Aqueous wet massing of stable anhydrous theophylline (A) with polyvinylpyrrolidone (PVP) resulted in its complete transformation to theophylline monohydrate (M). Drying at 458C, resulted in the formation of metastable anhydrous theophylline (A*) which then transformed to A. PVP, a known crystallization inhibitor, was effective in inhibiting the A* ! A transition. The higher molecular weight polymer, PVP K90, was more effective in inhibiting the A* ! A transition as compared to PVP K17. The disappearance of M, and the formation of A* and A was simultaneously monitored by XRD. An increase in the drying temperature from 45 to 558C accelerated the A* ! A transition. In granules prepared by the high-shear process, approximately 50% of theophylline existed as A and the rest as A*. In contrast, the fluid-bed granulation process yielded granules containing only A. Thus, the physical form of theophylline in tablets was influenced by the molecular weight of the binding agent, the granulation method, and the drying temperature. Using A as the starting material, tablets were manufactured by high-shear aqueous wet granulation process and the A* content was quantified. These tablets were stored under various relative humidity (RH) conditions at 258C for 2 weeks. Storage at RH ! 33% caused complete A* ! A conversion accompanied by a pronounced decrease in the initial dissolution rate indicating that phase transitions during processing and storage can have a significant influence on product performance.