磷酸川芎嗪缓释片的研制及兔体内生物利用度测定

Preparation of Sustained-Release Tetramethylpyrazine Phosphate Tablet and its Bioavailability on Rabbits

目的 以羟丙甲纤维素 (HPMC)为骨架材料制备持续释药 12h的磷酸川芎嗪缓释片。方法 分别采用中国药典 1995年版溶出度测定法第 2法及高效液相色谱法测定缓释片的体外释放度及兔体内生物利用度。结果 缓释片体外 1h释药 2 0 %左右 ,12h释药 85 %以上 ,12h内释药平稳 ,释药曲线符合Higuchi方程 ,体外释药受HPMC类型、黏度、用量影响较大。缓释片与市售常释片相比 ,兔体内峰浓度降低 ,达峰时间延迟 ,平均滞留时间延长 ,吸收程度生物等效。结论 缓释片体内外缓释效果良好 ,并具有良好的体内外相关性。

Purpose To prepare the sustained release tablet of tetramethylpyrazine phosphate with hydroxypropylmethylcelluose(HPMC) as matrix material. Methods The paddle method and the HPLC method were erspectively used determined the cumulative drug released in vitro and the serum concentration in vivo . Results The cumulative drug released in the first hour was about 20%,while in 12 hours it was above 85%.Drug release behavior can be best described by Higuchi equation,and the release rate decreased as the viscosity and/or the amount of HPMC increased.Compared with the market tablet on the rabbits,the sustained release tablet had the decreased peak concentration ( P < 0.05 );the prolonged peak time and mean residence time ( P < 0.05 ). Conclusions The matrix tablet was a good sustained release dosage form and it had a good in vitro in vivo correlation.