Iontophoresis as a method of enhancing drug delivery to the anterior segment of the eye
Description
Iontophoresis, the application of low-level electrical current to promote movement of a substance across a boundary, was investigated in conjunction with topically applied eye medicines with easy to determine effect times through noninvasive methods (dilation/reversal, and intraocular pressure [IOP] lowering [glaucoma] medications) to assess their effect on tissues of the anterior segment of the eye Initial study focused on chemical stability of ophthalmic medications subjected to applied electrical currents. Twenty-four tested drugs (dilators, constrictors, IOP-reducing drugs, and anesthetics) underwent eleven iontophoretic treatment levels (10muA-20mA) for durations of two minutes. Macroscopic observations, pH level, HPLC profiles, and solution resistivity were noted. All tested drugs remained chemically stable in the current density range of interest (≤1.25mA/cm2); a subset of fourteen drugs displayed minimal changes through all currents Four of these drugs were used for subsequent in vivo testing in adult rabbits: phenylephrine hydrochloride, pilocarpine hydrochloride, timolol hemihydrate, and brimonidine tartrate. Three iontophoretic treatment conditions were investigated for dilation/reversal (0.5mA for 60sec, 1mA for 30sec, and 1mA for 60sec), and one treatment condition for IOP lowering drugs (1mA for 60sec), lontophoretic current was delivered via a TENS electrode atop a closed eyelid after one drop of drug was administered topically to the eye. No significant difference was observed between iontophoretically treated and untreated eyes in time-to-effect for dilation using phenylephrine hydrochloride (p=0.22, n=8) or reversal using pilocarpine hydrochloride (p=0.32, n=8), or for maximum obtained pupil size (p=0.51, n=8). A significant reduction in time-to-effect was observed iontophoretically for the IOP lowering medication timolol hemihydrate (p=0.05, n=2), but not for brimonidine tartrate (p=0.15, n=3) The in vitro iontophoretic method employed in this study successfully verified chemical stability after current application for 14 of the 24 tested drugs, of which 4 drugs were subsequently tested for iontophoretic use in vivo. The particular in vivo iontophoretic method employed in this study, while designed around constraints of patient acceptance associated with eventual deployment to human clinical use, was unsuccessful at achieving efficiency that would justify further development. Future refinements to the in vivo method may alter this assessment