The effect of vehicle viscosity on the ocular bioavailability of L-653,328

Abstract

The effect of the viscosity of an ophthalmic vehicle on ocular drug penetration has been investigated. Ocular concentrations of L-652,698 have been measured using HPLC and fluorescence detection, in the cornea, aqueous humor and iris + ciliary body of rabbits after instillation of 1% solutions of L-653,328 in 0, 0.2, 0.25, 0.3, 0.35, 0.4 and 0.5% hydroxyethyl cellulose (HEC). Maximum drug concentrations in all three ocular sites increased concomitantly with increase in viscosity. The correlation coefficients between ocular bioavailability, assessed by AUC (0-4 h), and with HEC viscosity were 0.93, 0.96 and 0.83 in cornea, aqueous humor and iris + ciliary body, respectively. When isoviscous solutions containing polyvinyl alcohol were examined, ocular bioavailability was similar in cornea and aqueous humor but reduced by 50% in the iris + ciliary body when compared to the equivalent HEC solution. © 1990.