Dexamethasone transport and ocular delivery from poly(hydroxyethyl methacrylate) gels

Abstract

We explore ocular delivery of dexamethasone (DX) via poly(hydroxyethyl methacrylate) (PHEMA) contact lenses, which are known to have a much higher bioavailability in comparison to eye drops. Three derivatives of dexamethasone (dexamethasone 21-disodium phosphate (DXP), dexamethasone, and dexamethasone 21-acetate (DXA)) are explored. These drugs are loaded in the gels by soaking in aqueous or ethanol solutions, and also by direct addition of the drug to the polymerizing mixture. Dynamic drug concentrations in the aqueous phase are monitored both in loading and release experiments. The data is utilized to determine the partition coefficients and the mean diffusivity, which includes contributions from both bulk and surface diffusion. Finally we utilize the transport model to predict the bioavailability of the three forms of dexamethasone for drug delivery via contact lenses. The transport of each of the drug is diffusion limited with diffusivities of 1.08 × 10 −11 and 1.16 × 10 −11 m 2/s for DX and DXA, respectively. The diffusivities of DXP depend on concentration and on ionic strength, and are much smaller than those for DX and DXP. The bioavailability for delivery of these drugs via contact lenses is much higher than that for drops, and the bioavailability is the highest for DXA.