Rapid and Sensitive Method for a Kinetic and Preformulation Study of an Investigational Antiviral Drug

Abstract

Win 51711 is an oxazoline compound investigated for antiviral activity against rhinovirus. The drug is not very soluble in water (< 1 mcg/mL) above pH 5 but is quite soluble at more acid pH's due to salt formation with the oxazoline nitrogen. Formulation of the drug depends on selective use of excipients. Acidic excipients destabilize the drug whereas neutral and basic ingredients have no adverse effect on stability. The present study reports on an HPLC method developed to separate the drug and the products under stressed conditions. The products of hydrolysis were identified and found to have little or no antiviral activity. A simple spectrophotometric method was also developed. This method was found to have an advantage of assaying solutions of Win 51711 and its hydrolysis product without separation. The HPLC method was used in selecting compatible excipients which resulted in a formulation with long term stability.