Abstract
The effects of N-trimethylchitosan (TMC) on the transcorneal transport of dexamethasone, taken as a marker of the transcellular penetration route, and of tobramycin, a marker of the paracellular route, were studied by assessing the TMC effect on the intraocular pharmacokinetics of each marker. The drugs were topically applied via erodible inserts (weight, 20 mg; diameter, 6 mm; drug dose, 0.3 mg) based on poly(ethylene oxide), containing 10% w/w medicated TMC microspheres (diameter < 2.5 microm). Before application, drug release and insert erosion kinetics, and release mechanism were studied in vitro. With either drug, introduction of 10% TMC into insert did not substantially alter the release and erosion rates, hence this formulation was apt to isolate the transcorneal penetration enhancing effect of TMC. Ocular pharmacokinetics were determined in the rabbit model. TMC produced significant increases of dexamethasone Cmax (5.69 +/- 0.49 vs. 3.07 +/- 0.31 microg/ml) and AUC (619.3 +/- 32.5 vs. 380.5 +/- 32.0 microg min/ml) in the aqueous with respect to the reference TMC-free insert. On the other hand, TMC was unable to yield tobramycin concentrations in the aqueous exceeding the determination limit (0.5 microg/ml). In conclusio...Continue Reading
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