Development and Ex Vivo Evaluation of Famciclovir Ocular Inserts: Physicochemical Characterization and Biodistribution in Rabbit and Porcine Models

Famciclovir is a potent antiviral with superior bioavailability compared to conventional treatments for herpes zoster. However, addressing ocular viral infections remains challenging due to limited direct therapeutic options. Here we describe the development and characterization of famciclovir ocular inserts and evaluate their ex vivo diffusion in rabbit eyes and biodistribution in rabbit and porcine models, comparing interspecies drug retention. Inserts were designed and characterized using various polymers (polyvinyl alcohol, chitosan, sodium alginate and polyvinylpyrrolidone). Physicochemical and mechanical properties, hygroscopicity, water loss, drug release kinetics and ocular tolerability (Hen’s Egg Test–Chorioallantoic Membrane (HET-CAM)) were evaluated. Ex vivo diffusion studies were conducted in rabbits’ eyes comparing drug penetration and retention between the most promising inserts with a conventional famciclovir solution. Subsequently, biodistribution assays were performed comparing drug retention in ocular tissues in both animal models. Inserts formulated with a homogeneous polyvinyl alcohol and polyvinylpyrrolidone blend showed optimal transparency, softness and structural uniformity. They exhibited physiological pH, low weight (7.81 ± 0.48 mg) and thickness (0.10 ± 0.01 mm), adequate elongation percentage (30.70 ± 7.30 %) and sustained famciclovir release for 8 hours, without causing irritation. In ex vivo assays, the solution showed higher transcorneal and transscleral diffusion (75.67 ± 2.27 μg/cm 2 and 162.47 ± 47.21 μg/cm 2 respectively), whereas inserts achieved significantly higher drug retention, particularly in the cornea (48.19 ± 8.18%), the primary site of herpes zoster ophthalmicus infection. Biodistribution profiles were comparable between rabbits and pigs, suggesting similar ex vivo behavior. These findings demonstrate promising ex vivo performance of famciclovir ocular inserts for sustained drug delivery, although further in vivo studies are required. • Polymer-based ocular inserts were developed for controlled famciclovir delivery • Ex vivo diffusion studies showed increased drug retention in the cornea • Porcine and rabbit models showed comparable ocular biodistribution profiles • Ocular inserts showed improved biodistribution compared with the solution