Hydrotropy in Pharmaceutical Analysis: Compilation, Evaluation, and Emerging Prospects of Hydrotropic Solvent-Based Analytical Methods

Hydrotropy is a unique, eco-friendly solubilization approach that has gained significant attention in pharmaceutical and analytical sciences. Hydrotropic solvents, composed of one or more hydrotropic agents in aqueous medium, enhance the solubility of poorly water-soluble drugs through non-covalent interactions such as hydrogen bonding, π-π stacking, and hydrophobic association. Although several studies have explored the fundamental aspects and formulation applications of hydrotropy, a consolidated evaluation of its analytical applications has not been conducted. This review comprehensively compiles and critically analyzes the reported analytical methods such as titrimetric, UV-visible spectrophotometric, and HPLC developed using hydrotropic agents over the past two decades. The literature survey revealed that hydrotropic agents, such as sodium benzoate, sodium salicylate, urea, nicotinamide, and sodium citrate, have been widely used to achieve significant solubility enhancement and analytical accuracy. The discussed methods demonstrate improved sensitivity, reproducibility, and environmental compatibility when compared with conventional organic solvent-based techniques. The review also highlights the mechanistic basis of hydrotropy, trends in method development, commonly used hydrotropic systems, and their analytical performance. Furthermore, challenges encountered during method optimization and the scope for applying hydrotropic systems to advanced techniques such as LC-MS and capillary electrophoresis are addressed. The integration of hydrotropy into analytical method development exemplifies the principles of green chemistry, offering a safer, economical, and sustainable alternative for pharmaceutical analysis.