Study on solubility of ketoconazole in binary mixtures of water and cosolvents

Abstract

Drug solubility in water and organic solvents plays an important role in many pharmaceutical processes. Co-solvents such as organic solvents and ionic liquids have been widely used as effective and practical methods in the pharmaceutical industry for solubilization. In recent years, a new type of solvents named deep eutectic solvents (DESs) has been developed to be a useful solvent for drugs. Aim Investigation of the solubility of ketoconazole and some drugs (poorly soluble in water) in 2-propanol/PG + water and ChCl: Glycerol/Urea + water. Method The shake flask method was applied in this study. First, the solvent systems were prepared; then an excess amount of drugs was added into glassy vials containing binary solvent mixtures of cosolvent and water. Samples were placed in an incubator at specified temperatures to reach equilibrium. Then they were filtered/centrifuged and diluted with proper solvent mixture and were analyzed by spectrophotometer at specified lambda related to each drug. The concentrations of saturated mixtures were obtained using the calibration curve. The experimental data were fitted to some cosolvency models. Results The solubility data show the solubility of ketoconazole depends on temperatures and solvent composition. The solubility values rise by increasing temperatures and mass fraction of 2-propanol and PG. Furthermore, the results indicate all studied drugs have a significant enhancement in solubility in the presence of ChCl: Urea system as well as the highest solubility values are obtained in 50% mass fraction of ChCl: Urea. As well as, a good and meaningful correlation was obtained between the solubilization ratio and some structural descriptors of drugs. Conclusion 2-propanol and PG are good solubilization agents for enhancing the solubility of ketoconazole. Obtained MRD% values show that the Jouyban-Acree model has a good capability to predict the solubility of ketoconazole in two types of solvent mixtures at temperature ranges. In the other hand, the solubility of investigated drugs in aqueous solution of DES depends on various structural parameters and DES have an appropriate capacity to improve solubility of studied drugs.