Increased drug concentration and repeated eye drop administration as strategies to optimize topical drug delivery: A fluorophotometric study in healthy dogs.

OBJECTIVES: Determine tear film kinetics with different fluorescein concentrations and repeated eye drop administration at various time intervals. ANIMALS STUDIED: Six healthy Beagles. PROCEDURES: Six experiments were conducted on separate days: single eye drop administration (control) or two separate eye drops administered at 30 s, 1, 2, 5, and 10 min intervals. For each experiment, one eye received 0.3% fluorescein solution while the other eye received 1% fluorescein solution, and tear fluid was collected with capillary tubes at 0, 1, 5, 10, 20, 30, 40, 50, 60, 90, 120, and 180 min. Fluorescein concentrations were measured using automated fluorophotometry. RESULTS: Compared with 0.3% solution, eyes receiving 1% fluorescein solution had significantly higher tear film concentrations (p ≤ .046) and the area-under-the-fluorescein-time curve was twofold greater (p = .005). Compared with control: (i) Tear film concentrations were significantly higher for up to 20 min when repeating administration 30 s to 5 min after the first drop (p ≤ .006); (ii) The highest increase in area-under-the-curve was obtained with 2 and 5 min intervals for 0.3% (+109%-130%) and 1% solutions (+153%-157%); (iii) The highest increase in median precorneal retention time (defined as tear film concentration < 5% from baseline values) was obtained with 5 min intervals for 0.3% (55 min vs. 15 min in control) and 2-5 min intervals for 1% solutions (50 min vs. 25 min in control). CONCLUSIONS: Drug delivery to the ocular surface can be enhanced by using more concentrated formulations and/or by repeating eye drop administration 2-5 min after the first dose.