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

Abstract

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&#x2009;s, 1, 2, 5, and 10&#x2009;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&#x2009;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&#x2009;&#x2264;&#x2009;.046) and the area-under-the-fluorescein-time curve was twofold greater (p&#x2009;=&#x2009;.005). Compared with control: (i) Tear film concentrations were significantly higher for up to 20&#x2009;min when repeating administration 30&#x2009;s to 5&#x2009;min after the first drop (p&#x2009;&#x2264;&#x2009;.006); (ii) The highest increase in area-under-the-curve was obtained with 2 and 5&#x2009;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&#x2009;<&#x2009;5% from baseline values) was obtained with 5&#x2009;min intervals for 0.3% (55&#x2009;min vs. 15&#x2009;min in control) and 2-5&#x2009;min intervals for 1% solutions (50&#x2009;min vs. 25&#x2009;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&#x2009;min after the first dose.