Perfusion calorimetry in the characterization of solvates forming isomorphic desolvates.

In this study, the potential of perfusion calorimetry in the characterization of solvates forming isomorphic desolvates was investigated. Perfusion calorimetry was used to expose different hydrates forming isomorphic desolvates (emodepside hydrates II-IV, erythromycin A dihydrate and spirapril hydrochloride monohydrate) to stepwise increasing relative vapour pressures (RVP) of water and methanol, respectively, while measuring thermal activity. Furthermore, the suitability of perfusion calorimetry to distinguish the transformation of a desolvate into an isomorphic solvate from the adsorption of solvent molecules to crystal surfaces as well as from solvate formation that is accompanied by structural rearrangement was investigated. Changes in the samples were confirmed using FT-Raman and FT-IR spectroscopy. Perfusion calorimetry indicates the transformation of a desolvate into an isomorphic solvate by a substantial exothermic, peak-shaped heat flow curve at low RVP which reflects the rapid incorporation of solvent molecules by the desolvate to fill the structural voids in the lattice. In contrast, adsorption of solvent molecules to crystal surfaces is associated with distinctly smaller heat changes whereas solvate formation accompanied by structural changes is characterized by an elongated heat flow. Hence, perfusion calorimetry is a valuable tool in the characterization of solvates forming isomorphic desolvates which represents a new field of application for the method.

The study of different solid forms of Emodepside.

Emodepside is an endoparasiticide used in veterinary drugs. It exists in four different crystal forms which were characterised using DSC, TGA, evolved gas analysis (using FT-IR spectroscopy), hot-stage microscopy, FT-Raman, FT-IR and FT-NIR spectroscopy and powder X-ray diffraction. Thermal analysis showed that the forms II-IV contain considerable amounts of water being easily lost upon heating. Hot-stage microscopy indicated that the crystal structures do not change upon the loss of water. To examine whether the forms II-IV are hydrates or modifications of Emodepside having water adsorbed to the crystal surface and/or absorbed into disordered defect regions, the behaviour of the forms at different relative humidities was analysed using FT-Raman and FT-NIR spectroscopy and vapour sorption analysis. Changes in the C=O stretching region in the Raman spectra upon the removal of water revealed that all three forms represent non-stoichiometric hydrates forming isomorphic dehydrates. Sorption analysis indicated the presence of localised water molecules in the structure of form IV. Several OH combination bands of water were found in the NIR spectrum of each form indicating differently bound water molecules. Crystal structure analysis of form IV at ambient humidity revealed four well-defined water positions in the asymmetric unit.