Determination and correlation of cefuroxime acid solubility in (acetonitrile + water) mixtures

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Highlights

  • The solubility of cefuroxime acid in different solvents was experimentally determined.

  • The experimental solubility data were correlated by three models.

  • The AIC was used to select the best solubility model.

  • The thermodynamic properties of cefuroxime acid in solution were obtained.

Abstract

The solubility of cefuroxime acid in (acetonitrile + water) mixtures was experimentally determined at temperatures from (278.15 to 313.15) K by using a dynamic method at atmospheric pressure. The solubility increased with the increasing of temperature, and it reached the maximum at acetonitrile molar fraction of 0.713 at constant temperature. The experimental solubility data were correlated well by using the modified Apelblat equation, the λh equation and the van’t Hoff equation, respectively. The Akaike’s Information Criterion (AIC) was used to select the best model for correlating the solubility of cefuroxime acid. Furthermore, the dissolution enthalpy, entropy and Gibbs free energy change of cefuroxime acid were also calculated by using the van’t Hoff equation.

Introduction

Cefuroxime acid (CAS RN: 55268-75-2, figure 1), as an active pharmaceutical ingredient (API), is a common antibiotic drug used for the treatment of bacterial infections. It is also an important intermediate for the production of cefuroxime sodium or cefuroxime axetil in the pharmaceutical industry. Since the quality of cefuroxime acid is largely affected by the crystallization process, it is essential to obtain the optimum crystallization conditions for cefuroxime acid. Many methods can be used to control and optimize the crystallization processes [1], [2], [3]. Among them, choosing a proper solvent system is one of the most important factors since it has a crucial impact on the crystal morphology, form, purity and so on. The solubility data are necessary for the optimization of crystallization processes. Although the solubility data of cefuroxime acid in some pure solvents and mixed solvents have been published [4], to the best of our knowledge, the solubility data of cefuroxime acid in the system of (acetonitrile + water) have not been published.

In this work, the solubility of cefuroxime acid in (acetonitrile + water) mixed solvents was experimentally determined over the temperature range of (278.15 to 313.15) K by using a dynamic method. To extend the applicability of the solubility data, the experimental solubility data of cefuroxime acid were correlated by using the modified Apelblat equation, the λh equation and the van’t Hoff equation. Moreover, the molar enthalpy, entropy and Gibbs free energy change during the dissolution of cefuroxime acid in the above mentioned solvents were also obtained by using the van’t Hoff equation.

Section snippets

Experimental materials

Cefuroxime acid was supplied by North China pharmaceutical Group Corporation (Hebei, China). Acetonitrile (mass fraction purity 0.995) was purchased from Tianjin Kewei Chemical Co., Ltd. (Tianjin, China). All the chemicals were used in experiments without further purification. Distilled-deionised water (conductivities <0.5 us · cm−1) was prepared in our laboratory and used throughout. Detailed information of the materials is listed in table 1.

Apparatus and procedure

The solubility data were determined by using the

The modified Apelblat equation

The modified Apelblat equation which is deduced from the Clausius–Clapeyron equation is wildly used to describe the relationships between the solubility and the temperature. The equation is expressed as follows [7]:lnx=A+B/T+Cln(T),where A, B and C are the empirical constants, T is the absolute temperature. The values of A and B refer to the variations in the solution activity coefficient, and the value of C reflects the effect of temperature on the fusion enthalpy.

The λh equation

The λh equation which is

Properties of pure components

The PXRD pattern of cefuroxime acid is shown in figure 3. The PXRD data verifies the identity and the high crystallinity of the samples used in the research. The thermal analysis (DSC) in figure 4 shows a clear exothermic peak at T = 458.15 K. Since melting process should be endothermic, the exothermic peak at T = 458.15 K is considered to be decomposition peak of cefuroxime acid. It means that the melting process of cefuroxime acid would not happen before the decomposition of the sample. Hence, its

Conclusions

The solubility data of cefuroxime acid in (acetonitrile + water) mixed solvents were experimentally determined by using the dynamic method. It was found that the solubility of cefuroxime acid increased with temperature rising in (acetonitrile + water) system. It is worth noting that the acetonitrile could be used as the co-solvent to dissolve cefuroxime acid. The experimental solubility data of cefuroxime acid in the above mentioned solvents were well correlated by using the modified Apelblat

Acknowledgments

The authors are very thankful to the National Science Foundation of China (No. 21376165) and the National Technology R&D Program from China Ministry of Science and Technology (No. 2011BAD23B02) for the financial support.

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