FORMULATION AND EVALUATION OF TIMOLOL MALEATE OPHTHALMIC SOLUTION USING VARIOUS PRESERVATIVES

Abstract

Preservatives provide important and necessary antimicrobial activity and plays very important role in maintaining the sterility and shelf-life of multi-dose formulations of topical ophthalmic medications. Any drop delivered in a multi-dose format must have some mechanism for maintaining the sterility of the contents throughout its intended length of use. In topical preparations, antimicrobial activity is most often achieved through the addition of preservatives. The most commonly used preservative in topical drops of any form is benzalkonium chloride (BAK). Whilst it is known to be an effective antimicrobial agent, demonstrating efficacy against a wide variety of common pathogens, considerable evidence, often from its use in glaucoma medications, also exists detailing the deleterious effects it has on the ocular surface, particularly when used over an extended period of time. It can be argued that the undesirable effects of BAK have contributed to a movement into preservative-free topical preparations. BAK is quaternary ammonium compound and this compound has been shown to cause tear film instability, loss of goblet cells, conjunctival squamous metaplasia and apoptosis, disruption of the corneal epithelium barrier, and damage to deeper ocular tissues. The intend of the present study was to formulate a formulation for Timolol Maleate (0.5%) ophthalmic solution using different concentration of different preservatives to know other alternatives of Benzalkonium Chloride and which is less harmful than Benzalkonium Chloride. While selecting the type and concentration of preservatives, it was considered that added quantity of preservative must meet compendial requirement of Preservative Efficacy Testing. Various preservatives like Benzalkonium chloride, Phenyl Mercuric Nitrate, Chlorbutol and Stabilised Oxychlorocomplex were used. All the formulations were evaluated and checked for effective antimicrobial activity without interference with the mechanism of action of the active ingredient.