Once Daily Pregabalin Eye Drops for Management of Glaucoma

Elevated intraocular pressure (IOP) is the most significant risk factor contributing to visual field loss in glaucoma. Unfortunately, the deficiencies associated with current therapies have resulted in reduced efficacy, several daily dosings and poor patient compliance. Previously, we identified the calcium voltage-gated channel auxiliary subunit alpha2delta 1 gene (Cacna2d1) as a novel modulator of IOP and demonstrated that pregabalin, a drug with high affinity and selectivity for CACNA2D1, lowered IOP in a dose-dependent manner. Unfortunately, IOP returned to baseline at six hours after dosing. In the current study, we develop a once daily topical pregabalin-loaded multiple water-in-oil-in-water microemulsion formulation to improve drug efficacy. We characterized our formulations using multiple in vitro and in vivo evaluations. Our lead formulation provides continuous release of pregabalin for up to 24h. Because of its miniscule droplet size (<20nm), our microemulsion has a transparent appearance and sh...