Comparison of the in vitro tolerance and in vivo efficacy of traditional timolol maleate eye drops versus new formulations with bioadhesive polymers

Abstract

PURPOSE. To assess the in vitro tolerance and in vivo efficacy of new unpreserved formulations of timolol maleate (TM) in aqueous solutions of bioadhesive polymers used for dry eye treatment and to compare them with three traditional TM formulations: unpreserved Timabak (Thea, Madrid, Spain), benzalkonium chloride (BAK)-preserved Timoftol (Frosst Laboratories, Madrid, Spain), and BAK-preserved Timolol Sandoz (Frosst Laboratories).

METHODS. New formulations were composed of TM (0.5%) and carboxymethyl cellulose (0.5%), hyaluronic acid (0.2%), or hydroxypropylmethyl cellulose (0.3% or 0.5%). In vitro tolerance was determined in human corneal-limbal epithelial cells and normal human conjunctival cells. The ocular hypotensive effect was evaluated measuring IOP in rabbit eyes for 8 hours.

RESULTS. In all cases, cell survival after exposure to the formulations was greater in the new unpreserved TM formulations than in the traditional TM solutions (BAK-preserved and unpreserved). In addition, the new formulations were demonstrated to maintain the hypotensive effect of TM in different magnitudes. The maximum hypotensive effect was reached by TM 0.5% in carboxymethyl cellulose 0.5% (32.37%).

CONCLUSIONS. The results demonstrated that new unpreserved formulations of TM with bioadhesive polymers decreased IOP in rabbits and reached values closer to those reached by traditional solutions. Furthermore, new formulations presented a significantly higher in vitro tolerance than the same compound in traditional formulations. Although unpreserved formulations are usually more expensive, preservative-free antiglaucoma eye drops should improve compliance and adherence in the medical treatment of glaucoma. Bioadhesive polymers could be part of antiglaucoma formulations to reduce ocular toxicity, improve drug efficacy, and protect the ocular surface in long-term therapies.