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Kevin Ward, Koushik Barman, Chinghong Li, Shikha P Barman; Development of a Highly Bioavailable Nanocore-based (OcuSurf™) Ophthalmic Formulation for Treatment of Blepharitis. Invest. Ophthalmol. Vis. Sci. 2018;59(9):230.
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Posterior blepharitis is an eyelid disease primarily of the meibomian glands. Bacteria and chronic inflammation are contributing factors for meibomian gland disease, which leads to ocular surface and tear film alterations. Currently, there is no FDA-approved treatment for blepharitis. A membrane-interactive, biphasic, mucoadhesive delivery system, OcuSurf™, derived from “Ocular Surface”, primarily engineered to rapidly permeate ocular tissues was developed. OcuSurf is liquid-crystalline, with dissolved drug entrapped within the nano-cores. We hypothesized that a combination of a steroid and an antimicrobial (Steroid/ Moxifloxacin Free Base) in this delivery system can be co-encapsulated, leading to a highly bioavailable product to treat both anterior and posterior blepharitis. Steroids were evaluated and included fluticasone propionate (FP), dexamethasone (DX) and loteprednol etabonate (LE). FP was selected due to its high potency and its preference for lipophilic tissues (eyelid). Moxifloxacin Free Base (MX) was used instead of its HCl salt for its high lipophilicity. The meibomian glands are located in the deep fenestrations of the eyelids. Thus, a lipid-based delivery system that is designed to “sink” into the inner and outer eyelids immediately upon instillation is ideal. We hypothesize that the OS-FP/MX can be very effective, with a proposed low dose of the steroid (0.01%) to minimize steroid-induced adverse effects (glaucoma, skin) and 0.5% of Moxifloxacin Free Base. We present characterization data: ex-vivo corneal permeability, in-vitro release, in-vivo irritation and pharmacokinetic tear levels with a single installation.
OS-FP/MX was formulated as per a proprietary process. Permeability studies were performed with freshly excised corneal membranes, using diffusion cells and permeated drug quantitated by HPLC. In-vivo PK studies were performed in rabbit eyes; profiles of FP/MX were collected and analyzed by LC/MS/MS. Irritation assessment of OX-FP/MX was performed in a rabbit model.
The particle size d50 of OS-FP/MX was < 200 nm. High permeation rates of the drug were observed in OS-FP/MX group, in both in-vivo and in-vitro studies. The product was well tolerated in the rabbit eyes.
The rapid release rates both drugs from the nanocores of OS-FP/MX demonstrate feasibility of a highly effective blepharitis product.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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