Polymer-based amorphous solid dispersion (PASD) technology has attracted attention as one of the most feasible approaches for improving the solubility, dissolution rate, and bioavailability of insoluble drugs. Tegoprazan (TPZ) is a promising new drug used to treat gastroesophageal reflux disease with poor water solubility (~0.03mg/mL). This study developed novel PASD materials containing TPZ. Three polymers were used for this study: PVP, HPMCAS, and carbomer. The PASD powders were prepared via solvent evaporation at 50% drug loading. The physicochemical properties of PASD solids were characterized using PXRD, MDSC, TGA, FT-IR, 1H SS-NMR, and stability testing. PASD powders fabricated with the neutral polymer PVP showed poor stability against drug crystallization. In contrast, those prepared using HPMCAS and carbomer showed no signs of crystallization even after three months of storage at 40oC/75% RH. A correlation between intermolecular interaction and physical stability was inferred for the TPZ PASD formulations. Amorphization of the crystalline TPZ with HPMCAS and carbomer resulted in a greatly increased in vitro dissolution rate. These two polymers showed similar performance, eliciting appreciable improvement in the in vivo absorption tests in rats. In summary, PASD formulations using acidic polymers (HPMCAS and carbomer) are novel formulations for improving the therapeutic effects of TPZ.