TECHNIQUES FOR SOLUBILITY ENHANCEMENT OF POORLY WATER SOLUBLE DRUGS

Abstract

Poor aqueous solubility is a major challenge in pharmaceutical drug development, as it significantly affects dissolution rate, absorption, and oral bioavailability. A large proportion of newly discovered drug candidates fall under BCS Class II and IV, where solubility becomes the primary limiting factor for therapeutic effectiveness. Therefore, improving solubility is essential to ensure adequate drug concentration in systemic circulation and to achieve optimal pharmacological response. This review discusses the fundamental concepts of drug solubility and highlights various solubility enhancement techniques, including physical modifications such as particle size reduction, crystal engineering, and solid dispersion; chemical approaches like salt formation, prodrug development, and pH adjustment; and advanced methods such as surfactant-based systems, lipid-based drug delivery, nanocrystals, and hot-melt extrusion. The appropriate selection and application of these strategies can significantly enhance dissolution rate, bioavailability, and overall therapeutic performance.