Mucoadhesive Polymers Enhance Ocular Drug Delivery: Proof of Concept Study with 0.5% Tropicamide in Dogs

Purpose: To assess the efficacy of 0.5% tropicamide applied after topical administration of 1.4% hydroxyethyl cellulose (HEC) or 1.2% hyaluronic acid (HA) at different time intervals.Methods: Eleven healthy Labrador retriever dogs were used. The study consisted of 7 trials in which pupil diameter (PD) was measured every 30 min for 7 h after drug administration. In trial 1, PD was measured after tropicamide application (control). In trials 2-7, PD was measured after treatment with tropicamide 10 s, 1 and 5 min after application of HEC or HA. Data were analyzed using analysis of variance and post hoc Holm-Sidak tests.Results: Maximal PD (mean +/- standard deviation) was significantly greater (P < 0.001) in 5 of 6 experimental trials, with the greatest PD recorded when HEC was applied 1 min (12.2 +/- 0.4 mm) and HA 10 s (12.3 +/- 0.5 mm) before tropicamide, compared with 11.2 +/- 0. 7 mm in control trial 1. PD >10 mm was maintained for 2.75-5 h in trials 2-7 and 2.25 h in trial 1 (P < 0.001). Area under the PD-time curve ranged from 61.9 to 71.3 +/- 2.9 mm center dot hours in trials 2-7, significantly greater than 59.3 +/- 1.8 mm center dot hours in control trial 1 (P <= 0.031).Conclusions: Tropicamide efficacy was enhanced by prior administration of a mucoadhesive polymer. Additional studies are needed to determine if HEC and HA of varying concentrations similarly extend and potentiate the effect of other topical ophthalmic drugs in canine eyes.