Javier Ellena - Solvothermal Preparation of Drug Crystals: Didanosine

Version 1

      Publication Details (including relevant citation   information):

        Martins, Felipe T., Legendre, Alexandre O., Honorato, Sara   B., Ayala, Alejandro P., Doriguetto, Antonio C., Ellena, Javier.   CRYSTAL GROWTH & DESIGN    Volume:   10    Issue: 4    Pages:   1885-1891    Published: APR 2010

      Abstract:

      Abstract: For the first time, crystals of suitable size for X-ray   diffractometry structure determination (Dian important anti-HI V   drug were prepared under solvothermal conditions. In this study,   the crystal structure of didanosine (2',3'-dideoxyinosine, ddI)   in the form of a hydrate was determined using single-crystal   X-ray diffractometry. Powder X-ray diffraction analysis revealed   that the solid-state phase of the drug incorporated into   pharmaceutical solid dosage forms is isostructural to the   solvothermally prepared ddI material, even though they do not   exhibit an identical chemical composition due to different water   fractions occupying hydrophobic channels formed within the   crystal lattice. Two ddI conformers are present in the structure,   in agreement with a previous structure elucidation attempt.   Concerning the keto enol equilibrium of ddI, our crystal data and   vibrational characterizations by Fourier transform infrared   (FTIR) and FT-Raman spectroscopy techniques were conclusive to   state that both conformers exist in the keto form, contrary to   solid-state NMR spectroscopic assignments that suggested ddI   molecules occur as enol tautomers. In addition, characterizations   by thermal (differential scanning calorimetry) and spectroscopic   techniques allowed us to understand the structural similarities   and the differences related to the hydration pattern of the   nonstoichiometric hydrates.

      Co-Authors:
      javiere@ifsc.usp

      Address (URL): http://pubs.acs.org/doi/abs/10.1021/cg9015959