Effect of nicotinamide and urea on the solubility of riboflavin in various solvents.

Hydrotropy is a solubilization process whereby addition of large amounts of a second solute results in an increase in the aqueous solubility of another solute. Past investigations have focused on the potential interaction of the hydrotropic agent with the solubilized solute. Conversely, this study proposes that at least some hydrotropic agents exert their solubilizing effect predominately by interacting with the solvent. To that end, the effect of two hydrotropic agents, nicotinamide and urea, on riboflavin solubility in aqueous and nonaqueous systems was examined. The term "solutropy" is introduced to describe solubilization by addition of large amounts of a second solute in any solvent. The nonaqueous solvents used included methanol, N-methylformamide, dimethyl sulfoxide, and acetone. In water, methanol, and N-methylformamide, riboflavin solubility was found to increase with increasing nicotinamide concentration; however, riboflavin solubility decreased with increasing nicotinamide concentration in dimethyl sulfoxide and acetone, thus establishing the solvent-dependent nature of solutropy. An examination of solvent properties revealed that the solvent's ability to be both a proton donor and acceptor is important mechanistically, while dielectric constant and polarity are not. The same solvent-dependency was observed with urea, although urea is a poorer solutrope than nicotinamide. This study proposes that some solutropic agents act by changing the nature of the solvent, specifically by altering the solvent's ability to participate in structure formation via intermolecular hydrogen bonding.