Department of Ophthalmology, First Affiliated Hospital, Harbin Medical University, Harbin 150001, China.
Eur J Pharmacol. 2012 Aug 5;688(1-3):1-5. doi: 10.1016/j.ejphar.2011.12.007. Epub 2011 Dec 16.
The bioavailabilities of eye drops are very low, so it is eager to find a safe and effective penetration enhancer to improve drug bioavailability. In our study, the corneas of New Zealand albino rabbit were mounted in the improved Franz diffusion cells for the measurement of fluconazole diffusion across the corneal permeation barrier. The fluconazole concentrations and the cumulative osmolalities were calculated to investigate the changes of permeation parameters of fluconazole through the ex vivo cornea in the presence of different penetration enhancers. Compared with the control group, 0.05% and 0.1% menthol, as well as menthol combined with borneol were considered as the penetration enhancer significantly promoted the permeation of fluconazole through the cornea ex vivo (P<0.05), but the same trend was not found in borneol groups. Furthermore, the combination of borneol and menthol significantly enhanced the permeation rate in the same concentration, compared with their effects when used alone (P<0.01). In order to investigate the feasibility and safety of the mixture, the corneal hydration level or wink frequency over 5 min were detected. So there were no significant differences between the mixture group and the control one. Consequently, menthol combined with borneol can highly enhance fluconazole permeation through the ex vivo cornea. Because of its low irritation, it may be a new efficient and safe penetration enhancer with a good development and application potential.
滴眼剂的生物利用度很低，因此迫切需要寻找一种安全有效的渗透增强剂来提高药物的生物利用度。在我们的研究中，将新西兰白兔的角膜安装在改良的 Franz 扩散池中，以测量氟康唑穿过角膜渗透屏障的扩散情况。计算氟康唑的浓度和累积渗透压，以研究在不同渗透增强剂存在下，氟康唑通过离体角膜的渗透参数的变化。与对照组相比，0.05%和 0.1%薄荷醇以及薄荷醇与冰片的组合被认为是显著促进氟康唑透过离体角膜渗透的渗透增强剂（P<0.05），但在冰片组中没有发现相同的趋势。此外，与单独使用时相比，在相同浓度下，冰片和薄荷醇的组合显著提高了渗透速率（P<0.01）。为了研究混合物的可行性和安全性，在 5 分钟内检测角膜水合水平或眨眼频率。因此，混合物组和对照组之间没有显著差异。因此，薄荷醇和冰片的组合可以显著提高氟康唑通过离体角膜的渗透。由于其低刺激性，它可能是一种新的高效安全的渗透增强剂，具有良好的开发和应用潜力。
