Water Sorption Induced Transformations in Crystalline Solid Surfaces - Characterization by Atomic Force Microscopy

D. Chen,1 Greg Haugstad,2 J. Z. Li,3 and R. Suryanarayanan1

1Department of Pharmaceutics and 2Characterization Facility, University of Minnesota, Minneapolis, Minnesota 55455, and 3Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut 06877


The effect of water sorption on the mobility of molecules on the surface of a crystalline anhydrous solid was investigated to understand the mechanism of its transformation to the corresponding hydrate. Theophylline was chosen as the model compound. The transition water activity for anhydrate to hydrate transformation, RHT, and the deliquescence RH, RH0, was determined to be 62% and 99%, respectively (25 °C). Atomic force microscopy (AFM) was used to study the surface changes of theophylline above and below the transition water activity. Contact-mode AFM showed that the jump-to-contact distance increased appreciably above RHT, suggesting formation of solution on the surface. At RHT < RH < RH0, using dynamic (AC/“tapping” mode) AFM, the movements of surface steps were visualized. These results from AFM indicated that, below RH0, the formation of a thin solution film significantly increased surface mobility. Furthermore, when the anhydrate crystal surface was seeded with the hydrate, the propagation of a new hydrate phase was observed by polarized light microscopy. In conclusion, atomic force microscopy provided direct evidence that the phase transformation of anhydrous theophylline to theophylline monohydrate in the solid-state is mediated by a surface solution as a result of water adsorption.