AHR in HepG2 cells [1] and it acts as an agonist for AHR in human hepatocytes [2]. It is also a very important intermediate in pharmaceuticals. It is used to synthesize omeprazole and esomeprazole, which are used in the treatment of gastric acid related disorders [3], [4], [5] and are effective in the control of gastric acidity of patients with Zollinger–Ellison syndrome, as well as in patients who do not respond well to histamine H2 receptor antagonists [3], [6]. In addition, gastrointestinal (GI) diseases account for substantial morbidity, mortality, and cost [7], which lead to the increased demand for the related drugs, such as omeprazole Enteric coated tablets, omeprazole capsules, esomeprazole sodium for injection, and esomeprazole magnesium enteric coated tablets. It leads to great demand for this key intermediate. It should be purified by dissolution, crystallization and separation. Crystallization processes are the critical steps which determine the quality of the product [8] of omeprazole sulfide to provide high purity for the next reaction. So it is very important to know the solubility of omeprazole sulfide as a function of temperature and solvent composition in selected solvents required for the preparation and purification of the products [9]. In our previous research [10] we found that omeprazole sulfide has high solubility in ethanol, and very low solubility in ethyl acetate. To our knowledge, there has been no report about the solubility data of omeprazole sulfide in (ethanol + ethyl acetate) binary solvent mixtures. Thus, systematic and necessary information on the crystallization of omeprazole sulfide was obtained. In this work, the solubility of omeprazole sulfide in (ethanol + ethyl acetate) binary solvent mixtures was measured from 277.65 to 333.15 K at atmospheric pressure (101.3 kPa) by the gravimetric method [11], [12] and experimental solubility data of omeprazole sulfide in binary solvent mixtures in the temperature range from 277.65 to 333.15 K are presented. The combined nearly ideal binary solvent/CNIBS/R–K equation and the Jouyban–Acree equation [13], [14], [15] were applied to correlate with the experimental data. The CNIBS/R–K model has been shown to provide very accurate mathematical representations of solubility in a large number of solvent mixtures and the Jouyban–Acree model predicts the solubility using a minimum number of experimental data points with an acceptable prediction error. The thermodynamic properties of the solution process, including the Gibbs energy, enthalpy, and entropy were calculated by the van’t Hoff analysis. The ethanol + ethyl acetate mixtures were also used for other drugs before like meloxicam [28].

Section snippets

Materials

A white crystalline powder of omeprazole sulfide was supplied by Shanghai Lingfeng Chemical Reagent Co., China and the mass fraction was higher than 0.995, measured by high performance liquid chromatography (HPLC type DIONEX P680 DIONEX Technologies). The melting temperature was 392.15 K determined by differential scanning calorimeter (Netzsch DSC 204). The ethanol, ethyl acetate used for experiment were all analytical purity grade with mass fraction purity higher than 0.995. They were supplied

Solubility data

The solubility data (x1) of omeprazole sulfide in (ethanol + ethyl acetate) binary solvent mixtures with the temperature ranging from 277.65 to 333.15 K are presented in Table 2. For comparison with each of the experimental points, experimental solubility data of omeprazole sulfide in binary solvent mixtures in the temperature range from 277.65 to 333.15 K are presented in Fig. 3 and the lines presented in Fig. 3 correspond to any model results.

From Table 2 and Fig. 3, it can be found that the

Conclusions

In this work new data were provided for the solubility of omeprazole sulfide in (ethanol + ethyl acetate) binary solvent mixtures at temperature range from 277.65 to 333.15 K. We can draw the following conclusions:(1) The solubility of omeprazole sulfide in (ethanol + ethyl acetate) binary solvent mixtures increased with increasing temperature and increased with increasing ethanol content at constant temperature. (2) The solubility data could be successfully correlated using the variants of the

Acknowledgements

This research work was financially supported by the Natural Science Foundation of the Jiangsu Higher Education Institutions of China (Major projects) (grant no. 12KJA180002), the Agricultural Science and Technology Project of JiangSu Province (grant nos. CX(12)3063, CX(12)3060), the Science and Technology Support Program of JiangSu Province (Agriculture) (grant nos. BE2012373, BE2012374), the College Industrialization Project of Jiangsu Province (grant no. JHB2011-16).

We thank the editors and

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