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  • Title: Ophthalmic Econazole Hydrogels for the Treatment of Fungal Keratitis.
    Author: Díaz-Tomé V, Luaces-Rodríguez A, Silva-Rodríguez J, Blanco-Dorado S, García-Quintanilla L, Llovo-Taboada J, Blanco-Méndez J, García-Otero X, Varela-Fernández R, Herranz M, Gil-Martínez M, Lamas MJ, González-Barcia M, Otero-Espinar FJ, Fernández-Ferreiro A.
    Journal: J Pharm Sci; 2018 May; 107(5):1342-1351. PubMed ID: 29305870.
    Abstract:
    Econazole is a feasible alternative treatment in the management of fungal keratitis. Nevertheless, its low water solubility is considered the main limitation to the incorporation into ophthalmic formulations. In this work, econazole nitrate is solubilized by using cyclodextrins to achieve an optimum therapeutic concentration. Phase solubility diagrams suggest α-cyclodextrin as the most effective cyclodextrin and later the inclusion complex formed with this one was characterized in solution by 1D, 2D-NMR, and molecular modeling. Econazole-α-cyclodextrin inclusion complex was included in 2 types of ocular hydrogels: a natural polysaccharides ion-sensitive hydrogel and a hyaluronic acid hydrogel. Both of them show no ocular irritation in the hen's egg test on chorioallantoic membrane assay and a controlled econazole release over time. Permeability studies suggest that hydrogels do not modify the econazole nitrate permeability through bovine cornea in comparison with an econazole-α-cyclodextrin inclusion complex solution. Finally, ocular biopermanence studies performed using positron emission tomography show these hydrogels present a high retention time on the eye. Results suggest the developed formulations have a high potential as vehicles for the econazole topical ocular administration as fungal keratitis treatment.
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