Yuan Jessica S, Acosta Edgar J
University of Toronto, Department of Chemical Engineering and Applied Chemistry, 200 College Street, Toronto, Ontario M5S3E5, Canada.
Int J Pharm. 2009 Feb 23;368(1-2):63-71. doi: 10.1016/j.ijpharm.2008.09.063. Epub 2008 Nov 1.
In a previous article we reported on the use of linker-based lecithin microemulsions as effective transdermal delivery vehicles for lidocaine [Yuan, J.S., Ansari, M., Samaan, M., Acosta, E., 2008. Linker-based lecithin microemulsions for transdermal delivery of lidocaine. Int. J. Pharm. 349, 130-143]. It was determined at that time that the performance of these vehicles was in part due to a permeability enhancement effect, but also due to the amount of lidocaine absorbed in the skin. In the present article we take advantage of this drug absorbed in the skin to produce an extended release profile where the lidocaine-loaded skin is used as an in situ patch. The release of lidocaine from the skin is modeled using a differential mass balance that yields a first order release profile. This profile depends on the mass of drug initially loaded in the skin and a mass transfer coefficient. When the release profile of lidocaine was evaluated as a function of the concentration of lidocaine in the microemulsion, application time, and microemulsion dosage; we observed that all these different conditions only change the mass of lidocaine initially loaded in the skin. However, these parameters do not change the mass transfer coefficient. When the release profile of Types I and II microemulsions was compared, it was determined that the mass transfer coefficient of Type II systems was larger than that of Type I. This suggests that the morphology of the microemulsion plays an important role on the release kinetics. These linker microemulsions were able to release 90% of their content over a 24-h period which rivals the performance of some polymer-based patches. Fluorescence micrographs of transversal cuts of skin loaded with Nile red are consistent with the observed release profiles.
在之前的一篇文章中，我们报道了基于连接剂的卵磷脂微乳剂作为利多卡因有效的透皮给药载体的应用[袁，J.S.，安萨里，M.，萨马安，M.，阿科斯塔，E.，2008年。基于连接剂的卵磷脂微乳剂用于利多卡因的透皮给药。国际药学杂志。349，130 - 143]。当时确定这些载体的性能部分归因于渗透增强作用，也归因于皮肤中吸收的利多卡因量。在本文中，我们利用皮肤中吸收的这种药物来产生缓释曲线，其中负载利多卡因的皮肤用作原位贴剂。利多卡因从皮肤中的释放采用微分质量平衡进行建模，得到一级释放曲线。该曲线取决于最初负载在皮肤中的药物质量和传质系数。当评估利多卡因的释放曲线作为微乳剂中利多卡因浓度、应用时间和微乳剂剂量的函数时；我们观察到所有这些不同条件仅改变最初负载在皮肤中的利多卡因质量。然而，这些参数不会改变传质系数。当比较I型和II型微乳剂的释放曲线时，确定II型系统的传质系数大于I型。这表明微乳剂的形态对释放动力学起着重要作用。这些连接剂微乳剂能够在24小时内释放其90%的含量，这与一些基于聚合物的贴剂的性能相当。负载尼罗红的皮肤横向切片的荧光显微照片与观察到的释放曲线一致。
