Enhanced Tear Film Concentrations of Cefazolin and Chloramphenicol Using Cross-Linked Hyaluronic Acid in Canine Eyes

Objective: To evaluate the impact of two excipients, 1.4% polyvinyl alcohol (PVA) and 0.75% cross-linked hyaluronic acid (XHA), on tear film concentrations of cefazolin and chloramphenicol. Animals Studied: Ten ophthalmologically healthy dogs. Procedures: Cefazolin and chloramphenicol were compounded into 5.5% and 0.5% solutions, respectively, using either 1.4% PVA or 0.75% XHA. In the first trial, each dog received cefazolin-PVA in one randomly assigned eye and cefazolin-XHA in the contralateral eye. One month later, the experiment was repeated using chloramphenicol formulations. Tear fluid was sampled at 0, 1, 5, 10, 15, 30, 60, 120, 240, 360, and 480 min following eyedrop administration using 2 μL capillary tubes. Tear concentrations of cefazolin and chloramphenicol were measured using UV–Vis spectrophotometry. Results: Tear film concentrations of cefazolin and chloramphenicol were significantly higher with XHA compared to PVA at all time points (p ≤ 0.020), except for baseline (both antibiotics), times 1 min, 60 min, and 120 min for cefazolin. The tear film kinetics exhibited a biphasic pattern, with drug levels decreasing from 0 to 120 min, then slightly increasing between 120 and 360 min before declining again until 480 min. The area under the time-concentration curve (AUC₀₋₄₈₀) was significantly greater with XHA versus PVA formulations (p = 0.002), with a median 2.4 and 4.2 times higher for cefazolin and chloramphenicol, respectively. Conclusion: The cross-linked hyaluronic acid significantly enhanced the retention and overall exposure of both cefazolin and chloramphenicol in the canine tear film. These findings suggest that XHA could serve as a superior delivery vehicle for ocular antibiotics, potentially improving treatment outcomes for ophthalmic infections.