Examination of in vitro release profiles of bromfenac, diclofenac and
nepafenac as drug candidates for sustained release NSAID punctum plug
Author Block: P. Jarrett, R. El-Hayek, S. Guedez, A. Sawhney. All of Ocular Therapeutix, Inc.,
Bedford, MA
Purpose: 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.
Methods: 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.
Results: 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.
Conclusions: 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.