Ocular irritation potential and cytotoxicity of selected surfactants and cosurfactants: identifying suitable concentrations for topical ophthalmic formulations

The cornea and conjunctiva are particularly susceptible to injury and adverse effects, either induced by topically applied drugs or excipients used in ophthalmic formulations. Surfactants and cosurfactants are important for producing topical eye formulations of poorly water-soluble drugs, yet they have not been always used in concentrations that are nontoxic and non-irritating to the ocular surface. This study systematically compared the cytotoxicity and ocular irritation potential of commonly used ophthalmic surfactants and cosurfactants under standardized experimental conditions using complementary in vitro and ex vivo ocular safety models. The ocular irritation of Tween 80, Cremophor EL, polyethylene glycol 400 (PEG 400) and propylene glycol (PG) was examined using the HET-CAM (conjunctival) and BCOP (corneal) eye assays. The toxic effect of the four excipients after 24 h on HLE-B3 cell growth was investigated and found to be dose-dependent. The highest tolerable concentrations of Tween 80 and Cremophor EL were 0.25% (w/w), whereas PEG 400 and PG were non-toxic at 5% (w/w). Tween 80 and Cremophor EL at 0.25% (w/w) and PEG 400 and PG at 5% (w/w) were all devoid of conjunctival and corneal irritation. This study systematically compared the cytotoxicity and ocular irritation potential of commonly used ophthalmic surfactants and cosurfactants under standardized experimental conditions using complementary in vitro and ex vivo ocular safety models. Interestingly, there is strong agreement between the results obtained using the HET-CAM and BCOP assays, where both have been successfully used to evaluate the potential for ocular irritation caused by the aforementioned excipients.