REVIEW ON HYDROTROPIC SOLUBILIZATION TECHNIQUES FOR METHOD DEVELOPMENT AND VALIDATION OF ANTIDIABETIC DRUGS

Abstract Hydrotropic solubilization is an emerging and economical technique widely utilized to enhance the aqueous solubility of poorly water-soluble drugs without the use of organic solvents. The technique involves the addition of large concentrations of hydrotropic agents that increase the solubility of hydrophobic compounds through weak interactions such as hydrogen bonding, π-π interactions, and molecular aggregation. In pharmaceutical analysis, hydrotropy has gained significant importance in the development and validation of analytical methods, particularly for antidiabetic drugs exhibiting poor aqueous solubility. Several oral antidiabetic agents including sulfonylureas, meglitinides, thiazolidinediones, and newer antidiabetic molecules possess limited solubility, thereby creating difficulties in routine quantitative estimation and formulation development. Hydrotropic agents such as sodium benzoate, sodium salicylate, urea, nicotinamide, sodium citrate, and sodium acetate have been successfully employed to improve drug solubility and facilitate spectrophotometric, titrimetric, and chromatographic analysis. Hydrotropic solubilization offers numerous advantages including cost-effectiveness, eco-friendliness, reduced toxicity, elimination of organic solvents, and improved analytical accuracy and precision. The present review highlights the principles, mechanisms, classifications, advantages, limitations, and pharmaceutical applications of hydrotropic solubilization techniques with special emphasis on analytical method development and validation of antidiabetic drugs. The review also discusses various validation parameters including accuracy, precision, linearity, robustness, ruggedness, specificity, and sensitivity according to ICH guidelines. Furthermore, recent advances and future perspectives of hydrotropic solubilization in pharmaceutical analysis are summarized. Keywords: Hydrotropy, Hydrotropic solubilization, Antidiabetic drugs, Method development, Method validation, Solubility enhancement