Influence of the test method on in vitro drug release from intravitreal model implants containing dexamethasone or fluorescein sodium in poly (d,l-lactide-co-glycolide) or polycaprolactone

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Abstract

Sustained intravitreal dexamethasone (DX) administration with the FDA and EMA approved Ozurdex® implant is indicated for the treatment of macular edema and non-infectious uveitis. Since drug release after intravitreal application cannot be determined in vivo in human eyes, the characterization of drug release in vitro in addition to animal models is of great importance. The aim of this study was to provide information about the influence of the test method on the in vitro drug release from intravitreal model implants. The following test methods were used: a shaking incubator experiment in reagent tubes, the small volume USP apparatus 7, the Vitreous Model (VM) and a system simulating the impact of movement on the VM (Eye Movement System, EyeMoS). Cylindrical model implants composed of DX and PLGA (poly (d,l-lactide-co-glycolide)) and additional polycaprolactone (PCL) implants containing fluorescein sodium (FS) as a model substance were produced by hot melt extrusion and were cut to a length of approximately 6 mm. Drug release was studied in ringer buffer pH 7.4 and in a modified polyacrylamide gel (PAAG) as vitreous substitute. In combination with the VM, the shape, the gel structure and a partial liquefaction (50%) were simulated in vitro.

Swelling, disintegration, fragmentation, surface enlargement and changes in shape of the PLGA model implants were observed during the drug release study. We experienced that not each of the test methods and media were suitable for drug release studies of the PLGA implants. Marked differences in the release profiles were observed depending on the employed test method. These results emphasize the necessity to understand the underlying in vivo processes and to transfer the knowledge about the release determining factors into reliable in vitro test systems.

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