目的 制备芹菜素固体分散体胃漂浮片（apigenin solid dispersion gastric floating tablet，Api-SD-GFT），评价其口服药动学行为及体内外相关性。方法 选择羟丙基甲基纤维素（hydroxypropyl methylcellulose，HPMC）K15M、十六醇和NaHCO₃用量为Api-SD-GFT主要影响因素，Api-SD-GFT在2、6、12 h累积释放率的综合评分为响应值，Box-Behnken设计-效应面法优化Api-SD-GFT处方工艺。测定Api-SD-GFT溶蚀率，并研究释药机制。6只Beagle犬随机分成2组，考察Api-SD-GFT药动学行为。采用Loo-Rigelman法考察Api-SD-GFT体内外相关性。结果 Api-SD-GFT最佳处方为HPMC K15M用量为31%，十六醇用量为9%，NaHCO₃用量为9.5%。Api-SD-GFT漂浮时间大于12 h，溶蚀率为（79.49±3.12）%。Api-SD-GFT具有明显的缓释特征，12 h累积释放率达92.1%。释药行为符合一级模型，释药机制为扩散和骨架溶蚀并存。Api-SD-GFT血药浓度（C_max）增加至（464.91±157.04）ng/mL，半衰期（t_1/2）延长至（9.43±2.23）h，相对生物利用度提高至4.50倍。Api-SD-GFT在pH 2.0磷酸盐缓冲液介质中体外释放率与体内吸收率具有相关性。结论 Api-SD-GFT工艺重复性良好，显著提高了芹菜素生物利用度，且体内外相关性良好。

Objective To prepare apigenin solid dispersion gastric floating tablet (Api-SD-GFT), and to evaluate pharmacokinetic behavior and its in vitro-in vivo correlation. Methods Amount of hydroxypropyl methylcellulose (HPMC) K15M, hexadecyl alcohol and NaHCO₃ were selected as main influencing factors, the composite score of cumulative rate at 2, 6, 12 h was used as response value, Box-Behnken design-response surface method was employed to optimize Api-SD-GFT formulation. Corrosion rate of Api-SD-GFT was determined and release mechanism was also studied. Six Beagle dogs were randomly divided into two groups, and the pharmacokinetic behavior of Api-SD-GFT was studied. Loo-Rigelman method was selected to evaluate in vitro -in vivo correlation of Api-SD-GFT. Results Optimal formulation of Api-SD-GFT: Amount of HPMC K15M, Hexadecyl alcohol and NaHCO₃ were 31%, 9% and 9.5%, respectively. The floating time of Api-SD-GFT was more than 12 h, and the corrosion rate was (79.49 ±3.12) %. Sustained-release characteristic of Api-SD-GFT was obvious and cumulative release rate in 12 h was 92.1%. Release behavior was in accordance with the first-order model, and release mechanism was the coexistence of diffusion and matrix erosion. Pharmacokinetic results showed that C_max of Api-SD-GFT was enhanced to (464.91 ±157.04) ng/mL, t_1/2 was prolonged to (9.43 ±2.23) h, and relative bioavailability was enhanced to 4.50 times. In vitro release rate of Api-SD-GFT was correlated with in vivo absorption rate of pH 2.0 phosphate buffer medium. Conclusion Reproducibility of Api-SD-GFT was favorable, bioavailability of apigenin was significantly increased, and the correlation in vitro-in vivo was good.

R283.6

河南省科技公关项目(232102310421);河南省研究生教育改革与质量提升工程项目(YJS2023JD68)