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Peter Jarrett, Rami Elhayek, Sarah Guedez, Amar Sawhney; Examination of in vitro release profiles of bromfenac, diclofenac and nepafenac as drug candidates for sustained release NSAID punctum plug. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1099.
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To examine the in vitro release profiles of three nonsteroidal anti-inflammatory drugs (NSAIDs): Bromfenac (BFc), Diclofenac (DFc) and Nepafenac (NFc) from polyethylene glycol (PEG) hydrogel punctum plugs.
BFc, DFc and NFc were each suspended with equal loading in a multi-arm PEG solution and injected into small diameter silicone tubing prior to cross-linking. The hydrogel NSAID matrix confined within the silicone tubing was cut to 5mm plugs. The NSAID release profile was determined in PBS pH7.4 at 37°C simulating the release from a punctum plug (PP) inserted in the canaliculus. The release media was sampled and exchanged daily. Plugs were removed for photographic imaging to track the release of the drug qualitatively indicated by drug clearance from both ends of the plug. Percent drug release was determined using UV/Vis spectrophotometry.
As shown in Figure 1, each NSAID was released from the plug at a rate relative to their aqueous solubility (BFc, DFc and NFc having a water solubility of 53, 0.6 and 0.006 mg/mL respectively). The most soluble BFc was released in 7 days, DFc was released in 14 days, and the least soluble NFc’s projected release was calculated at approximately 120 days. Images of a DFc-loaded hydrogel plug showing drug clearance over time are included within Figure 2.
BFc, DFc and NFc each showed variable rates of sustained release from a PEG hydrogel plug corresponding to their water solubility. Solubility modifiers and/or modifications to the PEG hydrogel matrix can be employed to tailor the release profile of BFc, DFc and NFc, depending on the drug load and duration of therapy required. Topical NSAIDs, such as BFc, DFc and NFc are used to treat post-surgical inflammation as well as various ophthalmic conditions, and typically require multiple daily dose administrations over extended periods of time. A single dose NSAID punctum plug may provide more consistent dosing while eliminating issues of patient non-compliance.
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