Effect of Formulation Factors on In Vitro Corneal Permeation of Fluconazole Through Excised Sheep Cornea

Abstract

Fungal keratitis is a corneal inflammation with blurred vision and painful eye, which can be treated with fluconazole eye drops. The aim of the study was to find out effect of various formulation parameters on in vitro corneal permeation of fluconazole eye drops. The corneal permeation studies were conducted using freshly excised sheep cornea, mounted between donor and receptor chambers of an all glass modified Frenz diffusion cell, containing 11 ml of ringer bicarbonate (pH 7.4, 34^o±1^oC). At the end of the experiment, each cornea (freed from sclera) was weighed, soaked in 1 ml. methanol, dried overnight at 90 °C and reweighed. From the difference in weights corneal hydration was calculated. Formulation of pH 6 and concentration 2% containing phosphate buffer and mannitol as tonicity modifier, butyl alcohol as preservative, HPMC as viscosity modifier shows maximum permeation. The effects of different formulation parameters on corneal permeation were characterized and the model formulation of fluconazole was developed on the basis of the result. Even though, the marketed formulation (Zocon) comprised of 0.3% w/v of fluconazole and our model formulation contained only 0.2% w/v of fluconazole, the amount of fluconazole permeated from model formulation was much greater than the marketed formulation.