Semi‐fluorinated alkanes for topical delivery of Cyclosporine

Abstract

PurposeCyclosporine A (CsA) is an anti‐inflammatory agent that has been frequently used to treat ocular inflammatory conditions, such as dry eye syndrome. However, the poor water solubility of CsA makes it difficult to formulate into an acceptable ocular dosage form. Semi‐fluorinated alkanes (SFAs) are a novel class of inert, non‐toxic and amphiphilic liquids that form clear solutions with CsA and have been suggested as efficient carriers for topical administration of CsA. The aim of this study was to assess the corneal bioavailability of CsA from SFAs compared to currently marketed formulations.MethodsAn ex vivo porcine eye model was used to study the penetration of a) Restasis® (0.05% CsA ophthalmic emulsion), b) Ikervis® (0.1% CsA ophthalmic emulsion), and c) 0.05% or 0.1% CsA in SFAs. The amount of drug penetrated per gram of cornea between 0.5 and 4 h after application was assayed by HPLC and statistically compared using a two‐way ANOVA. Drug distribution in different layers of the cornea was also visualized by substituting CsA with a lipophilic fluorescent dye and viewing corneal sections under a fluorescent microscope.ResultsSignificant improvement in corneal penetration of CsA could be observed for 0.05% CsA in SFAs (C1 h = 5.844 ± 2.408 ng/g) over Restasis (C1 h = 761 ± 221 ng/g), with the area under curve (AUC) being more than 8‐folds greater. The AUC of 0.1% CsA in SFAs (C1 h = 12.556 ± 4.017 ng/g) was 3.6 folds greater than Ikervis (C1 h = 2.900 ± 341 ng/g). Microscopic examinations revealed that the dye incorporated into SFAs tended to accumulate mainly in the corneal epithelium.ConclusionsOverall, this study showed that SFAs can significantly improve the corneal absorption of lipophilic drugs, such as CsA, and could therefore be a promising platform for drug delivery to the eye.