Polysaccharides as Excipients for Ocular Topical Formulations

Abstract

The topical treatment of extraocular or intraocular diseases, especially by eye drops, is the best accepted by patients. Treatment with eye drops, however, poses the issue of a poor drug bioavailability because the precorneal area, i. e., the site of drug action/absorption, is rapidly cleared of drugs by protective mechanisms of the eye, such as blinking, basal and reflex tearing, and nasolachrymal drainage. This implies the need of frequent instillations, and hence, the risk of side effects. Increasing ocular bioavailability remains a stimulating challenge for the formulators of topical systems. An approach to the task has been the reduction of drainage rate by increasing the viscosity of liquid preparations (Lee & Robinson, 1986) or resorting to mucoadhesive polymers (Hui & Robinson, 1985). The ability of a polymer to improve the ocular bioavailability of drugs by adhering to the ocular surface and binding the drug to it is a more promising property than the polymer viscosifying power (Di Colo et al., 2009), so far as fluid solutions are better tolerated than viscous ones (Winfield et al., 1990). The ocular retention of drugs administered by eye drops is also potentially improved by colloidal drug carriers, such as liposomes, submicron emulsions, nanoparticles and nanocapsules. The drugs are incorporated into these submicron particles which can be internalized into the corneal and/or conjunctival cells of the ocular epithelium (Alonso & Sanchez, 2009; Nagarwal et al., 2009). Prolonging the residence of drugs in the precorneal area serves either the extraor intraocular therapy. In those cases where a well tolerated topical treatment is desired to implement an intraocular therapy, the ocular formulation can be made to contain an effective, biocompatible, non-irritant polymeric corneal permeability enhancer. A description of the structures of the eye that come into contact with topical drug delivery systems has been reported recently (Ludwig, 2005). A summary is given in the next section, followed by an outline of the routes of intraocular drug penetration. Polysaccharides such as chitosan, xyloglucan, arabinogalactan, cellulose derivatives (methylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose), hyaluronic acid, alginic acid, gellan gum, have been studied extensively as excipients for ocular formulations. In the present survey of the literature the relevant properties of polysaccharides will be presented and discussed, with emphasis on the functions of polymers in the ophthalmic formulations where they have been used. Only polysaccharides the ocular tolerability of which has been ascertained will be dealt with.