In the present study, the dehydration process of caffeine hydrate (CAH) was investigated by calibrating the moisture content in the caffeine tablet using backscattering Raman spectroscopy (BRS) and transmission Raman spectroscopy (TRS). The detectable depth of BRS is limited by its shallow laser penetration, while TRS is a powerful tool to determine the content of active pharmaceutical ingredients in a tablet. Our results suggest that the accuracy of a TRS-based calibration model falls beyond that of a BRS-based model. Based on the calibration used, the model was built by calculating the differences in the crystalline structures between hydrate and anhydrous caffeine. Moreover, it was demonstrated that the dehydration process occurred by switching water molecules between hydration sites of caffeine. (C) 2017 Elsevier B.V. All rights reserved.