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®, BAK-preserved Timoftol® and BAK-preserved Timolol Sandoz®.
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.
In all cases, cell survival following exposure to the formulations was greater in the new unpreserved TM formulations than in the traditional TM solutions (BAK-preserved and unpreserved). Additionally, the new formulations were demonstrated to maintain the hypotensive effect of TM in different magnitudes. The maximal hypotensive effect was reached by TM 0.5% in carboxymethyl cellulose 0.5% (32.37%).
We demonstrated that new unpreserved formulations of TM with bioadhesive polymers were able to decrease IOP in rabbits and reach values closer to 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 proposed to be part of antiglaucoma formulations to reduce ocular toxicity, improve drug efficacy and protect the ocular surface in long term therapies.
Invest Ophthalmol Vis Sci. 2011 Feb 4. [Epub ahead of print]
Andrés-Guerrero V, Vicario-de-la-Torre M, Molina-Martínez IT, Benítez-Del-Castillo JM, García-Feijoo J, Herrero-Vanrell R.
Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Complutense University, 28040 Madrid, Spain.