Crystalline Polymorphism and Molecular Structure of Sodium Pravastatin

In this work different crystallization processes of sodium pravastatin are explored and a new polymorph is
obtained. The analytical results of powder X-ray diffraction (PXRD) and thermal analysis for this new
polymorph indicate that it is different from the polymorphs previously reported. This new crystal form shows
different physical−chemical properties than the previous forms, such as crystallographic structure, thermal
behavior, and melting point, 181.5 °C. Besides, all crystallization processes previously reported use an aprotic
solvent as antisolvent. However, we propose a new crystallization process for sodium pravastatin that uses
only protic solvents, overcoming industrial scaling and environmental problems. Variable-temperature PXRD
experiments show a transformation between different crystal forms in the range of 80−120 °C. Solid-state
13C NMR, reported in this work for the first time, and Fourier transform infrared (FT-IR) studies of some
polymorphs show some differences in intermolecular interactions, especially with carboxylate and hydroxyl
groups. Quantum mechanical calculations of the pravastatin molecule are also presented for the first time,
obtaining a molecular structure similar to the experimental structure existing within the crystal lattice of the
tert-octylamonium salt of pravastatin.