Crystalline Polymorphism and Molecular Structure of Sodium Pravastatin

12 pages, 14 figures, 2 tables.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.We are thankful to Ercros-Fyse s.a. for supplying products and for financial support, to Professor Jesús Sanz for the NMR spectra collection, to Professor Enrique Gutierrez-Puebla for the variable-temperature XRD collection, and to Professor Daniel Martín-Ramos for his fruitful discussions and the availability of the Xpowder package. We acknowledge the financial support of the Spanish CSIC (A.M.- I.), the Spanish MCYT, and the FEDER fund of the European Union (Grants PPQ2001-2932 and CTQ2004-04648).Peer reviewe