Measurement and correlation of the solubility of florfenicol in binary 1,2-propanediol + water mixtures from 293.15 K to 316.25 K

Abstract

The solubility of florfenicol in mixed 1,2-propanediol + water solvents was measured by a static analytical method at the temperature ranging from 293.15 K to 316.25 K. The experimental solubility data was correlated by the modified Apelblat equation, the General Single model and the Hybrid model. The results show that: the mole solubility of florfenicol in binary 1,2-propanediol + water mixtures increased with increasing temperature and the mole fraction of 1,2-propanediol in the binary solvent system; the values of the solubility calculated by the three models show good agreement with the experimental value; the OMPD from the modified Apelblat equation, the General Single model and the Hybrid model are 2.48, 2.07 and 5.12, respectively. However, compared to the modified Apelblat equation and the Hybrid model, the General Single model can give more accuracy and reliability of the solubility data. In addition, the discussion of the enthalpy and the entropy for florfenicol in different cosolvents indicated that the dissolution process of florfenicol was endothermic and entropy-driven.

Introduction

The utilization of pharmaceuticals desires the unique solubility data involves liquid solvent selection, such as chemical reaction, pre-formulation, purification and liquid pharmaceutical product [1]. Thus, it is critically important to select the optimum solvents for a particular process. However, choosing solvents for pharmaceutical application has been based on experience. Therefore, a rapid and reliable method for measuring the solubility of drug is necessary for the design of pharmaceutical manufacture effectively.

Florfenicol (2,2-dichloro-N-[(1R,2S)-3-fluoro-1-hydroxy-1-(4-methylsulfonylphenyl)propan-2-yl] acetamide; C₁₂H₁₄CL₂FNO₄S; CAS No: 73231-34-2; Fig. 1) is a fluorinated synthetic analog of thiamphenicol and broad spectrum antibiotic, which belongs to a group of agents used in veterinary medicine named amphenicols [2], [3]. In many countries, it can be used as a replacement for chloramphenicol (CAP) in the treatment of animal diseases and infections. The solubility of florfenicol in methanol, ethanol, acetone and so on has been reported in the literature [4]. However, some hazardous industrial solvents, such as methanol, acetone, etc., possess acute toxicity limiting their application in pharmaceutical preparations. It is well known that the solubility of florfenicol in neat water is too low, and some cosolvents containing water have been evaluated in order to increase the solubility. Moreover, 1,2-propanediol belonging to the nontoxic organic solvents [5] has been used almost exclusively in the production of water-insoluble drug [6]. Furthermore, it can be used as solvent and diluent in pharmaceutical preparations, which is a hydrogen-donor and hydrogen-acceptor compound, and thus, it is miscible with water in all proportions [7]. Thus, it is critically necessary to extend the database on experimental solubility for florfenicol to 1,2-propanediol + water binary mixtures at a certain temperature range.

In the present work, a static method was employed to measure the solubility of florfenicol in several different proportions of binary 1,2-propanediol + water mixtures at the temperature ranging from 293.15 K to 316.25 K. The experimental solubility data was correlated by the modified Apelblat equation, the General Single model and the Hybrid model. The thermodynamic properties of the dissolution process for this system, including the enthalpy and the entropy obtained by van’t Hoff equation, was discussed as well.