OCULAR MINI-TABLETS FOR CONTROLLED-RELEASE OF TIMOLOL - EVALUATION INRABBITS

Topical delivery of timolol by inserts or similar controlled-release d evices may offer distinct advantages over administration by eyedrops. The purpose of this investigation was the evaluation in rabbits of oph thalmic inserts (denominated mini-tablets, MT) for sustained/controlle d release of timolol maleate (TiM). The MTs (diameter 3.5 mm, thicknes s 1.5 mm, average TiM content 0.34 or 0.68 mg) were prepared by compre ssing appropriate mixtures of powders with a standard tabletting machi ne. A thin, rate-controlling membrane was applied over the devices by spraying aqueous dispersions of acrylic copolymers. A first series of different (uncoated and coated) MTs were tested for release of TiM to the lacrimal fluid, using commercial eyedrops (Timoptol(R) 0.5%) as a reference standard. Two MTs (one of which was coated) and the same ref erence solution were then selected for an ocular absorption study. Ana lysis of TiM in the aqueous humor indicated that the coated MT was cap able of maintaining low and steady levels of TiM for at least 19 h, wh ile the other device, identical but uncoated, produced a prolonged-pul se effect lasting about 8 h. The apparent mean residence time (MRT) of TiM in the aqueous humor was 1.3 h for the reference solution, 3.2 h for the uncoated MT, and 5.7 h for the coated one. The present prelimi nary results point to the potential validity of coated mini-tablets as simple systems for controlled ocular delivery of timolol.