Mehdizadeh Amir, Ghahremani Mohammad Hossain, Rouini Mohammad Reza, Toliyat Tayebeh
Tehran University of Medical Sciences, Faculty of Pharmacy, Tehran, Iran.
Acta Pharm. 2006 Jun;56(2):219-29.
Drug-in-adhesive patches (DIAPs) of fentanyl were formulated using various pressure sensitive adhesives (PSAs) and various chemical permeation enhancers (CPEs). The effects of PSAs and CPEs on skin permeation of fentanyl from DIAPs were evaluated using modified jacketed Franz diffusion cells fitted with excised rat abdominal skin. It was demonstrated that the permeation rate or steady state flux (J(ss)) of the drug through the excised rat skin was dependent on the viscosity and type of acrylic PSA as well as the type of CPE. Among different acrylic PSAs, Duro-Tak 2054 and Duro-Tak 2516 showed the highest J(ss) of 1.95 microg cm(-2) h(-1) and the lowest J(ss) of 1.43 microg cm(-2) h(-1), respectively. Among the various CPEs used, propylene glycol and polyethylene glycol 400 showed 1.61 and 1.18, the highest and the lowest enhancement ratios (ER) of the skin permeation of fentanyl, respectively. Oleic acid and cetyl alcohol moderately increased the skin permeation of fentanyl. It was also shown that increasing the concentration of CPE led to reduction in the adhesion property of PSA as measured by the 180 degrees peeling strength test. Moreover, it was found that the permeation rate increased as the fentanyl loading increased from 1 to 3%. The skin permeation rate of fentanyl did not increase significantly beyond 3% drug loading. It was concluded that propylene glycol as a CPE and cosolvent in 10% (m/m) with 3% fentanyl loading in Duro-Tak 2054 showed an effective monolithic DIAP for the development of a transdermal therapeutic system for fentanyl.
采用多种压敏胶（PSA）和多种化学渗透促进剂（CPE）制备了芬太尼药物黏附贴剂（DIAP）。使用配备切除大鼠腹部皮肤的改良夹套式Franz扩散池，评估了PSA和CPE对芬太尼从DIAP透皮的影响。结果表明，药物透过切除大鼠皮肤的渗透速率或稳态通量（J(ss)）取决于丙烯酸PSA的粘度和类型以及CPE的类型。在不同的丙烯酸PSA中，Duro-Tak 2054和Duro-Tak 2516的J(ss)分别最高，为1.95μg cm(-2) h(-1)，最低为1.43μg cm(-2) h(-1)。在所使用的各种CPE中，丙二醇和聚乙二醇400对芬太尼皮肤渗透的增强率（ER）分别最高和最低，为1.61和1.18。油酸和十六醇适度增加了芬太尼的皮肤渗透。还表明，通过180度剥离强度试验测量，增加CPE的浓度会导致PSA的粘附性能降低。此外，发现随着芬太尼载药量从1%增加到3%，渗透速率增加。当载药量超过3%时，芬太尼的皮肤渗透速率没有显著增加。得出结论，在Duro-Tak 2054中，丙二醇作为CPE和助溶剂，与3%的芬太尼载药量混合，10%（m/m），显示出一种有效的整体式DIAP，可用于开发芬太尼透皮治疗系统。
