Abstract
Purpose: :
To investigate an aqueous voriconazole (VOR) eye drop in order to increase the corneal permeability and improve ocular bioavailability following topical application.
Methods: :
Hydroxypropyl beta-cyclodextrin (HP-β-CD) was used to formulate an aqueous eye drop to improve aqueous solubility of VOR. A single dose of either VOR suspension (0.5%) (VOR-SP) or VOR (0.5%)/HP-β-CD solution VOR-CD) was applied to rabbits. The aqueous humor and cornea were collected after 5,10,20,30,45,60,90 and 120min. VOR concentrations in aqueous humor and corneas were determined by HPLC after extraction.
Results: :
After topically applying VOR-CD, the VOR concentrations in aqueous humor were 10.83±2.99, 11.37±3.52, 6.22±0.75, 2.89±0.71, 2.07±0.53, 0.86±0.22, 0.30±0.11 and 0.18±0.09µg/ml at 5~120min, significantly higher compared with those of VOR-SP at the corresponding time points (p < 0.05). The half-lives (t1/2) of VOR in aqueous humor for VOR-CD and VOR-SP were 37 and 20 min, respectively. The VOR-CD produced an over 1.7-fold bioavailability (AUC0-120, area under the concentration-time curve between 0 and 120 min) increase in aqueous humor over the VOR-SP. Peak VOR concentration in cornea (43.09±11.83 µg/g) was achieved within 5 min after instillation of VOR-CD, the VOR concentrations in cornea were 43.09±11.83, 41.90±7.86, 36.08±23.38, 14.02±11.29, 25.63±15.92, 29.64±11.96, 26.22±8.11 and 17.13±8.48µg/g at 5~120min, respectively, and were 2.2, 2.6, 4.9, 4.7, 1.7, 3.9, 6.0 and 4.0 times higher than those of VOR-SP at the corresponding time points, respectively. The half-lives (t1/2) of VOR in cornea for VOR-CD and VOR-SP were 241 and 298 min, respectively. The VOR-CD produced an 3.5-fold bioavailability (AUC0-120) increase in corneas over the VOR-SP.
Conclusions: :
VOR-CD is superior to VOR-SP by increasing corneal peneteration and ocular bioavailability.
Keywords: cornea: basic science • antibiotics/antifungals/antiparasitics • keratitis