非洛地平-美托洛尔复方贴剂经不同动物皮肤的药物渗透性

目的制备非洛地平-美托洛尔复方透皮贴剂并研究经不同动物皮肤的体外药物渗透特性。方法采用改良的Franz透皮扩散装置,分别以离体小鼠、大鼠和兔皮肤为渗透屏障,生理盐水-乙醇(60:40)为接受液,用HPLC同时测定经皮渗透液中两药物的浓度,并计算渗透动力学参数。结果贴剂中,非洛地平和美托洛尔48 h内均以零级动力学经不同动物皮肤转运,并具一定同步性,动物皮肤对药物渗透性依次为:小鼠>大鼠>兔。结论非洛地平-美托洛尔复方透皮贴剂缓释长效特征明显,药物体外经皮渗透性稳定,各指标均可满足治疗血药浓度的要求。

Comparative study on percutaneous permeability of Felodipine-Metoprolol transdermalpatch through difierent excised animal skins in vitro

OBJECTIVE To prepare Felodipine-Metoprolol transdermal patch and to evaluate its percutaneous permeability through different excised animal skins in vitro.METHODSThe permeate rates of drugs from the patch were determined by modified Franz diffusion cells method.Mouse,rat and rabbit skins were used as permeation barriers.Physiological saline-alcohol(60:40) was used as receptor and the concentrations of felodipine and metoprolol in skin diffuse solution were measured by RP-HPLC simultaneously.RESULTSThe penetration of felodipine and metoprolol in the patch through different excised animal skins in vitro both followed zero-order dynamics in 48h synchronously,and the sequence of their percutaneous permeability through three kinds of animal skin were as follows: mouse>rat>rabbit.CONCLUSIONIt has been demonstrated that the Felodipine-Metoprolol transdermal patch exhibited good controlled release properties and stable percutaneous permeability in vitro which may satisfy the demands of effective blood drug concentration.