不同透皮吸收促进剂对格列美脲体外经皮渗透动力学特征的影响  

Effects of Different Penetration Enhancers on the Kinetics Chara-cter of Permeability of Glimepiride Through Rabbit Skin in vitro

作　　者：张援[1] 许东晖[1] 许实波[1] 陈颖 李向阳 

机构地区：[1]中山大学药学院,广州510275 [2]广东省体育科学研究所,广州510100

出　　处：《中国药科大学学报》2003年第6期509-513,共5页Journal of China Pharmaceutical University

摘　　要：目的 :研究不同透皮促进剂对格列美脲体外经皮渗透的影响 ,筛选有效的复合透皮吸收促进剂 ,提高格列美脲的透皮吸收速率。方法 :采用改良的Franz扩散池 ,以离体新西兰家兔皮肤为透皮屏障 ,用高效液相色谱法测定不同透皮吸收促进剂对格列美脲累积渗透量、透皮吸收速率、透皮时滞和渗透系数等体外透皮吸收动力学参数的影响。对氮酮 (Azone)、丙二醇 (PG)、油酸 (OA)、卡必醇 (Carbitol)、N 甲基 2 吡咯烷酮 (NMP) 5种透皮吸收促进剂单独应用和任意两种合用的促进效果进行考察。结果 :透皮吸收促进剂单独使用时 ,油酸、N 甲基 2 吡咯烷酮和氮酮对格列美脲透皮吸收的促进作用依次增强 ,增透倍数分别为 2 0 1,2 48和 3 3 8;相反 ,卡必醇和丙二醇对格列美脲的透皮吸收起阻滞作用。在 10种复合促进剂中 ,氮酮分别与油酸和丙二醇合用时的透皮渗透量均比单用氮酮高 ,分别使格列美脲渗透系数增大 6 3 1和 4 79倍 ,其中以氮酮和油酸合用促进效果最优。研究了氮酮和油酸最佳促进效果时的配比。实验表明 ,氮酮与油酸的透皮速率常数从大至小依次为 :氮酮与油酸 (1∶1)、氮酮、油酸、氮酮与油酸 (1∶2 ) ,随油酸浓度比例增加 ,药物的累积透过量和增透倍数逐渐降低 ;当氮酮与油酸以相同比例混合使用时 ,具有协同?AIM:To study the effects of different pene tration enhancers on the transcutaneous permeability of glimepiride (Gli) in v itro and therefore to screen out the effective accelerator to enhance the perm eati on rate of Gli. METHOD: Using improved Franz-type diffusion cel l and excised rabbit skin in vitro as transdermal barrier, the kinetics parame ters such as cumulative permeation quantity, permeation rate,permea tion lagged time and permeation coefficient were determ ined by RP-HPL C. Th e enhancement ability of 5 different enhancers such as Azone, PG, OA, NMP and Carb itol, was investigated when used either uniquely or combinatively each other at random. RESULT:when used uniquely, OA, NMP and Azone could e nhance the permeability rate of Gli by 2 01, 2 48 and 3 38 times respectively , w hereas Carbitol and NMP held back the permeation of the drug. Among the 10 mixed enhancers, the cumulative permeation quantity of both Azone-OA an d Azo n e-PG combined system was higher than that of the unique Azone by improving the permeab ility coefficient of Gli as much as 6 31 and 3 38 times respectively. Azone-O A was the best one among them. The optimum ratio of Azone and OA was also observ e d. The effects of Azone and OA on rabbit skin permeation were as follows:Azone -OA(1∶1)>Azone>OA>Azone-OA(1∶2). It showed that further increasing OA conce n tration led to the lower permeability of Gli. When Azone mixed with OA in the sa me p roportion, the system had the largest permeation rate. CONCLUSION:Azone-OA(1∶1) could enhance the permeability of Gli at the largest permeatio n rate, less permeation lagged time and with excellent permeation effect.

关 键 词：格列美脲 透皮吸收 促进剂 高效液相色谱法 

分 类 号：TQ460[化学工程—制药化工]