EDTA decreases in vitro transcorneal permeation of fl uconazole in phosphate buffer through excised sheep cornea

Abstract

Introduction: According to the World Health Organization, corneal diseases are a major
cause of vision loss and blindness, second only to cataract in overall importance. Fungal
keratitis is a major blinding eye disease in Asia. In epithelia, calcium has been implicated
in the maintenance of intercellular matrix and therefore may be a key factor determining
the size of potential paracellular routes for drug transport. Although the effects of
chelating agents such as EDTA on the permeability of inorganic and organic solutes
have been well documented in other epithelia, as well as the corneal endothelium, no
definitive studies examining the effects of these compounds upon corneal epithelia have
been reported. Materials and Methods: The corneal permeation studies were conducted
using freshly excised sheep cornea, mounted between donor and receptor chambers of an
all glass-modified Franz diffusion cell, containing 11 ml of ringer bicarbonate (pH 7.4,
34o
±1o
C). At the end of the experiment, each cornea (freed from sclera) was weighed,
soaked in 1 ml of methanol, dried overnight at 90°C and reweighed. From the difference
in weights corneal hydration was calculated Results: Fluconazole ophthalmic solutions
(0.2% w/v, pH 6.0) containing EDTA shows significant difference in Papp 1.51×106
(cm/s) as compared to fluconazole ophthalmic solutions (0.2% w/v, pH 6.0) without
EDTA showing 2.37×106 (cm/s). Conclusions: Use of ethylene diamine tetraacetate as
chelating agent in fluconazole ophthalmic solutions significantly decreased the corneal
permeability of fluconazole.