Green solvent-assisted emulsion solvent evaporation approaches for ethyl cellulose micro and nanospheres: Recent advances, formulation strategies, and future perspectives

Polymeric microspheres and nanospheres are versatile carriers for controlled drug delivery, as they can modulate release profiles, enhance stability, and improve therapeutic efficacy. Among fabrication techniques, the emulsion–solvent evaporation (ESE) method is widely used because of its simplicity, reproducibility, and adaptability to various polymers and drugs. Ethyl cellulose, a hydrophobic and chemically stable polymer, is frequently employed as a matrix-forming polymer. Recent trends emphasize the replacement of toxic chlorinated solvents with environmentally safer alternatives such as ethyl acetate and ethanol. High-energy homogenization is applied to achieve nanoscale particles with improved bioavailability. This review critically evaluates formulation strategies, process parameters, and solvent systems for the preparation of microspheres and nanospheres via ESE. Advances in particle size reduction, solvent selection, and surfactant optimization are discussed. A chronological table of previous studies highlights the evolution of this technique. Finally, current challenges, future prospects, and potential green solvent-based approaches for large-scale pharmaceutical applications are summarized.