Insights into phase stability of anhydrous/hydrate systems: a Raman‐based methodology

Abstract

AbstractFT‐Raman spectroscopy turns out to be a powerful technique to evaluate the amount of polymorphic and pseudopolymorphic forms in crystalline samples—which is particularly relevant in pharmaceutical sciences. This paper presents a methodology that allows successful quantitative evaluation of the solid‐state hydration and dehydration processes, using FT‐Raman spectroscopy. All the steps required for a reliable evaluation of the hydration/dehydration process are illustrated for the caffeine system, a particularly challenging system presenting limited spectral differences between the pseudopolymorphs. The hydration process of caffeine was found to occur in a single‐step process with a half‐life time of ca 13 h, while the dehydration occurs through a two‐step mechanism. The critical relative humidity was found to be at ca 81 and 42% for anhydrous and hydrate caffeine forms, respectively. Copyright © 2009 John Wiley & Sons, Ltd.