Sustained release ocular inserts of brimonidine tartrate for better treatment in open-angle glaucoma

Pathology of eye, especially in the case of glaucoma, requires optimal therapeutically effective concentration of the drug in the ocular tissues for prolonged period of time with decreased dosing frequency and improved patient compliance. In the present study, brimonidine tartrate (BRT) ocular inserts were designed based on hydrophilic and/or inert/zwitterionic polymer matrix to design mucoadhesive and extended release ocular inserts. Designed inserts were evaluated for their physicochemical properties such as crushing strength/hardness, friability, drug content and mucoadhesion, and erosion and in vitro drug release characteristics. The selected optimised formulations were compared with marketed preparation for in vivo ocular irritation in healthy rabbits and for in vivo pharmacodynamic efficacy on alpha-chymotrypsin-induced glaucomatous rabbits. The developed formulations showed good physicochemical properties and mucoadhesive strength, and a good correlation was seen between rate of erosion or swelling with drug release rate in case of formulations with higher proportion of polyethylene oxide (PEO). Modulation of drug release was achieved by incorporating Eudragit in PEO matrix. Addition of Eudragit resulted in shifting of drug release mechanism from erosion-controlled to diffusion-controlled mechanism. In vivo ocular irritation studies confirmed the absence of any irritation upon administration in rabbits. Intraocular pressure (IOP) measurement studies showed an improved IOP-lowering ability of ocular insert of BRT in comparison to eye drops.