Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, Liaoning, China.
AAPS PharmSciTech. 2019 Apr 25;20(5):174. doi: 10.1208/s12249-019-1370-7.
Chemical penetration enhancers are widely used in transdermal drug delivery system. However, few studies have focused on changes of concentration in chemical penetration enhancers. In this study, the effect of concentrations of enhancers on drug release and its mechanism were investigated. Zolmitriptan (ZOL) was used as a model drug and isopropyl palmitate (IPP) was used as a model enhancer to investigate drug release behaviors in pressure-sensitive adhesives (PSAs). The IPP concentrations were 2, 5, 10, 12, and 15%. Drug release percents increased by 4.8, 11.5, 16, 15.1, and 14.8%, respectively. Interestingly, the linear relationship between concentrations of IPP and release percents was improved in the 0-10% and remained unchanged in the 10-15%. Moreover, thermal and rheology studies were performed to investigate changes of the fluidity of PSAs. FT-IR and molecular dynamics simulation were conducted to confirm the interaction strength among ZOL, IPP, and PSAs. The results elucidated that IPP increased fluidity of PSAs and vied for drug from PSAs. As a result, the interaction among three components played a major role in changing release behaviors of ZOL, but the increased fluidity only worked in the concentration of less than 10%.
化学渗透增强剂广泛应用于经皮给药系统。然而，很少有研究关注化学渗透增强剂浓度的变化。在这项研究中，研究了增强剂浓度对药物释放的影响及其机制。佐米曲普坦（ZOL）被用作模型药物，肉豆蔻异丙酯（IPP）被用作模型增强剂，以研究压敏胶（PSA）中的药物释放行为。IPP 浓度分别为 2%、5%、10%、12%和 15%。药物释放百分比分别增加了 4.8%、11.5%、16%、15.1%和 14.8%。有趣的是，IPP 浓度与释放百分比之间的线性关系在 0-10%范围内得到了改善，而在 10-15%范围内保持不变。此外，还进行了热学和流变学研究，以研究 PSA 流动性的变化。进行了 FT-IR 和分子动力学模拟，以确认 ZOL、IPP 和 PSA 之间的相互作用强度。结果表明，IPP 增加了 PSA 的流动性，并与 PSA 争夺药物。因此，三种成分之间的相互作用在改变 ZOL 的释放行为方面起着主要作用，但增加的流动性仅在浓度小于 10%时起作用。
