Development and evaluation of ocular antibiotic-loaded soluble film inserts

Abstract

Antibiotic eyedrops typically require frequent instillation due to the eye’s defensive mechanisms limiting drugs from reaching target sites. This may risk patient non-adherence and treatment inefficacy. The aim of this study was to develop a biocompatible and fully soluble ocular film insert to enhance the delivery of levofloxacin, as well as the handling procedure for its administration; based on the anatomical dimensions and physiological conditions of the human eye.

Inserts were prepared by solvent casting method, using HPMC, sodium alginate, gelatin, PEG 400, and levofloxacin solution, and characterised for various physicochemical properties (e.g., uniformity of weight and thickness, loss on dryness, swelling index, water uptake and surface pH). Mechanical properties were assessed and compared against a commercially available buccal film formulation. Uniformity of content and release profile of inserts were assessed by means of a validated analytical method. Antibacterial effectiveness was studied by adapted disc diffusion method on Staphylococcus aureus and Pseudomonas aeruginosa.

The formulation including HPMC E15 (1250 mg), low viscosity sodium alginate (750 mg), type A gelatin (250 mg) and PEG 400 (2.5 mL) and 0.1% levofloxacin solution, resulted in high quality inserts, exhibiting uniformity of mass, thickness, and levofloxacin content, that comply with Pharmacopeial standards. Inserts were able to withstand unilinear and repeated mechanical stresses, suggesting suitability for manipulation linked to eye administration. The fully soluble levofloxacin-loaded inserts exhibited good physicochemical and mechanical characteristics, indicating good compatibility with ocular environment and administration procedure. Consistent levofloxacin content and biphasic release pattern showed immediate and sustained antimicrobial efficacy, consistently above the minimum inhibitory concentrations for the model species tested. This work also presents an experimental framework that can be adapted for designing and testing ocular drug delivery systems accounting for anatomical and physiological characteristics of the eye.

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Materials

Levofloxacin (98.0–102.0% anhydrous basis, HPLC grade), gelatin (from porcine skin, Type A), alginic acid sodium salt from brown algae (low and medium viscosities), polyethylene glycol (PEG) 400 (BioUltra), and glycerol (BioXtra ≥ 99%), as well as tryptic soy broth, sodium chloride, sodium bicarbonate, potassium chloride and calcium chloride were obtained from Sigma Aldrich (Gillingham, UK). HPMC E15 was purchased from JRS PHARMA (Rosenberg, Germany). Methocel™ E6, K4M and K100M were generously gifted from Colorcon (Dartford, UK). Setofilm (4 mg, orodispersible) was purchased from AAH Pharmaceuticals (Coventry, UK). Liquid chromatography reagents were purchased from Fisherbrand™ (Loughborough, UK). All reagents were used as received. Water was distilled with Purite Select Ondeo distiller.

Alfredo Desiato, Affiong Iyire, Gurpreet Bhogal-Bhamra, Shehzad A. Naroo, Raquel Gil-Cazorla, Development and evaluation of ocular antibiotic-loaded soluble film inserts, Contact Lens and Anterior Eye, 2024, 102352, ISSN 1367-0484, https://doi.org/10.1016/j.clae.2024.102352.