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Kevin L Ward, Kathryn S Crawford, Moli Liu, Anne-Marie L Cromwick, Shikha P Barman; A Novel Biocompatible, Membrane-Interactive Delivery System for Administration of an Ophthalmic Anti-inflammatory Drug. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4031.
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© ARVO (1962-2015); The Authors (2016-present)
The majority of ophthalmic eye-drops utilize insoluble active pharmaceutical ingredients; thus, they exist as drug suspensions. For drug suspensions to absorb, they need to dissolve first. In the ocular space, rapid fluid turnover and loss via the naso-lacrimal duct results in just 5% of the drug being absorbed. Thus, clinical need exists for a pharmaceutically-compliant drug delivery system that can rapidly permeate and adhere to tissues for enhanced bioavailability and enhanced duration.We present a membrane-interactive, biphasic, mucoadhesive delivery system, OcuSurf™, derived from “Ocular Surface”, primarily engineered to rapidly permeate ocular tissues. The delivery system is liquid-crystalline, with high concentrations of dissolved drug designed to rapidly permeate corneal tissue, requiring less drug to generate a therapeutic response. We present comparative in-vitro corneal permeability studies between three formulations using fluticasone propionate (FP) as a steroid to be used as an anti-inflammatory drug post cataract surgery. Formulation 1 was a micronized suspension of size similar to most ophthalmic suspensions (d50 between 2-3 microns), Formulation 2 was a nanoized suspension of sub-micron size (0.200 microns) and Formulation 3 was the OcuSurf nanostructured drug-containing emulsion of size (0.198 microns). In-vivo pharmacokinetics of OcuSurf-FP shows rapid drug uptake by corneal tissues.
Permeability studies were performed through freshly excised corneal membranes, using Franz-type diffusion cells and permeated drug quantitated by HPLC. In-vivo pharmacokinetic studies were performed in a rabbit model; profiles were collected and analyzed by LC/MS/MS. Irritation assessment of the OcuSurf cohort was performed in a rabbit model, using a Draize grading scale.
High permeation rates of the drug were observed in the OcuSurf-FP cohort, in both in-vivo and in-vitro studies. In contrast, FP permeation rates were many-fold lower in the microsuspension and nanosuspension cohorts. OcuSurf-FP eye-drops were well tolerated in rabbit eye, with twice-daily dosing over 3 days. Furthermore, drug clearance rates were slower in the OcuSurf-FP group.
The OcuSurf delivery system provides enhancement to bioavailability of drugs by rapid absorption into tissues.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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