Abstract
Purpose :
Antibiotic-loaded ocular inserts can address challenges in drug delivery and overcome limitations of eye drops use. The aim of this in vitro study was to optimise a sustained ocular drug delivery system for levofloxacin (LFX), a broad-spectrum antibiotic commonly used for external ocular infections.
Methods :
Inserts were prepared by a refined quality by design solvent casting procedure, using 0.2%, 0.5% and 1.0% concentrations of LFX solutions with hypromellose, sodium alginate, gelatin and PEG400. Formulations were characterised for physicochemical properties: uniformity of mass and thickness, loss on dryness, moisture absorption, and surface pH. Mechanical properties were assessed and compared against a marketed buccal film, as no ocular formulation was available. Inserts’ uniformity of drug content and release profile were assessed by validated analytical method. The effect of LFX fractions released over time on growth dynamics of Staphylococcus Aureus and Pseudomonas Aeruginosa was studied to evaluate extended antimicrobial efficacy.
Results :
The optimised formulation including hypromellose (5%), sodium alginate (3%), gelatin (1%), PEG 400 (10%), and prepared with 0.5% LFX solution, resulted in inserts holding good physicochemical properties, in line with eye characteristics. Inserts mass (11.1 ± 0.3 mg), thickness (160 ± 10 µm) and LFX content (232.8 ± 4.4 µg) were found consistent and complying with International Pharmacopoeia guidelines. Inserts withstood unilinar (elongation at max load 25.5 ± 1.9%) and repeated (foldability > 300 times) mechanical stresses, suggesting suitability to manipulation linked to eye administration. The release pattern of 0.5% LFX showed that half of drug content was released within the first 30 minutes, indicating immediate effectiveness of inserts against bacteria, with the remaining LFX released in 24 hours. Kinetic growth assays indicated that the fractions of LFX released within the 24 hours testing period were adequate to prevent Staph. Aureus and P. Aeruginosa growth.
Conclusions :
The new LFX-loaded inserts exhibited good physicochemical and mechanical properties, indicating compatibility with ocular anatomophysiology and administration procedure. LFX content and release pattern showed immediate and sustained antimicrobial efficacy of inserts on bacterial growth.
Current research is focusing on formulation cytotoxicity and transepithelial drug permeability.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.