Dehydration mechanism of caffeine hydrate and structural description of driven metastable anhydrates analyzed by micro Raman spectroscopy.

This study shows the contribution of Raman spectroscopy to carefully describe the mechanism of solid-state transformation at the molecular level, by simultaneously monitoring the molecular reorganization and the water escape during the dehydration kinetics. Dehydration of monohydrate caffeine was analyzed at various temperatures. In-situ low- and high-frequency Raman investigations provide information on the long-range and local arrangement of caffeine molecules, during the dehydration kinetics and in the anhydrate state. The nature of the anhydrate was determined, from the analysis in the low-frequency region, as metastable and transient between both polymorphic forms of anhydrous caffeine. It was shown that changing the temperature mainly induces structural reorganization of caffeine molecules in the hydrate state, leading to an anhydrate more or less transformed in form I of anhydrous caffeine.