Characterization of thermal behavior of deep eutectic solvents and their potential as drug solubilization vehicles

Deep eutectic solvent (DES) is a new class of solvents typically formed by mixing choline chloride with hydrogen bond donors such as amines, acids, and alcohols. Most DES's are non-reactive with water, biodegradable, and have acceptable toxicity profiles. Urea-choline chloride and malonic acid-choline chloride eutectic systems were characterized using differential scanning calorimetry (DSC) and thermal microscopy. A potential new 2:1 urea-choline chloride cocrystal with a melting point of 25 degrees C was characterized at the eutectic composition. The formation of this cocrystal suggests that DES should not be universally explained by simple eutectic melting, and may be useful in guiding the search for new DES systems. The lack of nucleation of the malonic acid-choline chloride system prohibited the construction of a phase diagram for this system using DSC. We also investigated possible uses of DES in solubilizing poorly soluble compounds for enhanced bioavailability in early drug development such as toxicology studies. For five poorly soluble model compounds, solubility in DES is 5 to 22,000 folds more than that in water. Thus, DES can be a promising vehicle for increasing exposure of poorly soluble compounds in preclinical studies.