利用计算模拟技术建立头孢呋辛酯片体内、外相关性溶出度评价方法

Establishing a dissolution evaluation method for cefuroxime axetil tablets for in vitro-in vivo correlation by using computer simulation technology

目的利用计算模拟技术,探索建立前体药物头孢呋辛酯片的体内外相关性预测模型,用于仿制药生物等效性评估。方法参考文献中头孢呋辛酯片口服给药后的PK数据,结合参比制剂的血药浓度数据,利用GastroPlus TM软件搭建头孢呋辛酯片药代动力学模型;结合原研制剂在不同溶出条件、4种溶出介质(pH1.2盐酸溶液、pH4.0醋酸盐缓冲溶液、pH6.8磷酸盐缓冲溶液和水)中的体外溶出行为,筛选适宜的溶出条件;将在不同溶出介质中得到的溶出曲线作为体内释放曲线,预测头孢呋辛酯片在体内PK参数并与参比制剂的临床实测数据进行比较,探讨头孢呋辛酯片体内外相关的溶出度方法。结果成功建立了头孢呋辛酯片体内外相关的溶出度方法:桨法,转速为55 r/min,以pH4.0醋酸盐缓冲液900 mL为溶出介质。结论所建立的头孢呋辛酯片药代动力学预测模型,可用于仿制药的生物等效性虚拟评估,为该药物的质量与疗效一致性评价提供了新思路。

Objective This study explored and established an in vitro-in vivo correlation predictive model for the precursor drug cefuroxime axetil tablets by using computer simulation technology,which was used for the bio-equivalence evaluation of generic drugs.Methods According to the PK parameters from the literature of cefuroxime axetil after oral administration,combining with the data of plasma concentration for reference preparation,GastroPlus TM software was used to establish a pharmaceutical model of cefuroxime axetil tablets.Based on the dissolution behavior in different conditions of dissolution,and in four dissolution media(pH 1.2 hydrochloride acid solution,pH 4.0 acetate buffer solution,pH 6.8 phosphate buffer solution,and water),suitable dissolution conditions were selected.The PK parameters of cefuroxime axetil tablets were predicted using the dissolution curves obtained in various dissolving media as in vivo release curves.These were then compared with the clinical data of the reference preparation,and a dissolution method for cefuroxime axetil tablets for in vitro-in vivo correlation was investigated.Results The dissolution method of cefuroxime axetil tablets for in vitro-in vivo correlation was successfully established by using the paddle method,with a rotational speed of 55 revolutions per minute and a 900 mL dissolution medium of pH 4.0 acetate buffer solution.Conclusion The pharmaceutical prediction model of cefuroxime axetil tablets could be used for virtual evaluation of the bio-equivalence and provided a new idea for evaluating the consistency between the quality and efficacy of the drug.