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H. Guo, J. Chen, G. Cynkowska, T. Cynkowski, S. Deokule; Development of Bioerodible Sustained Release Brimonidine Intraocular Device. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3165. doi: https://doi.org/.
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The purpose of this project was to design and develop a sustained release intraocular device providing release of brimonidine for over 3 months with a targeted release rate of approximately 0.4µg/day.
In-vitro:Brimonidine was mixed with 10% polyvinyl alcohol and granulated. The wet granulation was filled into a 25 gauge bioerodible polymer tube and air dried. A rate controlling membrane was applied to the open ends and heat cured to provide the desired permeability. In-vitro release was determined by immersion on phosphate buffered solution (pH 7.4) buffer at 37oC and samples were taken periodically. The buffer was regularly replaced to maintain sink conditions. Drug release was determined by HPLC and was calculated from cumulative release versus time.In-vivo:Drug impregnated devices were injected into the vitreous cavity of one eye of 4 New Zealand pigmented rabbits using 25 gauge needle. Other eye of each animal was injected with sham implant. Animals were euthanized at 1 month, and vitreous and aqueous drug levels were determined by HPLC. In vitro release was again measured and residual drug determined from devices that were retrieved from the rabbit eyes.
In-vitro testing demostrated that after an initial burst of 1.2 ug/day of drug over 20 days, the release of brimonodine from the device closely followed zero-order kinetics with a rate of 0.4µg/day over 3 months. At 4 months devices were 95% depleted. Release rates from devices retrieved from rabbit eyes and residual drug analysis indicted in-vivo release was within 10% of in-vitro release. One month after implantation the vitreous concentration was about 40 ng/ml, which is comparable with aqueous levels observed in humans one hour after topical brimonidine application (60ng/ml).
Long term intraocular sustained release of brimonidine is achievable with these systems, additional in-vivo evaluation will provide evidence of safety and efficacy.
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