Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, China.
Biopharm Drug Dispos. 2010 Mar;31(2-3):138-49. doi: 10.1002/bdd.698.
The purpose of this study was to formulate a drug-in-adhesive (DIA) transdermal patch containing letrozole, a third generation aromatase inhibitor for the treatment of breast cancer, using pressure-sensitive-adhesives (PSAs) and to evaluate the percutaneous penetration and pharmacokinetics of letrozole after transdermal administration, compared with that for the oral route. The formulation factors for such a patch, including the PSAs, enhancers and amount of drug loaded were investigated. Among the tested preparations, the formulation with DURO-TAK 87-4098, Azone and propylene glycol showed the highest letrozole permeation. The pharmacokinetic characteristics of an optimized DIA patch containing letrozole were determined using rats, while orally administered letrozole in solution was used as a control. The pharmacokinetic parameter, such as the mean residence time (MRT) was significantly (p<0.05) different following transdermal administration compared with oral administration. The in vivo results observed with the patches in rats were in good agreement with the plasma concentrations predicted from the in vitro penetration data. As a patient-friendly, convenient, high local drug concentration and sustained dosing therapeutic system, the transdermal patches incorporating letrozole provide a useful strategy for the prevention and treatment of breast cancer.
本研究旨在采用压敏胶（PSA）制备包含第三代芳香酶抑制剂来曲唑的透皮贴剂，用于治疗乳腺癌，并与口服途径相比，评价来曲唑经皮给药后的透皮渗透和药代动力学。考察了透皮贴剂的制剂因素，包括 PSA、促进剂和载药量。在测试的制剂中，含 DURO-TAK 87-4098、氮酮和丙二醇的制剂显示出最高的来曲唑渗透。采用大鼠确定了含有来曲唑的优化 DIA 贴剂的药代动力学特征，以溶液形式口服给予来曲唑作为对照。与口服给药相比，经皮给药后的平均驻留时间（MRT）等药代动力学参数有显著差异（p<0.05）。在大鼠中观察到的贴剂的体内结果与从体外渗透数据预测的血浆浓度一致。作为一种患者友好、方便、局部药物浓度高和持续给药的治疗系统，包含来曲唑的透皮贴剂为预防和治疗乳腺癌提供了一种有用的策略。
