[关键词]
[摘要]
目的 制备欧前胡素固体分散体（imperatorin solid dispersion，IMP-SD）凝胶骨架缓释片（hydrogel matrix sustained-release tablets）（IMP-SD-HMSRT），并研究口服药动学行为及体内外相关性。方法 溶剂挥发法制备IMP-SD。在单因素考察的基础上，选择HPMC K15M用量、聚乙二醇（PEG）400比例和PEG总用量为主要影响因素，缓释片在2、6、12 h累积释放率的综合评分为响应值，采用Box-Behnken设计-效应面法优化IMP-SD-HMSRT最佳处方，并考察在家兔体内的药动学行为。利用Loo-Rigelman法评价其体内外相关性。结果 IMP-SD-HMSRT最佳处方为HPMC K15M用量为48 mg/片、PEG 400比例为58%、PEG总量为26.5 mg/片。HMSRT的12 h累积释放率达到95.54%。药动学结果显示IMP-SD- HMSRT的Cmax波动小，tmax延后至（4.08±0.43）h，与欧前胡素普通片相比IMP-SD-HMSRT的相对生物利用度提高至219.76%。IMP-SD-HMSRT在pH 6.8磷酸盐缓冲液中体外释药行为与体内吸收存在相关性。结论 IMP-SD-HMSRT释药缓慢，促进了药物吸收，体内吸收与体外释药具有良好的相关性。
[Key word]
[Abstract]
Objective To prepare imperatorin solid dispersion (IMP-SD) hydrogel matrix sustained-release tablets (IMP-SD- HMSRT), and investigate the pharmacokinetic behavior and in vivo-in vitro correlation. Methods Solvent evaporation was used to prepare IMP-SD. On the basis of single factor investigation, HPMC K15M dose, PEG 400 proportion and amounts of PEG dose were selected as main influencing factors, composite score of cumulative rate of 2, 6, and 12 h of IMP-SD-HMSRT was used as response value, Box-Behnken design-response surface method was employed to optimize formulation of IMP-SD-HMSRT, and the pharmacokinetic behavior in rabbits was studied. Loo-Rigelman method was used for the evaluation of in vivo and in vitro correlation. Results The optimal formulation of IMP-SD-HMSRT:HPMC K15M dose was 48 mg/tablet, PEG 400 proportion was 58%, PEG total dose was 26.5 mg/tablet. The accumulative release of IMP-SD-HMSRT could achieve 95.54% whthin 12 h. Pharmacokinetic results showed that Cmaxfluctuated slightly, and tmax was delayed to (4.08 ±0.43) h. The relative bioavailability of the IMP-SD-HMSRT was enhanced to 219.76% comparing to imperatorin tablets. In vitro release behavior of IMP-SD-HMSRT in pH 6.8 phosphate buffer saline was associated with its in vivo pharmacokinetics. Conclusion The drug release of IMP-SD-HMSRT was slowly, and promoted absorption. The correlation between the absorption in vivo and release in vitro is fine.
[中图分类号]
R283.6
[基金项目]
国家自然科学青年基金资助项目（51804021）
