Experimental and thermodynamic modeling of cefixime trihydrate solubility in an aqueous deep eutectic system

Abstract

The solubility of drugs and raw materials in solvents and their mixtures has presented an important role in the pharmaceutical industry. To enhance the solubility of poorly soluble drugs in water, we can use Deep Eutectic Solvents (DESs), which consist of a Hydrogen Bond Acceptor (HBA) and Hydrogen Bond Donor (HBD). In this work, for the formation of the present DES, choline chloride (ChCl) and glycolic acid (GA) with a molar ratio of 1:2 were used. Then, we measured the solubility of cefixime trihydrate in pure water, pure DES and their mixtures at the different weight percent of DES in the temperature range of 298.15 to 323.15 K at atmospheric pressure. The results of experimental solubility data showed that the solubility of cefixime trihydrate was enhanced by increasing the weight percent of DES and temperature. The solubility data of cefixime trihydrate was correlated by local composition models of NRTL (nonrandom two-liquid theory) and UNIQUAC (universal quasichemical), and empirical relations of modified Apelblat and λh Buchowski. Moreover, the thermodynamic properties such as enthalpy, entropy and Gibbs energy of dissolution were calculated for the present systems. The results indicated that the solubility of cefixime trihydrate in both mono solvents, i.e. water and DES, and aqueous DES solution was endothermic. Thus, the main contribution of the dissolution process of cefixime trihydrate in the mono solvents and their mixtures was enthalpy.