Overcoming barriers in formulating practically insoluble loteprednol etabonate in ophthalmic nanoemulsion

Scientific paper - Original scientific paper

• Author: Josip Ljubica
• Author: Bisera Jurišić Dukovski
• Author: Iva Krtalić
• Author: Marina Juretić
• Author: Maša Safundžić Kučuk
• Author: Igor Petriček
• Author: Drago Špoljarić
• Author: Luka Bočkor
• Author: Petra Kocbek
• Author: Anita Hafner
• Author: Ivan Pepić
• Author: Jasmina Lovrić
• Author's institution: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmaceutical technology)
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract (english)

Loteprednol etabonate (LE) is a soft corticosteroid recently approved for the short-term treatment of signs and symptoms of dry eye disease. LE is available on the market as a suspension, which can release only limited amount of dissolved corticosteroid after application at the ocular surface. This study is focused on the development of an oil-in-water nanoemulsion (NE) to effectively deliver dissolved LE to the ocular surface, in order to promote its absorption. We newly developed an extended-throughput 3D model of the corneal epithelium for biocompatibility study, and an innovative approach to investigate the effect of biorelevant dilution on LE release from the NE oil phase. Castor oil, Capryol® 90, Kolliphor® EL and Soluplus® were selected as NE excipients based on their potential to dissolve LE. Design of experiments was successfully employed to develop biocompatible and physically stable NE with high LE content (0.15 %, w/w) and retention efficiency (87 % after 10 months of storage at room temperature). LE retention within oil droplets (above 90 % of the initial LE content) despite biorelevant dilution simulating tear turnover suggests the potential for direct LE absorption from the NE oil droplets into the lipophilic corneal epithelium. The results obtained encourage the extension of the studies in terms of in vitro permeability and in vivo eye-related bioavailability assessment to prove the potential of the proposed LE formulation.

• Keywords (english): eye drops; dry eye disease; corticosteroid; nanoemulsion; 3D HCE-T model; In vitro release
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review - international
• Publication version: Published version
• Journal title: European Journal of Pharmaceutical Sciences
• Numbering: vol. 209, 107077
• p-ISSN: 0928-0987
• DOI: https://doi.org/10.1016/j.ejps.2025.107077
• URN:NBN: urn:nbn:hr:163:299551
• Publication: 2025-03-18
• Project: Number: IP-2019-04-2174; Title (croatian): Nanoemulzije unaprijeđene biofarmaceutske vrijednosti za liječenje bolesti suhoga oka; Title (english): Biopharmaceutically improved nanoemulsions for the treatment of dry eye disease; Acronym: BeatDED; Leader: Jasmina Lovrić; Jurisdiction: Croatia; Funding stream: Research Projects
• Document URL: https://www.sciencedirect.com/science/article/pii/S0928098725000764?via%3Dihub
• Type of resource: Text
• Access conditions: Open access
• Created on: 2025-03-26 10:39:30