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Publications

Journal Article Ppublish

PubMed: 40113103 DOI: 10.1016/j.ejps.2025.107077

Overcoming barriers in formulating practically insoluble loteprednol etabonate in ophthalmic nanoemulsion.

Eur J Pharm Sci 209:107077

Authors: Josip Ljubica, Bisera Jurišić Dukovski, Iva Krtalić, Marina Juretić, Maša Sufundžić Kučuk, Igor Petriček, Drago Špoljarić, Luka Bočkor, Petra Kocbek, Anita Hafner, Ivan Pepić, Jasmina Lovrić

Affiliations

  • University of Zagreb Faculty of Pharmacy and Biochemistry, Ante Kovačića 1, 10000 Zagreb, Croatia.
  • University of Zagreb Faculty of Pharmacy and Biochemistry, Ante Kovačića 1, 10000 Zagreb, Croatia; PLIVA Croatia Ltd, TEVA Member Group, Baruna Filipovića 25, 10000 Zagreb, Croatia.
  • PLIVA Croatia Ltd, TEVA Member Group, Baruna Filipovića 25, 10000 Zagreb, Croatia.
  • Jadran-galenski laboratorij d.d. Svilno 20, 51000 Rijeka, Croatia.
  • University Hospital Centre Zagreb, Mije Kišpatića 12, 10000 Zagreb, Croatia.
  • Visage Technologies d.o.o. Ul. Ivana Lučića 2a, 10000 Zagreb, Croatia.
  • Institute for Anthropological Research, Gajeva ul. 32, 10000 Zagreb, Croatia.
  • University of Ljubljana, Faculty of Pharmacy, Aškerčeva cesta 7, 1000 Ljubljana, Slovenia.
  • University of Zagreb Faculty of Pharmacy and Biochemistry, Ante Kovačića 1, 10000 Zagreb, Croatia.

Abstract

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.

MeSH

Pharmaceutical Preparations, Adrenal Cortex Hormones, Chemistry, Pharmaceutical, Signs And Symptoms, Epithelium, Corneal, Technology, Pharmaceutical, Retention, Psychology, Loteprednol Etabonate, Epithelium, Absorption, Pharmacokinetics