LC STUDIES ON THE POTENTIAL INTERACTION OF PARABEN PRESERVATIVES WITHSORBITOL AND GLYCEROL

Pharmaceutical formulations often contain one or more paraben preserva tives in conjunction with a polyol such as sorbitol or glycerol. In on e of these experimental formulations a number of unknown polar peaks h ave been detected near the solvent front by reversed-phase LC. These d egradation products were not attributable to the active drug component or a hydrolysis product. The possibility of an interaction between th e polyols and paraben preservatives has been explored using a three-va riable, two-level, factorial design to determine the relative signific ance of the factors involved in the formation of these unknown peaks. The factors examined were pH, temperature and the ratio of polyol to p araben. This study has shown that pH and temperature are key factors a ffecting the formation of these unknown peaks. On the basis of these r esults suitable conditions can be suggested for minimizing the product ion of these unknown peaks. It seems clear that a number of pharmaceut ical formulations containing a polyol and a paraben would present pote ntial problems for assay validation on storage owing to the formation of these degradation products, particularly if the drug component is p olar and elutes near the solvent front.