Preparation of 5-ASA-loaded Eudragit® S100 nanoparticles by emulsion-based methods: Comparison between solvent evaporation and supercritical fluid extraction

Abstract

Breaking away from the limitations of conventional solvent evaporation (SE), supercritical fluid extraction of emulsions (SFEE) offers a transformative approach to the production of polymeric nanoparticles. In this study, both SFEE and SE were applied to formulate nanoparticles composed of Eudragit® S100 loaded with 5-aminosalicylic acid (5-ASA), a drug widely used in the treatment of inflammatory bowel disease (IBD). A comparison was made between the two methods in terms of particle size distribution, encapsulation efficiency, residual solvent content, and morphology. Formulation efforts focused on obtaining a stable emulsion. A mixed organic phase was required: acetone to dissolve the polymer and a second solvent to solubilise the drug, underscoring the formulation challenge. Among the solvents evaluated, dimethyl sulfoxide (DMSO) was selected due to its ability to maximise 5-ASA solubility, enhance emulsion stability, and its classification as a low-risk Class 3 solvent. SFEE resulted in larger particle sizes (D50 = 165 nm) and slightly lower encapsulation efficiency (EE = 84 %) compared to SE (D50 = 85 nm, EE = 99 %). Despite the high boiling point of DMSO, SFEE achieved a significant reduction in residual solvent content (< 4 %) versus 21 % in SE particles. Both particles showed similar release profiles, with a rapid release of 5-ASA under acidic conditions despite being formulated with a pH-sensitive polymer. This behaviour was likely attributed to the nanometric size and high surface area of the particles, which favoured rapid drug diffusion.