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.