School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China.
J Pharm Sci. 2012 Dec;101(12):4540-8. doi: 10.1002/jps.23317. Epub 2012 Sep 12.
The aim of the present study was to develop a transdermal drug delivery system for azasetron and evaluate the correlation between in vitro and in vivo release. The effects of different adhesives, permeation enhancers, and loadings of azasetron used in patches on the penetration of azasetron through rabbit skin were investigated using two-chamber diffusion cells in vitro. For in vivo studies, azasetron pharmacokinetic parameters in Bama miniature pigs were determined according to a noncompartment model method after topical application of transdermal patches and intravenous administration of azasetron injections. The best permeation profile was obtained with the formulation containing DURO-TAK 87-9301 as adhesive, 5% of isopropyl myristate as penetration enhancer, and 5% of azasetron. The optimal patch formulation exhibited sustained release profiles in vivo for 216 h. The in vivo absorption curve in Bama miniature pigs obtained by deconvolution approach using WinNonlin® program was correlated well with the in vitro permeation curve of the azasetron patch. These findings indicated that the developed patch for azasetron is promising for the treatment of delayed chemotherapy-induced nausea and vomiting, and the in vitro skin permeation experiments could be useful to predict the in vivo performance of transdermal azasetron patches.
本研究旨在开发阿扎司琼的透皮给药系统，并评估体外和体内释放之间的相关性。采用双室扩散池体外研究了贴剂中不同的粘合剂、渗透促进剂和阿扎司琼载药量对阿扎司琼透过兔皮渗透的影响。在体内研究中，采用非房室模型法测定巴马小型猪经皮贴剂给药和静脉注射阿扎司琼注射液后的药代动力学参数。含 DURO-TAK 87-9301 作为粘合剂、5%肉豆蔻异丙酯作为渗透促进剂和 5%阿扎司琼的制剂获得了最佳的渗透曲线。最佳贴剂制剂在体内显示出 216 小时的持续释放曲线。使用 WinNonlin®程序进行解卷积处理得到的巴马小型猪体内吸收曲线与阿扎司琼贴剂的体外渗透曲线相关性良好。这些发现表明，开发的阿扎司琼贴剂有望用于治疗延迟性化疗引起的恶心和呕吐，体外皮肤渗透实验可用于预测阿扎司琼透皮贴剂的体内性能。
