The effects of combined menthol and borneol on fluconazole permeation through the cornea ex vivo.
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.
Department of Ophthalmology, First Affiliated Hospital, Harbin Medical University, Harbin 150001, China.
Jingjing
J
Liu
Shaoying
S
Fu
Nan
N
Wei
Yongsheng
Y
Hou
Xiaoning
X
Zhang
Hao
H
Cui
D000818:Animals; D001682:Biological Availability; D001892:Camphanes / Q000009:adverse effects / Q000494:pharmacology*; D003315:Cornea / Q000187:drug effects* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D015725:Fluconazole / Q000493:pharmacokinetics*; D008610:Menthol / Q000009:adverse effects / Q000494:pharmacology*; D010539:Permeability / Q000187:drug effects; D011817:Rabbits; D012449:Safety
D001892:Camphanes; D008610:Menthol; D015725:Fluconazole; C022871:isoborneol