Solubility of Some Drugs in Aqueous Solutions of Choline Chloride-Based Deep Eutectic Solvent Systems: Experimental Data, Modeling, and the Impact of Solution pH

Background: The solubility of drugs in water and organic solvents is a crucial factor in numerous pharmaceutical processes. In recent years, a new type of solvent called deep eutectic solvents (DESs) has been developed as a useful solvent for drugs. Choline chloride-glycerol/urea (ChCl-G/U) systems are DESs recognized as a novel category of environmentally friendly solvents. One recent application of this type of DES in water is the solubilization of drugs. Objectives: This study aimed to investigate the solubility of certain drugs in ChCl-G/U. In addition, the solubilization mechanisms of the DESs studied, and quantitative structure-property relationship (QSPR) models for solubilization were proposed. Methods: The solubility of 13 drugs in an aqueous solution of the ChCl-G/U system was investigated using the shake flask method. The study was conducted at 10% and 50% mass fractions of the studied systems. Multiple linear regression models were used to develop mathematical relationships between the solubilization of the studied compounds in the presence of ChCl-G/U + water mixture using QSPR models. Results: The solubility of the compounds showed a significant increase upon adding ChCl-G/U to the aqueous solutions. Based on the data obtained, QSPR models were developed using solubilization ratio and structural descriptors. Conclusions: The experimental data demonstrates the potential of utilizing ChCl-G/U as a medium to enhance the solubility of poorly soluble drugs in water. Solubilization of solutes in ChCl-G/U + water mixtures could be correlated with the structural properties of drugs. Moreover, the final pH of the solutions in ChCl-U is a critical factor that must be considered when using this system for solubilization.