Mixed Solvency Approach for Solubility Enhancement of Poorly Water-Soluble Drugs: A Comprehensive Review

Abstract

Poor aqueous solubility remains one of the most significant challenges in pharmaceutical formulation development, affecting the dissolution, absorption, and bioavailability of numerous therapeutic agents. The present review comprehensively discusses the mixed solvency approach as an innovative and effective strategy for enhancing the solubility of poorly water-soluble drugs. Mixed solvency is based on the principle that a combination of various water-soluble additives, such as hydrotropes, co-solvents, surfactants, polymers, and buffering agents, can collectively produce a synergistic solubilization effect while minimizing the concentration-related toxicity associated with individual solubilizers. The review highlights the concept of drug solubility, factors affecting solubility, and the challenges posed by poorly water-soluble drugs, particularly those belonging to Biopharmaceutics Classification System (BCS) Classes II and IV. The mechanism, theoretical basis, advantages, limitations, and pharmaceutical applications of mixed solvency are also discussed in detail. Furthermore, a comparative evaluation of mixed solvency with conventional solubility enhancement techniques demonstrates its superiority in terms of simplicity, cost-effectiveness, safety, and versatility. The approach has shown promising results in the formulation of tablets, capsules, oral liquids, injectables, and topical preparations. Overall, mixed solvency represents a practical and economically viable tool for improving drug solubility, dissolution behavior, bioavailability, and therapeutic efficacy in modern pharmaceutical development.