Kanikkannan N, Andega S, Burton S, Babu R J, Singh Mandip
Division of Pharmaceutics, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, Florida 32307, USA.
Drug Dev Ind Pharm. 2004 Feb;30(2):205-12. doi: 10.1081/ddc-120028716.
The present study was undertaken to prepare and evaluate monolithic drug-inadhesive type transdermal patches of melatonin containing penetration enhancers such as fatty alcohols, fatty acids, and terpenes. The patches were prepared using Eudragit E 100 as the adhesive polymer. The release profile of melatonin from control as well as enhancer-containing patches showed an initial burst of melatonin release for up to 4 hours and then a plateau after 8 hours. The release profiles of melatonin from patches containing various enhancers were similar to the control patch. However, the addition of enhancers in the patch increased the permeation of melatonin through hairless rat skin. The flux values of patches containing octanol, nonanoic acid, and myristic acid were higher than the control patch (no enhancer), but the differences were not statistically significant (P>0.05). Decanol, myristyl alcohol, and undecanoic acid at 5% concentrations showed significantly higher flux values through hairless rat skin (enhancement ratios 1.7, 1.5, and 1.6 for decanol, myristyl alcohol, and undecanoic acid, respectively) (P<0.05). Menthol and limonene at 5% w/w showed maximum permeation of melatonin among all enhancers studied (enhancement ratios=2.1 and 2.0 for menthol and limonene, respectively) (P<0.001). In general, there was about 4-6 hours of lag time observed before a steady state flux of melatonin was achieved. Though the flux of melatonin observed in the present study is 5-10 times higher than the required delivery rate in humans, it must be noted that the present study was performed using hairless rat skin, which is generally more permeable compared to human skin. Further studies using human skin would prove the usefulness of these patches.
本研究旨在制备并评估含有渗透促进剂（如脂肪醇、脂肪酸和萜类化合物）的褪黑素整体式药物黏附型透皮贴剂。使用Eudragit E 100作为黏附聚合物制备贴剂。褪黑素从对照贴剂以及含促进剂贴剂的释放曲线显示，褪黑素在最初4小时内有一个释放高峰，然后在8小时后达到平稳状态。含不同促进剂的贴剂中褪黑素的释放曲线与对照贴剂相似。然而，在贴剂中添加促进剂增加了褪黑素透过无毛大鼠皮肤的渗透率。含辛醇、壬酸和肉豆蔻酸的贴剂的通量值高于对照贴剂（无促进剂），但差异无统计学意义（P>0.05）。5%浓度的癸醇、肉豆蔻醇和十一烷酸透过无毛大鼠皮肤显示出显著更高的通量值（癸醇、肉豆蔻醇和十一烷酸的增强比分别为1.7、1.5和1.6）（P<0.05）。在所有研究的促进剂中，5% w/w的薄荷醇和柠檬烯显示出褪黑素的最大渗透率（薄荷醇和柠檬烯的增强比分别为2.1和2.0）（P<0.001）。一般来说，在达到褪黑素的稳态通量之前观察到约4 - 6小时的滞后时间。尽管本研究中观察到的褪黑素通量比人类所需的给药速率高5 - 10倍，但必须注意的是，本研究是使用无毛大鼠皮肤进行的，与人类皮肤相比，无毛大鼠皮肤通常更具渗透性。使用人类皮肤的进一步研究将证明这些贴剂的实用性。
