Drug-Excipient Compatibility Studies. Search of interaction indicators

Abstract

This paper is the first one of a research project aimed to find and optimize methods by which drug-excipient compatibility can be reliably and quickly assessed.

A number of experimental techniques (simultaneous TG-DSC, FT-IR spectroscopy, X-ray powder diffraction, scanning electron microscopy) have been used to investigate the compatibility between a novel tricyclic β-lactam antibiotic developed by GlaxoWellcome (now GlaxoSmithKline), GV118819x, and some commonly used excipients (poly(vinylpyrrolidone), magnesium stearate and α-lactose). Binary mixtures of two different compositions have been analyzed: drug:excipient=80:20 and 20:80 (mass/mass). Both qualitative and quantitative interaction indicators have been identified. It is shown that simultaneous thermal analysis is the best suited technique in the search of interaction indicators. With a proper selection of experimental conditions it is able to reveal the thermal changes brought about by the early stages of interaction, i.e. those occurring during the measurement on physical mixtures not previously annealed under stress conditions. Such an ability is discussed, in particular, with respect to the role of the water vapour, which has been found to be a critical parameter for all our systems.