摘要
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NaHCO_(3)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%,NaHCO_(3)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 NaHCO_(3) 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 NaHCO_(3) 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.
作者
张留超
李高申
刘勇华
朱家豪
ZHANG Liuchao;LI Gaoshen;LIU Yonghua;ZHU Jiahao(Huanghe Science&Technology College,Zhengzhou 450005,China;Shanghai Lei Yun Shang Pharmaceutical Co.,Ltd.,Shanghai 201401,China)
出处
《中草药》
CSCD
北大核心
2024年第19期6519-6528,共10页
Chinese Traditional and Herbal Drugs
基金
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)
作者简介
张留超(1969—),男,学士,副教授,从事中医药及中药新技术研究。Tel:(0371)68786219,E-mail:zlc761213@126.com;通信作者:刘勇华(1979—),男,硕士,副教授,从事临床药学及教学研究。Tel:(0371)68782349,E-mail:lyhbg2020@126.com
