检测方法对利斯的明透皮贴剂体外释放的影响及体外渗透与体内相关性的评价

Effect of Determination Method on in vitro Release Profiles of Rivastigmine Transdermal Patches and Correlation between Penetration in vitro and Absorption in vivo

以市售的2种规格利斯的明透皮贴剂为模型药物,比较采用《中华人民共和国药典》和美国药典收载的释放度测定方法(2种桨碟法和1种转筒法)对体外释放度测定结果的影响。根据利斯的明贴剂对不同种类完整鼠皮(小鼠、大鼠和裸鼠)的体外渗透试验结果,以及文献中的人体药动学数据,初步评价体内外相关性(IVIVC)。单变量方差分析(ANOVA)和模型拟合方法的分析结果表明,不同方法测得的不同规格利斯的明贴剂的释放曲线均存在显著差异;采用鼠类离体皮肤进行利斯的明贴剂的体外渗透试验与人体药动学数据之间呈现出良好的相关性,其中大鼠皮肤的IVIVC关联性最好(R^2=0.9938)。本试验表明,转筒法较适用于利斯的明贴剂的体外释放研究;大鼠皮肤适用于利斯的明贴剂IVIVC的建立。

Three determination methods(two paddle over disk methods and one rotating cylinder method)in Chinese pharmacopeia and US pharmacopeia were adopted to investigate the in vitro release profiles of the commercial rivastigmine transdermal(Exelon®)patches with two specifications(5 cm2 and 10 cm2 patches),and the differences of the results were compared.According to the in vitro transdermal penetration results through murine(mouse,rat and nude mouse)skins and the reported human pharmacokinetic data in the literature,a point-to-point in vivo-in vitro correlation(IVIVC)was established to choose the best skin model for in vitro percutaneous penetration test.The results of univariate analysis of variance(ANOVA)and model-fitting method showed that the release profiles of Exelon®with two specifications determined by different methods had significant differences.There were good correlations between the penetration data through above excised murine skins and the calculated absorption fraction,and the correlation coefficient(R2=0.9938)in the rat model group was the highest among three test groups.It was concluded that the rotating cylinder method in US pharmacopeia was more suitable for evaluating the release of Exelon®Patches with different specifications and rat skin was suitable for the establishment of IVIVC for Exelon®Patches.