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Mayssa Attar, Richard Graham, Lisa Borbridge, Sesha Neervannan; The Rate and Extent of Cyclosporine Absorption is Formulation and Tissue Dependent following Topical Ophthalmic Administration. Invest. Ophthalmol. Vis. Sci. 2014;55(13):457.
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Transcellular passive diffusion is thought to be the predominant route of cyclosporine absorption into ocular tissues. This route of absorption is energy independent, occurs across a concentration gradient and the kinetics are heavily dependent on thermodynamics at the formulation−drug−tissue interface. The current study is designed to compare cyclosporine absorption and distribution from an aqueous versus oil based microenvironment following topical ophthalmic administration.
Three prototype formulations were prepared that contained 0.05% cyclosporine (w/v) and varied the amount of oil: prototype 1 (0% oil, aqueous solution), prototype 2 (0.3% oil, light emulsion), prototype 3 (1.25% oil, heavy emulsion). Female New Zealand White rabbits (n=3/timepoint) received a single topical ophthalmic bilateral administration of one of these three prototype formulations. At 0.5, 2, 6, 12, 24, 48 and 144 hours post−dose, ocular tissues and blood samples were collected. Drug concentrations were quantified using LC-MS/MS methods.
Ocular tissue and blood pharmacokinetic parameters are presented in Table 1. Comparison of the pharmacokinetic parameters demonstrates that the rate and extent of absorption is highly dependent on whether cyclosporine partitions into tissue from an aqueous phase versus oil phase microenvironment. Once absorbed into tissue, the kinetics are tissue dependent. Furthermore, the results of prototype 2 versus prototype 3 indicate that relative drug distribution within the different phases of an emulsion affect drug distribution into ocular tissues.
The rate and extent of cyclosporine absorption at the ocular surface is dependent on whether cyclosporine partitions from an aqueous phase or an oil phase into tissue. Once absorbed into tissue, the kinetics are tissue dependent. Furthermore, the relative distribution of cyclosporine in different phases within an emulsion affects the rate and extent of absorption into ocular tissues and blood.
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