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Improvement of the Ocular Bioavailability of Econazole Nitrate upon Complexation with Cyclodextrins

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Abstract

Econazole nitrate (EC) is an active, imidazole antifungal agent. However, low aqueous solubility and dissolution rate of EC has discouraged its usage for the treatment of ophthalmic fungal infection. In this study, inclusion complexes of EC with cyclodextrins were prepared to enhance its solubility, dissolution, and ocular bioavailability. To achieve this goal, EC was complexed with β-CyD/HP-β-CyD using kneading, co-precipitation, and freeze-drying techniques. Phase-solubility studies were performed to investigate the complexes in the liquid form. Additionally, the complexes in the solid form were characterized with Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and transmission electron microscopy (TEM). Furthermore, different eye drops containing EC-CyD complexes were prepared using different polymers and then characterized regarding their drug contents, pH, viscosity, mucoadhesive strength, and in vitro release characteristics. The results showed that stable EC-CyD complexes were formed in 1:1 molar ratio as designated by BS-type diagram. Econazole nitrate water solubility was significantly increased in about three- and fourfold for β-CyD and HP-β-CyD, respectively. The results showed that the prepared complexes were spherical in shape having an average particle diameter from 110 to 288.33 nm with entrapment efficiency ranging from 64.24 to 95.27%. DSC investigations showed the formation of real inclusion complexes obtained with co-precipitation technique. From the in vitro studies, all eye drops containing co-precipitate complexes exhibited higher release rate than that of other complexes and followed the diffusion-controlled mechanism. In vivo study proved that eye drops containing EC-CyD complexes showed higher ocular bioavailability than EC alone which indicated by higher AUC, Cmax, and relative bioavailability values.

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Authors and Affiliations

  1. Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, 35516, Mansoura, Egypt

    Abd El-Gawad Helmy Abd El-Gawad, Osama A. Soliman, Marwa S. El-Dahan & Saeed A. S. Al-Zuhairy

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  1. Abd El-Gawad Helmy Abd El-Gawad
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  2. Osama A. Soliman
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  3. Marwa S. El-Dahan
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  4. Saeed A. S. Al-Zuhairy
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Correspondence to Abd El-Gawad Helmy Abd El-Gawad.

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The animal experimental procedures conform to the ethical principles of the scientific committee of the Pharmacy Faculty, Mansoura University, Egypt (code number, 2016–9).

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The authors declare that they have no conflict of interest.

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Abd El-Gawad, A.EG.H., Soliman, O.A., El-Dahan, M.S. et al. Improvement of the Ocular Bioavailability of Econazole Nitrate upon Complexation with Cyclodextrins. AAPS PharmSciTech 18, 1795–1809 (2017). https://doi.org/10.1208/s12249-016-0609-9

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