NANOEMULSION AS A NOVEL OPHTHALMIC DELIVERY SYSTEM FOR ACETAZOLAMIDE

Abstract

Objective: The aim of this work was to formulate the antiglaucoma drug acetazolamide as ocular nanoemulsion of high therapeutic efficacy and prolonged effect. Methods: Eighteen nanoemulsion formulaions consisting of different oils, surfactants and cosurfactants at various ratios and constant water content (39%) were prepared based on their constructed pseudoternary-phase diagrams. According to the In vitro release studies, three nanoemulsions which exhibited fast drug release were used to prepare acetazolamide nanoemulsions with higher water content (59%). The six nanoemulsions at either water content (39 or 59%) were evaluated for their physicochemical properties and ex- vivo corneal permeability. In addition, Draize rabbit eye irritation test was performed. Moreover, biological evaluation of acetazolamide nanoemulsions for their intraocular pressure lowering activity on glaucomatous albino rabbits was carried out. Results: Isopropyl myristate nanoemulsion prepared with cremophor EL and transcutol P exhibited the fastest drug release among all isopropyl myristate nanoemulsions. Oleic acid nanoemulsion prepared with mixture of tween 80 and cremophor EL as surfactants together with transcutol P showed the fastest drug release among other oleic acid nanoemulsion formulae. Similar results were also observed for peanut oil nanoemulsions. The above mentioned formulations either at 39% or 59% water content showed acceptable physicochemical properties and higher acetazolamide permeability coefficient through goat corneas than that reported for the free drug. They also were non irritant to rabbit eye. Therapeutic efficacy testing revealed that peanut oil nanoemulsion at 39% water content showed better and prolonged intraocular pressure lowering effect relative to either commercial brinzolamide eye drops (Azopt®) or the commercial oral acetazolamide tablet (Cidamex®). Conclusion: Acetazolamide was successfully formulated in nanoemulsion form which revealed high therapeutic efficacy in treatment of glaucoma together with a prolonged effect