A Comprehensive Review of Green Approaches To Drug Solubility Enhancement

This review explores green approaches to enhance poorly water-soluble drug solubility. Implementing sustainable and green techniques, it provides a comprehensive overview of advancements and applications in drug development. Drug solubility is a key challenge in pharmaceutical research, affecting bioavailability and efficacy. Conventional methods often rely on hazardous solvents and energy-intensive processes, posing environmental and safety concerns. This review emphasizes green chemistry principles as sustainable alternatives to enhance solubility while supporting global sustainability goals. Natural and biodegradable polymers in solid dispersions offer effective, eco-friendly solubility enhancement. The application of supercritical CO2 demonstrates significant potential as a green solvent for solubility enhancement, offering scalability while minimizing environmental impact. Plant-derived and renewable excipients offer a sustainable alternative to synthetic additives. Natural polymers face formulation, solubility, and batch variability issues. Deep eutectic solvents and ionic liquids face stability, regulatory hurdles, toxicity risks, and hygroscopicity. Supercritical fluid technology requires costly equipment and precise optimization. Green co-crystallization faces co-former selection, scalability, and stability issues. Further refinement, safety validation, and industrial feasibility studies are needed. Green solubility enhancement methods face scalability, regulatory, and cost challenges. Some offer limited solubility gains and stability issues. Ensuring cost-effectiveness, industrial viability, and compliance is key for broader adoption. Green solubility enhancement offers a sustainable solution to drug solubility challenges. Integrating these methods improves efficiency, safety, and environmental impact. This review highlights the need for further research and the adoption of sustainable drug delivery approaches.