不同动物皮肤和接收液pH值对富马酸福莫特罗体外经皮渗透的影响

Effects of Animal Skin and pH Value of Receiving Solution on in vitro Penetration of Formoterol Fumarate

分别采用大鼠、小鼠、裸鼠的背部皮肤和不同pH 值的接收液体系进行体外透皮试验,考察不同动物皮肤模型和接收液pH值对富马酸福莫特罗体外经皮渗透性能的影响。结果显示,对于富马酸福莫特罗溶液,随接收液pH 值的升高(pH6.0~10.0),大鼠全皮中12h累积透过量逐渐降低,而接收液pH值对裸鼠全皮的经皮行为几乎没有影响。对于富马酸福莫特罗贴片,在大鼠去角质层皮肤中12h累积透过量约是大鼠全皮的7倍;小鼠全皮中12h累积透过量约是裸鼠皮肤的10 倍。本试验提示,不同动物皮肤模型和接收液pH 值会显著影响可解离的富马酸福莫特罗的体外释放和经皮渗透行为,裸鼠或其他少毛囊的皮肤模型更适合用于可解离的弱酸弱碱性药物的体外经皮渗透性能评价。

The aim of this paper is to investigate the influences of different skin models and pH values of receiving solution on the in vitro percutaneous permeability of formoterol fumarate. The drug concentration in receiving solution was determined by HPLC. The transdermal test was carried out with rat, mouse and nude mouse skins as models, respectively. The effect of pH value of receiving solution on dissociated state of formoterol, a weakly basic drug, was also tested. When the donor camber was filled with formoterol fumarate solution, the cumulative amount of drug permeated through the whole skin of rat within 12 h decreased with the increasing of the pH values of receiving solution in the range of pH 6.0 to pH 10.0, while the pH values of receiving solution had no significant influences on percutaneous permeability of drug through nude mouse skin. Then, the formoterol fumarate patches were stuck on the rat skins with or without stratum corneum, mouse skin and nude mouse skin for further research. The results showed that the cumulative amount at 12 h in rat skin removing stratum corneum was about 7 times higher than that in whole skin;while the cumulative amount at 12 h in mouse skin was about 10 times higher than that in nude mouse skin. It indicated that both skin model and pH value of receiving solution had significant effects on in vitro percutaneous permeation of formoterol fumarate. The skin of nude mouse as well as other skin models with less hair follicles was more suitable for the investigation of the percutaneous permeation of both weakly acidic and weakly basic drugs.