Cyclosporin A Ophthalmic Study Of The Microemulsion

Most dry-eye symptoms result from an abnormal, nonlubricativeocular surface that increases shear forces under the eyelids anddiminishes the ability of the ocular surface to respond to environmentalchallenges. This ocular-surface dysfunction may result fromimmunocompromise due to systemic autoimmune disease or may occurlocally from a decrease in systemic androgen support to the lacrimalgland.Eye drops are the most used dosage form by the ocular route, in spiteof their low bioavailability. Cyclosporine A (CsA) is aproved to be usedin the treatment of dry eye syndrome. The currently available systemsusing oils to deliver CsA topically are poorly tolerated and provide a lowbioavailability. Microemulsions are promising systems for topical oculardrug delivery. They can increase water solubility of the drug and enhancedrug absorption in the eye. The present study describes the developmentand characterization of an oil-in-water microemulsion containingCyclosporine A and the evaluation of its pharmacodynamics in rabbitsafter topical ocular application.The microemulsion was prepared by the titration technique. Itsphysico-chemical characteristics and stability were determined. Theocular irritation test of this system was studied in white rabbits, and developed a simple dry eye model in the rabbit, induced by daily repeatedinstillations of 1.0% atropine sulphate. The evolution of the dry eyesyndrome in the animals was assessed by the Schirmer I test and byexamination of the cornea after fluorescein staining.The developed system showed an acceptable physico-chemicalbehaviour and presented good stability for 3 months. The ocular irritationtest used suggested that the microemulsion did not provide significantalteration to eyelids, conjunctiva, cornea and iris. The dry eye modelproduced rapidly some typical dry eye symptoms and could besatisfactorily used for a preliminary assessment of the protective activityof Cyclosporine A microemulsion. The pharmacodynamics resultsshowed that Cyclosporine A microemulsion was better than that of theconventional preparation (P＜0.05).The microemulsion-based Cyclosporine A eye drop is advantageousfor ophthalmic use because it is well-tolerated in the eye and seemed toprovide a higher degree of bioavailability. Topical CsA microemulsionsignificantly improve the dry eye syndrome.