Polymorphism of Nifedipine: Crystal Structure and Reversible Transition of the Metastable β Polymorph

We report the first structural determination of the metastable β polymorph of nifedipine (NIF) by single-crystal X-ray diffraction. Stable, high-quality crystals were grown from the melt in the presence of a polymer dopant. Our β NIF structure is characterized by a unit cell similar to that of the structure recently proposed from powder diffraction, but significantly different molecular conformations. Unlike the stable α polymorph, β NIF undergoes a reversible solid-state transformation near 60 °C. The now available β NIF structure clarifies some confusion concerning NIF polymorphs and enables inquiries into the structural basis for the selective crystallization of β NIF from glasses. We report that another polymorph crystallizes concomitantly with β NIF from the supercooled melt and transforms to β NIF at room temperature; this polymorph also undergoes reversible solid-state transformation