The object of this investigation was to perform detailed solid-state characterization studies on the different solid forms of AG337 and to determine the conditions of their interconversions. Solid-state characterization was done using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), hot stage microscopy, Karl Fischer titrimetry, ambient and variable temperature X-ray powder diffractometry (XRD) and TGA coupled with FTIR (TGA/FTIR). In addition to five polymorphic forms of the anhydrate (I(α) to I(ε)), a hemihydrate (C14H12N4OS · 2HCl · 0.5H2O, II), a monohydrate (C14H12N4OS · 2HCl · H2O; III), as well as a dihydrate (C14H12N4OS · 2HCl · 2H2O; IV) were identified. The 'as is' anhydrate, Iα, resisted water uptake until stored at 98% RH (room temperature), where it transformed directly to IV. II and III transformed to IV at RH values ≥ 7.6 and 84% respectively. Heating II and III to 130°C in the variable temperature XRD resulted in the formation of I(β) and I(γ) respectively. On the other hand, I(σ) and I(ε) were obtained when II and III were respectively stored at 60°C under vacuum. Variable temperature XRD, by providing information about the solid-state as a function of temperature, assisted in the interpretation of the DSC and TGA results. TGA/FTIR provided direct evidence that the thermal events observed in the temperature ranges of 25-150°C and 200-250°C were due to loss of water and loss of hydrogen chloride respectively. In addition to the conventional analytical techniques such as XRD, DSC, TGA and KFT, two other techniques, (variable temperature XRD and TGA/FTIR), were very useful in these solid-state characterization studies.
Copyright 2007 Elsevier B.V., All rights reserved.
- Phase transition
- Variable temperature X-ray powder diffractometry, Hydrate, AG337