A major issue of the pharmaceutical industry is the poor solubility, permeability, and bioavailability of most active ingredients. These properties also induce the accumulation of pharmaceuticals in groundwater, surface water, wastewater, soils and biota. Therefore, enhancing the solubility and bioavailability of pharmaceuticals could allow the prescription of lower doses, and could reduce environmental impact. Pharmaceutical solubility can be increased by pH modification, salt formation, ionization, complexation, and co-solvency. Here we report for the first time the use of cyclodextrin-based low-melting mixtures for the solubilization of four steroids: beclomethasone dipropionate, budesonide, fluticasone propionate and mometasone furoate. First, a low-melting mixture was prepared from sulfobutylether-β-cyclodextrin and levulinic acid, and characterized. Then, the shake flask method was used to determine the solubility of the drugs in this low-melting mixture. Results show a 4000-fold increase of the solubility of fluticasone propionate using the low-melting, cyclodextrin-based mixture versus water. This huge solubility enhancement could be explained by the formation of an inclusion complex with the cyclodextrin within the low-melting mixture.