PRESERVATIVE EFFICACY TESTS IN FORMULATED NASAL PRODUCTS - REPRODUCIBILITY AND FACTORS AFFECTING PRESERVATIVE ACTIVITY

Preservative efficacy tests were performed in triplicate on each of th ree batches of three formulated nasal spray preparations to assess the inter- and intra-batch variation in preservative performance which ty pically results from these procedures, and to assess the relative impo rtance of factors influencing preservative performance in nasal produc ts. Tests were conducted using procedures conforming, as far as possib le, to both the European and the US pharmacopoeias and the results int erpreted using the performance criteria of both. Despite the adoption of practices designed to maximize reproducibility, a marked variation in the degree of microbial inactivation was observed, both within and between batches of product. A preservative system comprising benzalkon ium chloride and phenylethyl alcohol was found to be far superior to c ombinations of either benzalkonium chloride plus disodium edetate or p otassium sorbate plus disodium edetate, both of which failed to satisf y the EP performance criteria on a number of occasions. Proposals are made for the adoption of inactivation criteria which incorporate reali stic error limits reflecting the inherent problems of reproducibility of the viable counting procedures involved.