Fluidisation is a common unit operation in the pharmaceutical industry. The unique nature of heat and mass transfer during fluidisation creates a risk for solid-state changes. Such changes are important because they can affect therapeutic and manufacturing behaviour of pharmaceutical materials and products. There are no generally accepted solutions for direct monitoring of solid-state properties during fluidisation. In this paper, in-line near-infrared and Raman spectroscopy were used to directly monitor, at the molecular level, the solid-state form of a model substance. Theophylline monohydrate granules were fluidised at 328 and 333 K and absolute humidity and pressure measurements indicated that dehydration had occurred. Using spectroscopy, conversion from the monohydrate to the anhydrate form was directly determined and monitored in real time. Near-infrared and Raman spectroscopy were complementary, since the former is particularly sensitive to water and the latter to crystal structure changes. Furthermore, the conversion was tracked quantitatively with both spectroscopic methods using the multivariate analysis method, partial least squares regression. Conversion to theophylline anhydrate was confirmed by X-ray powder diffraction and water content analysis post-fluidisation. This study shows that near-infrared and Raman spectroscopy are viable in-line methods to observe and quantify solid-state changes in real time. (c) 2006 Elsevier Ltd. All rights reserved.