Comparison of the In Vitro Tolerance and In Vivo Efficacy of Traditional Timolol Maleate Eye Drops versus New Formulations with Bioadhesive Polymers

Abstract

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.

Self-Assembling Elastin-Like Hydrogels for Timolol Delivery: Development of an Ophthalmic Formulation Against Glaucoma

“…As shown in Figure 7, formulations containing TM produced a decrease in the IOP, with no statistical differences being detected between them in the first three hours. However, this situation changed at 4 h post-administration, when the IOP for eyes treated with the formulation lacking recombinamer was statistically significantly higher than that displayed by the eyes 42 , it is important to note that the hypotensive effect achieved by the formulation containing (EIS)x2 was achieved without the use of preservatives. The inclusion of preservatives, such as benzalkonium chloride, 43 is believed to favor TM penetration, and therefore its therapeutic efficacy, due to disruption of the hydrophobic barrier of the corneal epithelium.…”

Gelatin Nanoparticles-HPMC Hybrid System for Effective Ocular Topical Administration of Antihypertensive Agents

“…An effective method to retain the formulation on the ocular surface is the addition of polymers able to increase the formulation viscosity and/or its mucoadhesion, such as gelatin, chitosan, hydroxypropyl methylcellulose (HPMC), gellan, carboxy methylcellulose (CMC), hyaluronic acid, polyacrylate acids, and xanthan gums among others. This strategy partially avoids the ocular surface clearance produced by the tearing and blinking reflex [24][25][26][27][28]. In fact, several authors have successfully explored the use of the polysaccharide HPMC in this context [29][30][31].…”

Enhancement and inhibition effects on the corneal permeability of timolol maleate: Polymers, cyclodextrins and chelating agents

“…However, the bioavailability of ophthalmic drugs is very poor due to the effective protective mechanisms of the eye (Lee and Robinson, 1986), including blinking, lachrymation, and drainage (Ludwig, 2005). Therefore, frequent instillations of eye drops or high drug concentrations are needed to achieve therapeutic levels in the tissues (Andrés-Guerrero et al, 2011), which might induce toxic side effects and cellular damage at the ocular surface (Baudouin, 1996). In addition, the treatment of certain ocular diseases such as glaucoma follows the administration of combinations of two or more drugs (Bell et al, 2010), and therapies must be continued throughout the lifetime of the patient (Andrés-Guerrero, 2011), leading to a lack of patient's compliance.…”

“…Therefore it is necessary to deepen research into new mechanisms focused on increasing the bioavailability of timolol at the ocular surface. In this regard, the use of bioadhesive polymers has been proposed as components of antiglaucoma formulations to reduce ocular toxicity, improve drug efficacy, and protect the ocular surface in long-term therapies (Andrés-Guerrero, 2011). Both the ability to increase the formulation viscosity (Saettone et al, 1982) and the bioadhesive properties (Kaur and Smitha, 2002) of polymers were reported to reduce the drainage after instillation and therefore, increase the therapeutic efficacy of the ophthalmic drugs.…”