Low-temperature phase transition in crystalline aripiprazole leads to an eighth polymorph

Sean P. Delaney, Tiffany M. Smith, Duohai Pan, Shawn X. Yin, Timothy M. Korter

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

A new crystalline polymorph (Form VIII) of the antidepressant drug aripiprazole has been discovered, resulting from a previously unknown enantiotropic phase transition from Form II at 225 K. This finding makes aripiprazole one of the most polymorphic flexible organic solids currently known, equaling flufenamic acid in number of solved forms (eight polymorphs). Enantiotropic solid-solid phase transitions are relatively uncommon for pharmaceuticals; however, for the aripiprazole system, such phase transitions play a central role in several of its polymorphic transformations. A combination of solid-state density functional theory and single-crystal X-ray diffraction has been used to investigate the energies involved in the formation of Form VIII. This work reveals that Form VIII is stable despite containing molecules with unfavorable conformations. The stability of this polymorph originates from improved intermolecular binding energy due to enhanced London dispersion forces at low temperatures.

Original languageEnglish (US)
Pages (from-to)5004-5010
Number of pages7
JournalCrystal Growth and Design
Volume14
Issue number10
DOIs
StatePublished - Oct 1 2014

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics

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