William R. D. Wood, Mihails Arhangelskis, Erika Bartůňková, Carlos E. S. Bernardes, A. Daniel Boese, Doris E. Braun, Dejan‐Krešimir Bučar, Helena Butkiewicz, Ctirad Červinka, Bartolomeo Civalleri, Nicolas Couvrat, E. De Ronde, Lorenzo Donà, Martin Dračínský, Dzmitry S. Firaha, Michal Fulem, Reynaldo Marcelino Geronia, Наталя Гончарова, Marlena Gryl, Johannes Hoja, Anna A. Hoser, Joanna Krzeszczakowska, Alexander List, Ivor Lončarić, Bruno Mladineo, Jonas Nyman, Edgar Olehovics, Mattia Raimondo, Ivo B. Rietveld, Rui Rodrigues, L. Russo, Matteo Salvalaglio, Mafalda C. Sarraguça, Jiří Šnajdr, Vojtěch Štejfa, Guangxu Sun, Paul Tinnemans, Pamela S. Whitfield, Zhuocen Yang, Y. Zhang, Sarah L. Price
High Resolution Image Download MS PowerPoint Slide We report the outcome of an interdisciplinary investigation, by the BEST-CSP network, of the kinetically favored form I and the low-temperature stable form II polymorphs of the drug sulfamerazine (SMZ). Form II can be reproducibly obtained by slurrying in acetonitrile(MeCN)/water at room temperature, though seeding with form II significantly speeds up the conversion. New structure determinations have been obtained for both forms over a wide temperature range, with both single crystal and powder X-ray diffraction methods. Room temperature FT-IR and solid-state 13 C NMR spectra are provided. The enantiotropic but practically irreversible crystal-to-crystal transition from form II to form I is observed at temperatures ranging from 150 to 170 °C in various differential scanning calorimetry (DSC) experiments, depending on sample and heating rate. The enthalpy of transition at 150 °C is measured as Δ trs H m (II → I) = 3.15 ± 0.12 kJ mol –1 . The differences in the heat capacities mean that the DSC measured enthalpies vary with the onset temperature by about 0.55 kJ mol –1 over the range of heating rates commonly used in DSC experiments. Attempts to find the solvent-mediated transition temperature were complicated by observing that slurrying experiments in both methanol and MeCN/H 2 O above 50 °C produce a new, late-identified polymorph, sulfamerazine form V, which is closely related to form I but with an alternative packing of the double layers, i.e., is a polytype polymorph. Forms I and V are only easily distinguishable by high-quality powder X-ray diffraction. Form V appears to be marginally more stable than form I across the temperature range studied. The experimental data, including heat capacities and thermal expansion rates, are used to test a wide range of assumptions and energy models for calculating free energy differences between these polymorphs, illustrating the challenges in computationally modeling the thermodynamic transition temperature between form I and II. The implications of the discovery of form V on establishing the phase diagram of sulfamerazine are discussed.