Enteric polymers beyond protection: mechanistic insights and translational implications for supersaturating oral drug delivery systems

Poor aqueous solubility continues to limit oral delivery of many drugs. Weak bases are particularly challenging because they may dissolve in the stomach and subsequently precipitate as the gastrointestinal pH increases. Enteric polymers are therefore being explored not only as protective coatings but also as functional carriers in amorphous solid dispersions (ASDs). This review looks at enteric polymers from the perspective of spatiotemporal regulation of supersaturation, encompassing where drug release begins and what happens to the drug after release. The discussion covers HPMCAS, HPMCP, and methacrylate-based polymers including Eudragit L100-55, Eudragit L100, and Kollicoat MAE 100-55. Published studies on drug release, precipitation, phase behavior, membrane transport, and pharmacokinetics are considered together with regulatory information for selected marketed products. Enteric polymers do not produce uniform effects across formulations. Depending on the drug, polymer grade, drug loading, dissolution conditions, and manufacturing process, they may modulate gastric drug release, influence pH-shift precipitation, and affect nucleation, crystal growth, or drug-rich colloidal phases. However, increased apparent drug concentration does not necessarily indicate a greater concentration of molecularly dissolved drug, membrane transport, or systemic exposure. The review also considers manufacturing-related factors, including spray drying and hot-melt extrusion, and outlines a mechanism-based framework for selecting enteric polymers according to drug-specific biopharmaceutical risks, drug-polymer compatibility, and practical development requirements. Overall, enteric polymers should be selected based on formulation-specific evidence rather than the assumption that pH-dependent release will inherently improve oral bioavailability.