Partially Neutralized Methacrylic Acid-Ethyl Acrylate Copolymers: Mechanistic Insights, Formulation Advances, and Translational Frontiers in Oral Drug Delivery

Abstract

Oral drug delivery remains constrained by poor solubility, acid-labile degradation, and erratic gastrointestinal absorption. Conventional enteric polymers address these barriers partially but suffer from limited mechanical flexibility and aqueous insolubility. Partially neutralized methacrylic acid-ethyl acrylate (MAA-EA) copolymers overcome these limitations by modifying charge density and ionization behaviour, enabling precise pH-triggered dissolution above pH 5.5. Ternary amorphous solid dispersions (ASDs) combining Eudragit® L100-55 with hydroxypropyl cellulose maintained supersaturation for approximately 70 minutes, compared to 30 minutes with L100-55 alone. These copolymers support diverse formulation platforms, including self-emulsifying pellets, ASDs, pH-responsive nanoparticles, electrospun fibres, and 3D-printed dosage forms. Their application extends to fixed-dose combinations, site-directed protein carriers, and paediatric-friendly systems, reflecting broad translational potential. Remaining challenges, including moisture sensitivity, physiological pH variability, and regulatory gaps for nanostructured platforms, define the frontiers that this review critically examines.