There are few studies in the literature that deal with the effect of excipients on the kinetics of vapor phase induced hydrate-anhydrate phase transformations. The main purpose of this study was to probe the phase stability of hydrate-anhydrate systems in the presence of hygroscopic and nonhygroscopic excipients following exposure to either dehydrating or hydrating conditions. Physical mixtures and compacts of model hydrate formers (theophylline and carbamazepine) and excipients (mannitol, microcrystalline cellulose (MCC), polyvinylpyrrolidone (PVP) K12 and K90) were stored at 22 degrees C and varying relative humidities. Raman spectroscopy was used to monitor the kinetics of transformation between hydrate and anhydrate. In general, excipients were found either to have no effect or to promote dehydration. For hydrate formation, excipients could accelerate, retard, or have no influence on hydration kinetics. MCC was found to have only minimal effects on either the dehydration or hydration kinetics of model compounds, whereas mannitol enhanced dehydration but had little effect on hydration. Different PVP grades showed a variety effects: PVPK12 greatly enhanced the dehydration of both theophylline monohydrate (MT) and carbamazepine dihydrate (DC). PVPK90 also enhanced the dehydration of DC, but had a negligible effect on MT. For hydrate formation, PVPK12 was found to have a retarding effect on theophylline anhydrous (AT) transformation, but enhanced the conversion of carbamazepine anhydrous (AC) to DC, PVPK90 also retarded the hydration of AT, but had no effect on AC. Optical microscopy and X-ray powder diffraction studies suggested that PVP (in particular K12), when stored at high RH, was able to result in the partial dissolution of the active pharmaceutical ingredient and hence changed the hydration process from a solid state to a solution-mediated transformation. In summary, the effect of excipients on the kinetics of dehydration and hydration is complex and needs be rationalized in terms of several excipient properties including physical state, chemical composition, and the possibility of specific API-excipient interactions. It is concluded that a multitude of factors will dictate, and often complicate, the final effect of excipients on the phase transformation kinetics of hydrate formers.