New technology for the investigation of water vapor sorption-induced crystallographic form transformations of chemical compounds: a water vapor sorption gravimetry-dispersive Raman spectroscopy coupling.

In this study, a new dynamic water vapor sorption gravimetry (DWVSG)-Raman spectroscopy coupled system is presented and described for the investigation of water (de)sorption-induced solid-phase transition of active pharmaceutical ingredients (APIs). The innovative characteristic of the system is the possibility to measure up to 23 samples gravimetrically and spectroscopically in one sorption/desorption experiment. The used dispersive RXN1 Raman system with a 6-mm laser spot P(h) AT probe head is ideal for this kind of coupled technology, as the energy density at the point of measurement of the sample is low, which grants that gravimetrical data and the state of the sample (phase transformations or even degradation) are not influenced by the laser beam. The capabilities of the system were tested by the investigation of a crystalline, nonstoichiometric hydrate form (form 1) and the corresponding X-ray amorphous form of an API (SAR474832). For the crystalline hydrate form, it was possible to correlate the weight loss at low humidities to a crystallographic phase transition (form 2). Furthermore, it was possible to show that the phase transition is reversible upon water uptake (sorption cycle); however, a further intermediate crystal form (form 3) is involved in the rehydration process. By multivariate curve resolution analysis of the Raman spectra, the form distribution diagrams of the desorption/sorption cycle could be constructed. For the amorphous material, the recrystallization process was monitored by the changes in the Raman spectra. The recrystallization point was detected at high humidities (>90% relative humidity), the crystal phase formed was identified (form 1), and the time needed for the conversion into the crystalline state was determined. The form transformation processes were visualized by contour plots (time/humidity vs. wavenumber vs. Raman intensity). In summary, it was concluded that the presented water sorption gravimetry-Raman spectroscopy coupling is a powerful tool to study solid-state transitions of pharmaceutical compounds or galenic formulations. The information obtained can, for example, be used to optimize drying, conditioning, or rerystallization processes of chemical products or to determine their optimal storage conditions. This is especially interesting for physically and chemically labile hydrate phases.