Polymorphs and a Hydrate of Furosemide–Nicotinamide 1:1 Cocrystal

Five anhydrous polymorphs (forms I–V) and one
hydrate of
furosemide–nicotinamide 1:1 cocrystal were discovered, and
their solid-state properties were characterized using X-ray powder
diffraction and differential scanning calorimetry. The crystal structures
of forms I–IV were determined from the X-ray powder diffraction
data and showed the structural differences between forms, which are
mainly attributable to molecular conformations and supramolecular
synthons. The slurry conversion experiments revealed that the order
of thermodynamic stability of the polymorphs at 25 °C is I >
III > II > V > IV. Dynamic vapor sorption analysis and X-ray
single-crystal
structure determination of the hydrate were conducted to study the
dehydration mechanism. We observed structural similarities between
the hydrate and its dehydrate, form IV, such as lattice parameters
(except the a-axis length), synthons between furosemide
and nicotinamide molecules, and the molecular conformation of furosemide;
after dehydration, however, the a-axis contracted
and nicotinamide molecules were displaced, along with the pyridine
ring twisting.