Engineering a Stable Tegoprazan Nanosuspension System for Enhanced Dissolution and Oral Bioavailability

Background/Objectives: The aim of this study was to design a nanosuspension (NS) of tegoprazan (TPZ), a novel potassium-competitive acid blocker (P-CAB), to overcome its low aqueous solubility and improve oral absorption. Methods: TPZ NSs were prepared using a lab-scale bead-milling technique. Subsequently, their physicochemical properties, in vitro dissolution profiles, storage stability, and in vivo pharmacokinetic profiles were evaluated. Results: Among various screened stabilizers, polyvinyl alcohol was selected as the suspending agent due to its favorable physicochemical stability. The optimized NS exhibited a mean particle size of approximately 270 nm and a zeta potential of −12.1 mV, preserving the crystalline state of TPZ. In vitro dissolution studies revealed that the NS and its freeze-dried form (NS-FD) markedly enhanced drug dissolution across all tested dissolution media (pH 1.2, 4.0, 6.8, and distilled water) compared to the raw drug material. Furthermore, the NS formulations remained physically and chemically stable for up to 12 weeks under long-term and accelerated storage conditions (25 °C/60% relative humidity (RH) and 40 °C/75% RH). In vivo pharmacokinetic studies in male Sprague–Dawley rats revealed that the oral TPZ NS resulted in approximately a 2.1-fold increase in systemic exposure compared to the raw material and microsuspension. Conclusions: These findings suggest that TPZ NS is a promising strategy to enhance the oral absorption of P-CAB, using a simple, organic-solvent-free fabrication process.