Solvothermal Preparation of Drug Crystals: Didanosine

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.

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Brazilian Research Council CNPq[477201/2009-1]

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Brazilian Research Council CNPq[302441/2009-3]

FAPESP (Fundacao de Amparo Pesquisa do Estado de Sao Paulo)[2007/07185-5]

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

FAPESP (Fundacao de Amparo Pesquisa do Estado de Sao Paulo)[2009/14705-0]

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

FAPEMIG (Fundacao de Amparo a Pesquisa do Estado de Minas Gerais)[APQ-2011-5.02/07]

Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)

FAPEMIG (Fundacao de Amparo a Pesquisa do Estado de Minas Gerais)[APQ-6010-5.02/07]

Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)

Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)

FAPEMIG (Fundacao de Amparo a Pesquisa do Estado de Minas Gerais)[APQ-02685-09]

CAPES (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior)[PNPD2008]

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

FUNCAP (Fundacao Cearense de Amparo ao Desenvolvimento Cientifico e Tecnologico)

Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico (FUNCAP)

IPDI (Instituto de Pesquisa, Desenvolvimento e Inovacao)

IPDI (Instituto de Pesquisa, Desenvolvimento e Inovacao)