Recent Advances and Mechanistic Insights into Hydrotropic Solubilization: From Conventional Agents to Novel Combination Strategies
G. W. Ugodi *
Department of Pharmaceutical Chemistry, Enugu State University of Science and Technology, Enugu State, Nigeria.
E. C. Ezeamah
Department of Pharmaceutical Chemistry, Enugu State University of Science and Technology, Enugu State, Nigeria.
*Author to whom correspondence should be addressed.
Abstract
The poor aqueous solubility of emerging drug candidates remains a formidable challenge in pharmaceutical development, directly limiting oral bioavailability and therapeutic efficacy. Hydrotropic solubilization has gained significant attention as a versatile, cost-effective, and environmentally friendly technique to enhance the solubility of hydrophobic drugs without the need for organic solvents. This review provides a comprehensive overview of recent advances in the fundamental mechanisms underlying hydrotropy, including molecular self-aggregation, complexation, and the role of the Minimum Hydrotropic Concentration in initiating the solubilization process. The discussion categorizes hydrotropic agents into synthetic, natural, and novel classes, highlighting a strategic shift toward biocompatible and green alternatives. Findings from literature revealed recent advances in formulation strategies, such as the development of hydrotropic solid dispersions and mixed hydrotropy: a synergistic approach that achieves multifold solubility enhancement while minimizing individual agent concentrations and potential toxicity. By integrating advanced characterization techniques; including spectroscopic, microscopic, and thermodynamic studies with a critical analysis of regulatory and safety considerations for the commercialization of hydrotropic systems. These insights provide a structural framework for overcoming the solubility barrier and optimizing the delivery of next-generation therapeutic agents using hydrotropes.
Keywords: Hydrotropy, hydrotropes, solubility enhancement, drug delivery