A Gel-Free Reservoir System for Once-a-Day Ophthalmic Delivery of Timolol Maleate

Purpose This study aims to formulate an ophthalmic gel-free reservoir (GFR) system for once-a-day (OD) delivery of timolol maleate for the treatment of glaucoma. Methods The GFR system contains hydroxypropyl methylcellulose and polyvinylpyrrolidone mixed in ratios, HPMC conc /PVP conc = 0.1 to 2.0 with a total polymer concentration of ~ 1.0–4.0% providing a viscosity of ~ 30–65 cps. A formulation of timolol maleate was prepared by combining buffers (borate) and preservative cations (Zn +2 ) with GFR to form an anionic polymer interpenetrating network (IPN) which obstructs the diffusion of the cationic timolol maleate, thus providing sustained action. Results The GFR composition was optimized to impart physicochemical properties that were similar to artificial tear fluid, including clarity, with optical transmission of > 95%, adjusted osmolality of ~ 300 mOsmol, pH range of 6.5–7.5, surface tension of 35–42 mN/s, and 40–45 mPas viscosity for ocular retention and retarding lacrimal drainage. The mucoadhesive index of ~ 9.0 which was more than conventional timolol maleate eye drops further helped in eye drop retention. The solution was weakly pseudoplastic having a calculated blink viscosity of