Modern Approaches for Enhancing Drug Solubility: An Overview of Technologies

Solubility refers to the ability of a solute to dissolve in a solvent under specific conditions of pressure and temperature to form a uniform solution. However, many active pharmaceutical ingredients (APIs) are poorly water-soluble or hydrophobic, making solubility one of the most challenging factors in drug formulation development. Low aqueous solubility often leads to reduced bioavailability, limiting the drug’s therapeutic potential and overall product performance. Therefore, enhancing solubility is essential to ensure optimal drug absorption and efficacy. Many promising drug candidates fail to progress in development due to poor solubility, despite having high pharmacological activity. To address this issue, various solubility enhancement strategies are employed. These include chemical modifications such as salt formation and co-crystallization; physical approaches like polymorph and habit modification; complexation techniques including physical mixtures and inclusion complexes; surfactant-based methods like self-emulsifying drug delivery systems (SEDDS); solid dispersion techniques; pH adjustment; and advanced technologies like liquisolid systems, supercritical fluid processing, and polymer-based modifications. This article aims to consolidate and apply multiple solubility enhancement techniques to improve the aqueous solubility and therapeutic performance of poorly water-soluble drugs.