目的 根皮素（PT）为难溶性药物，且口服相对生物利用度低，通过与缬沙坦（VST）制备成共非晶（CA）提高其溶出速率，从而提高其口服相对生物利用度。方法 以VST为药物载体，PT为模型药物，采用喷雾干燥法制备CA。傅里叶红外图谱（FT-IR）观察样品的官能团结构及分子间相互作用力；差示扫描量热法（DSC）测定玻璃化转变温度（T_g）进一步验证PT和VST分子间的相互作用力；粉末X-射线衍射（PXRD）观察晶体学特性；扫描电子显微镜（SEM）观察样品的微观结构。考察药物在模拟胃液、模拟肠液中的本征溶出，计算溶出速率（IDR）；考察CA在高温、不同湿度下的稳定性；考察CA、PT（200 mg·kg^-1）在大鼠体内药动学。结果 FT-IR和DSC表明CA中PT与VST有较强的分子之间相互作用力，PXRD和SEM证明CA为无定形态，表明PT与VST共喷雾形成了共非晶；CA本征溶出结果表明相较于PT，CA溶出速率有明显提升（P＜0.05）；CA大鼠体内口服相对生物利用度相较原料药提高4.12倍，C_max提高7.44倍。CA在高温条件（50±2）℃表现出良好的稳定性，但湿稳定性较差。结论 PT与VST成功制备成CA，明显的改善了PT的溶出及口服相对生物利用度，并且有较好的热稳定性。

Objective Phloretin (PT) is an insoluble drug with low oral bioavailability.It is proposed to improve its dissolution rate by preparing co-amorphous (CA) with valsartan (VST), so as to improve its oral bioavailability. Methods CA was prepared by spray drying method with VST as drug carrier and PT as model drug. Fourier infrared spectroscopy (FT-IR) was used to observe the structure of functional groups and the intermolecular forces of the samples. The glass transition temperature (T_g) was determined by differential scanning calorimetry (DSC) to further verify the interaction between PT and VST molecules. The crystallographic properties of powder were observed by X-ray diffraction (PXRD). The microstructure of the sample was observed by scanning electron microscopy (SEM). Investigate the intrinsic dissolution of drugs in simulated gastric and intestinal fluids, and calculate the dissolution rate (IDR); Assess the stability of CA under high temperature and different humidity conditions; Investigating the pharmacokinetics of CA and PT (200 mg·kg^-1) in rats. Results FT-IR and DSC show that there is a strong interaction force between PT and VST in CA, and PXRD and SEM show that CA is amorphous, indicating that PT and VST are co-sprayed to form eutectic amorphous. The dissolution rate of CA is significantly higher than that of PT (P < 0.05). The oral bioavailability in vivo was 4.12 times higher than that of the bulk drug, and the C_max was 7.44 times higher. CA showed good stability at high temperature (50±2)℃ , but poor wet stability. Conclusion The CA prepared by PT and VST can obviously improve the dissolution rate and oral bioavailability of PT, and has good thermal stability.

R943

2024年中央引导地方科技发展资金计划项目(2024ZY002);青海省基础研究计划项目(2022-ZJ-748)