Hydrotropy

Hydrotropy is a phenomenon in solution chemistry where the aqueous solubility of poorly soluble organic compounds is markedly increased upon the addition of small amounts of certain solutes, known as hydrotropes. Unlike micellar solubilization by surfactants, hydrotropy typically involves high polarity or ionic hydrotropes at concentrations below the critical micelle level, and it does not rely on stable micelle formation. The increased solubility is highly system-dependent and can arise from several interacting effects, such as the formation of hydrogen-bonded networks, disruption of the solvent's structure, or the creation of transient, solubilizing aggregates that associate with the solute. The precise mechanism remains a subject of study and may involve a combination of molecular interactions with the solute and the solvent.

Hydrotropy has practical importance in pharmaceuticals, dyes, agrochemicals, and organic synthesis because it enables dissolution and handling of poorly soluble compounds without resorting to organic co-solvents at high levels. Examples of hydrotropes include nicotinamide, urea, and certain sulfonates such as sodium benzenesulfonate or sodium xylene sulfonate, which can substantially increase the solubility of hydrophobic drugs in water. The effectiveness of hydrotropy depends on temperature, hydrotrope concentration, and the solute's chemical nature; high hydrotrope concentrations can alter solution properties, complicate purification, and raise toxicity or environmental concerns. Although not universally applicable, hydrotropy remains a valuable tool in formulation science and process chemistry for solubilizing challenging compounds and enabling liquid handling, extraction, or crystallization workflows.