Preparation and evaluation of tegoprazan tablets using long-term crystallization-suppressing solid dispersion technology

초록

Purpose This study aimed to develop a polyvinylpyrrolidone (PVP)-based amorphous solid dispersion (ASD) formulation to prevent the crystallization of tegoprazan (TPZ) during long-term storage and to establish a foundation for commercial tablet manufacturing. Methods The solubility of TPZ-ASD was evaluated in water and buffer solutions. Flowability was assessed using Carr’s Index and the Hausner ratio (HR), and the results were compared with those of amorphous TPZ (TPZ-Am) and crystalline TPZ (TPZ-Cr). Recrystallization during storage was monitored using differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) under both long-term (25 ℃, 60% relative humidity [RH]) and accelerated (40 ℃, 75% RH) conditions. The dissolution profiles of tablets prepared with TPZ-ASD were compared with those of a commercial product. Results TPZ-ASD exhibited approximately a 20-fold increase in water solubility compared to TPZ-Cr and showed enhanced solubility across all tested pH conditions. Carr’s Index and HR value indicated that TPZ-ASD had better flowability than both TPZ-Cr and TPZ-Am. Stability analyses using DSC and PXRD revealed no recrystallization for up to 24 months (raw material) and 12 months (tablet) under long-term storage conditions and for 6 months under accelerated conditions, respectively. A human pharmacokinetic study demonstrated that the TPZ-ASD tablet was bioequivalent to the commercial product. Conclusion The PVP-based solid dispersion effectively inhibited TPZ crystallization over an extended period. Furthermore, the TPZ-ASD formulation proved successfully applicable to the manufacturing process, and the commercial potential of this technology was identified in a Phase 1 clinical pharmacokinetics study.

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