Division of Pharmaceutical Sciences, Arnold and Marie Shwartz College of Pharmacy & Health Sciences, Long Island University, Brooklyn, NY, USA.
Drug Dev Ind Pharm. 2012 Feb;38(2):227-34. doi: 10.3109/03639045.2011.597765. Epub 2011 Aug 24.
The diffusion characteristics of fluoxetine HCl (FLX HCl) and olanzapine (OLZ) alone and in combination with each other were studied to determine their in vitro permeation behavior across a series of gelling agents through a cellulose membrane and human cadaver skin. Klucel 0.5% was selected as the optimal formulation to study their diffusion through human cadaver skin. The release profiles of drugs acting alone and in combinations were identical in the case of the cellulose membrane. However, with human cadaver skin, the permeation of FLX HCl in combination with OLZ drastically increased (732 µg) compared with the release of FLX HCl alone (43.7 µg), while the release of OLZ remained the same whether alone or in combination with FLX HCl (183.7 µg). The results indicate that OLZ enhances the diffusion of FLX HCl through the cadaver skin. Follow-up studies with OLZ were conducted to further investigate this phenomenon and have shown that OLZ enhancement properties are skin reversible as well as concentration dependent. Also, a variety of experiments with different hydrophilic and lipophilic molecules were conducted, and it was found that OLZ enhances the permeation of hydrophilic compounds, while it has no influence on lipophilic compounds. Finally, a number of compounds structurally related to OLZ were investigated as enhancers, and it was determined that piperazine ring attached to the tricyclic system of OLZ is essential for enhancement of FLX HCl (1,837 µg).
研究了盐酸氟西汀（FLX HCl）和奥氮平（OLZ）单独及相互组合时的扩散特性，以确定它们在一系列凝胶剂中的体外渗透行为，这些凝胶剂通过纤维素膜和人体尸体皮肤。选择 Klucel 0.5%作为最佳配方，以研究它们在人体尸体皮肤中的扩散情况。在纤维素膜的情况下，单独作用和组合作用的药物的释放曲线是相同的。然而，对于人体尸体皮肤，与单独释放 FLX HCl（43.7 µg）相比，FLX HCl 与 OLZ 联合释放的渗透量急剧增加（732 µg），而 OLZ 的释放无论是单独还是与 FLX HCl 组合释放都保持不变（183.7 µg）。结果表明，OLZ 增强了 FLX HCl 通过尸体皮肤的扩散。随后进行了 OLZ 的后续研究，以进一步研究这种现象，并表明 OLZ 增强特性是皮肤可逆的，并且与浓度有关。此外，还进行了各种不同亲水性和疏水性分子的实验，发现 OLZ 增强了亲水性化合物的渗透，而对疏水性化合物没有影响。最后，研究了几种与 OLZ 结构相关的化合物作为增强剂，并确定 OLZ 的三环系统上连接的哌嗪环是增强 FLX HCl（1837 µg）的必需条件。
