Enhancing the Dissolution of Hydrophobic Actives: A Comparative Review of Traditional and Advanced Formulation Technologies
Year: 2026
Type: article
Abstract: Over 40% of newly discovered drug candidates fail to progress through the development pipeline due to inadequate biopharmaceutical properties, primarily poor aqueous solubility and slow dissolution.For molecules belonging to BCS Classes II and IV, these solubility restrictions dictate poor oral absorption and highly variable bioavailability.To address this challenge, this review delivers a comprehensive and comparative analysis of conventional, advanced, and emerging solubilisation technologies.Traditional formulation approaches including pH adjustment, co-solvency, salt formation, hydrotropy, cyclodextrin inclusion complexes, and polymeric solid dispersions are reviewed alongside their key benefits and limitations, such as physical instability and precipitation risks.This work subsequently transitions into modern physical modifications, evaluating advanced nanoscale systems (such as nanosuspensions, solid lipid nanoparticles, polymeric micelles, and electrospun nanofibres) and supercritical fluid processing.Special attention is paid to emerging chemical and molecular strategies, namely mesoporous silica adsorption, deep eutectic solvents (DESs), and ionic liquids (ILs), which offer highly tunable polarities and strong molecular interactions.Through a detailed case study of the hydrophobic active curcumin, we compare the quantitative dissolution efficiencies, scalability, and pharmacokinetics of these diverse techniques.Ultimately, we conclude that achieving reproducible bioavailability depends on selecting a tailored solubilisation platform that balances the unique crystal properties of the drug with industrial scalability and formulation stability. Suggested Keywords• Solubility enhancement • BCS Class II and IV drugs • Solid dispersions & Hot-melt extrusion • Nanotechnology & Nanosuspensions • Deep eutectic solvents & Ionic liquids • Dissolution efficiency (Curcumin)
Language: English
Subfield: Pharmaceutical Science
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W7204264877