Ursodeoxycholate (UDCA) has low oral bioavailability and pH-dependent solubility and permeability. Thus, we developed a pH-modified extended-release formulation of UDCA using Na₂CO₃ as the alkalizing agent and hydroxypropyl methylcellulose (HPMC) as the release-modifying agent. The optimized pH-modified controlled-release UDCA formulation, with the UDCA:HPMC:Na₂CO₃ ratio of 200:600:150 (w/w/w), was prepared using a spray-drying method. Then, the formulation’s solubility, dissolution, and pharmacokinetic properties were characterized. In a pH-modified extended-release formulation of UDCA, the solubility of UDCA was increased to 8 mg/mL with a sustained dissolution for 12 h. Additionally, the spray-dried formulation exhibited amorphous states without molecular interaction among UDCA, Na₂CO₃, and HPMC. Moreover, the plasma UDCA concentration of the formulation maintained a higher UDCA concentration for up to 48 h than that of UDCA itself or the non-extended-release UDCA formulation. Consequently, the formulation significantly increased the AUC compared to UDCA or the non-extended-release UDCA formulation in rats. In conclusion, we have improved UDCA’s solubility and dissolution profile by preparing a pH-modified extended-release formulation with the UDCA:HPMC:Na₂CO₃ ratio of 200:600:150 (w/w/w), which effectively increased the oral bioavailability of UDCA by 251% in rats.

中文翻译：

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用喷雾干燥的 pH 调节缓释制剂提高熊去氧胆酸的溶解度和口服生物利用度

熊去氧胆酸盐 (UDCA) 具有低口服生物利用度和 pH 依赖性溶解度和渗透性。_{因此，我们开发了一种使用 Na 2} CO ₃作为碱化剂和羟丙基甲基纤维素 (HPMC) 作为释放调节剂的 pH 调节的 UDCA 缓释制剂。优化的 pH 调节控释 UDCA 配方，UDCA:HPMC:Na ₂ CO ₃比例为 200:600:150 ( w / w / w)，使用喷雾干燥法制备。然后，表征了制剂的溶解度、溶出度和药代动力学特性。在 UDCA 的 pH 调节缓释制剂中，UDCA 的溶解度增加到 8 mg/mL，并持续溶出 12 小时。此外，喷雾干燥制剂呈现无定形状态，UDCA、Na ₂ CO _{3之间没有分子相互作用。}, 和 HPMC。此外，该制剂的血浆 UDCA 浓度比 UDCA 本身或非缓释 UDCA 制剂的血浆 UDCA 浓度保持较高的 UDCA 浓度长达 48 小时。因此，与 UDCA 或非缓释 UDCA 制剂相比，该制剂在大鼠中显着增加了 AUC。总之，我们通过制备 UDCA:HPMC:Na ₂ CO ₃比例为 200:600:150 ( w / w / w ) 的 pH 调节缓释制剂，改善了 UDCA 的溶解度和溶出曲线，有效提高了 UDCA 的溶解度和溶出度。 UDCA 在大鼠中的口服生物利用度提高了 251%。