Ophthalmic suspension of Brimonidine for sustained delivery using nano-resin/drug complex technique

Abstract

Brimonidine is used to lower intraocular pressure (IOP) in glaucoma patients. An ophthalmic Brimonidine formulation was developed to reduce the dosing frequency from three times a day to once a day using a drug/nanoresin complex suspension. Cationic Brimonidine forms complex with Amberlite™ IRP69 resin in an aqueous medium. The resin was milled to nanosize range and characterized for simulated mucous interaction and drug complexation. The drug/nanoresin complex was amorphous and showed ion-triggered release of Brimonidine in presence of tear salts. Nano-resin/drug ophthalmic suspension of 0.35% strength was formulated with excipients that did not interfere with drug/nanoresin complexation. The Brimonidine ophthalmic suspension had a pH value of 6.8–7.2, viscosity value ∼40–80cps, osmolality ∼280–350 mOsm/kg, D50 of 0.190 μm and complied with pharmacopoeial antimicrobial efficacy test. In-vitro release of Brimonidine from nano-resin complex formulation was slower in water than simulated tear fluid. The suspension was stable for 18 months at room temperature. In-vivo animal study showed comparable efficacy of once a day 0.35% nano-resin formulation to three times a day 0.15% solution formulation. There was improved absorption of the drug in aqueous humor which translated to a significantly high peak IOP reduction for a sustained period.