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Preparation and Evaluation of Cubosomes/Cubosomal Gels for Ocular Delivery of Beclomethasone Dipropionate for Management of Uveitis

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Abstract

Purpose

Topical corticosteroids administration is commonly used for management of various ocular conditions especially those affecting the anterior segment of the eye. Poor solubility and limited pre-corneal residence time result in insufficient drug penetration to the outer (cornea and conjunctival-scleral) coats of the eye. This study aimed to prepare and evaluate cubosomes for prolonging residence time and enhancing ocular bioavailability of BDP.

Methods

GMO-cubosomes were prepared using the top-down technique. Two stabilizers were investigated: poloxamer 407 and solulan C24. Particle size, EE %, polarized-light microscopy, TEM, in vitro release, transcorneal permeation, BCOP, histopathology and in vivo evaluation for treatment of uveitis in a rabbits’ model were studied.

Results

The prepared cubosomes were of nano-sizes (100 nm – 278 nm); EE% was around 94%. The cubosomes were confirmed by visualizing the “Maltese crosses” textures. Transcorneal permeation was significantly (p < 0.05) improved, compared to BDP-suspension (the control formulation). The optimized cubosomes F1P was incorporated in CMC gel (Cubo-gel). The prepared Cubo-gel formulations showed better rheological characteristics and high ocular tolerability. Superior anti-inflammatory properties were recorded for the Cubo-gel for treatment of endotoxin-induced uveitis in the rabbit model when compared to the control BDP-suspension.

Conclusions

Transcorneal permeation parameters Papp and flux and AUC0-10h markedly enhanced by up to 4-, 5.8-and 5.5-fold respectively, compared to the control BDP-suspension formulation. This study suggested that cubosomes/Cubo-gel could be an auspicious ocular delivery system for BDP that was able to effectively treat uveitis (a disease of the posterior segment of the eye).

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Abbreviations

AUC:

Area under the curve

BCOP:

Bovine corneal opacity and permeability assay

BDP:

Beclomethasone dipropionate

CMC:

Carboxymethylcellulose

EE%:

Entrapment efficiency percentage

GMO:

Glyceryl monooleate

Papp :

Apparent permeability coefficient

TEM:

Transmission electron microscopy

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Authors and Affiliations

  1. Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, Egypt

    Sherif A. Gaballa, Omar H. El Garhy & Hamdy Abdelkader

  2. Department of Ophthalmology, Faculty of Medicine, Minia University, Minia, Egypt

    Hossam Moharram

  3. Pharmaceutics Department, Faculty of Pharmacy, Deraya University, New Minia City, Minia, Egypt

    Hamdy Abdelkader

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  1. Sherif A. Gaballa
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  3. Hossam Moharram
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  4. Hamdy Abdelkader
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Correspondence to Hamdy Abdelkader.

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Gaballa, S.A., El Garhy, O.H., Moharram, H. et al. Preparation and Evaluation of Cubosomes/Cubosomal Gels for Ocular Delivery of Beclomethasone Dipropionate for Management of Uveitis. Pharm Res 37, 198 (2020). https://doi.org/10.1007/s11095-020-02857-1

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