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

Sep 28, 2026

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Objective evaluates how two excipients—1.4% polyvinyl alcohol (PVA) and 0.75% cross-linked hyaluronic acid (XHA)—change tear film concentrations of cefazolin and chloramphenicol. Ten ophthalmologically healthy dogs receive compounded 5.5% cefazolin or 0.5% chloramphenicol, formulated with either PVA or XHA. Tear samples are collected from 0 to 480 minutes after dosing and quantified by UV–Vis spectrophotometry. XHA yields significantly higher concentrations and exposure (greater AUC0−480), with biphasic kinetics, indicating improved retention for ocular antibiotic delivery.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages7

Reading Time18 min

AccessFree to download

Abstract

Objective

Animals Studied

Procedures

Results

Conclusion

Introduction

Ocular drug delivery with eyedrops

Role of hyaluronic acid and cross-linking

Material and Methods

Animals

Sampling and assay (UV–Vis spectrophotometry)

Veterinary Ophthalmology ORIGINAL REPORT OPEN ACCESS Enhanced Tear Film Concentrations ofCefazolin and Chloramphenicol Using Cross-Linked Hyaluronic Acid in Canine Eyes Dikla Arad | Ella Margot Mordechai | Yulia Goncharov | Ron Ofri | Lionel Sebbag Koret School of Veterinary Medicine, The Hebrew University of Jerusalem, Rehovot, Israel Correspondence: Lionel Sebbag ([lionel.sebbag@mail.huji.ac.il](lionel.sebbag@mail.huji.ac.il)) Received: 4 November 2024 | Revised: 31 December 2024 | Accepted: 25 February 2025 Funding: This work was supported by Sentrx Animal Care (Dômes Pharma Inc.) . Keywords: antibiotic | bacterial keratitis | eye drop | mucoadhesive polymer | pharmacokinetics | tear film ABSTRACT 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. 1 | Introduction Ophthalmic solutions (eyedrops) are the most common formulation for managing ocular diseases in both human and veterinary medicine [1] . Eyedrops offer ease of use, convenience, and high drug levels in the target tissue while minimizing systemic side effects [1] . However, their bioavailability is often limited by ocular barriers (e.g., blood-tear barrier, corneal barrier) and physiological processes like reflex tearing, blinking, and nasolacrimal drainage that rapidly clear the solution to maintain ocular surface homeostasis [1–3] . Recent studies in dogs have demonstrated a 20%–45% decrease in tear film drug levels within 1 min and an 80%–95% decrease by 15 min postadministration [4, 5] . This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2025 The Author(s). Veterinary Ophthalmology published by Wiley Periodicals LLC on behalf of American College of Veterinary Ophthalmologists. Veterinary Ophthalmology, 2026; 29:e70013 1 of 7 [https://doi.org/10.1111/vop.70013](https://doi.org/10.1111/vop.70013) Several strategies can be employed to optimize ocular drug delivery with eyedrops, such as repeated eyedrop administration [6], higher drug concentrations [6], and mucoadhesive polymers to prolong contact time on the ocular surface [7–9] . Hyaluronic acid (HA) i

FAQs

What was the study objective regarding tear film antibiotic concentrations?

To evaluate how 1.4% PVA and 0.75% cross-linked hyaluronic acid affect tear film concentrations of cefazolin and chloramphenicol.

How were drugs formulated and administered in the dogs?

Cefazolin and chloramphenicol were compounded into solutions using either PVA or XHA; each dog received the two antibiotics in opposite randomly assigned eyes, then the experiment was repeated one month later for chloramphenicol formulations.

What were the main findings comparing XHA vs PVA?

Tear film concentrations and overall exposure (AUC0−480) were significantly higher with XHA across most time points, with biphasic kinetics showing an initial decline followed by a slight increase before later reduction.

Sep 28, 2026

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