Studies on cationic ocular emulsions containing bipartitioned oil droplets to codeliver cyclosporin A and etodolac.

Background: To prepare ocular emulsions containing bipartitioned oil droplets to entrap cyclosporin A (0.05% w/w) and etodolac (0.2% w/w) by using castor, olive and silicon oils. Methods: The physicochemical characterizations of prepared emulsions were performed. The drug's biodistribution profiles and pharmacokinetic parameters from emulsions were checked using the ultraperformance liquid chromatography–tandem mass spectrometry method in the ocular tissues of the healthy rabbit eye model. Results: The emulsions displayed 365.13 ± 7.21 nm size and 26.45 ± 2.09 mV zeta potential. The ferrying of two drugs after releasing from emulsions occurred across corneal/conjunctival tissues to enter the vitreous and sclera following a single drop administration into the rabbit's eyes. Conclusion: The dual drug-loaded emulsions were more likely to produce synergistic anti-inflammatory activity for managing moderate-to-severe dry eye disease. Summary points Ocular emulsion eyedrops containing bipartitioned oil droplets to entrap cyclosporin A (CsA) and etodolac (Edc) were prepared using castor, olive and silicon oils. The mean particle size, polydispersity index and zeta potential values observed for emulsions were 365.13 ± 7.21 nm, 0.282 ± 0.03 and 26.45 ± 2.09 mV, respectively. The drug-entrapment efficiency values of 77–82% were found for CsA and Edc in emulsions. A faster Edc release from emulsions was observed compared with CsA release in 7.4 pH simulated tear fluid. The combination index value of 0.806 computed from the in vitro protein denaturation assay indicates synergism in the anti-inflammatory activity of emulsions. The cell viability (%) values of 95.710 ± 2.78 to 99.263 ± 0.92% were noticed in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay using human corneal epithelial cells. The ultraperformance liquid chromatography–tandem mass spectrometry bioanalytical method was utilized for the simultaneous estimation of CsA and Edc in ocular tissues of healthy rabbit eyes. The highest area under the curve from 0 to 90 min time period (AUC_{0-90 min}) values were obtained for CsA from emulsions in the cornea followed by conjunctiva, sclera, vitreous and aqueous humor. The highest AUC_{0-90 min} values were found for Edc from emulsion in the cornea, followed by the sclera, conjunctiva, aqueous humor and vitreous. [ABSTRACT FROM AUTHOR]