Evaluating the roles of conformational strain and cohesive binding in crystalline polymorphs of aripiprazole

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

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The relative stabilities of crystalline polymorphs are an important aspect of the manufacturing and effective utilization of pharmaceuticals. These stabilities are driven by both molecular conformational energy within the solid-state components and cohesive binding energy of the crystalline arrangement. The combined approach of experimental vibrational terahertz spectroscopy with solid-state density functional theory provides a powerful tool to study such properties and is applied here in the analysis of conformational polymorphism in crystalline aripiprazole. The low-frequency (<95 cm -1) terahertz vibrations of several aripiprazole polymorphs were measured, revealing distinct spectral features that uniquely identify each form. Solid-state density functional theory was employed to interpret the experimental terahertz spectra, correlating the observed spectral features to specific atomic motions within the crystalline lattice. The computational analysis provides insight into the formation and stability of the polymorphs by revealing the balance between the external binding forces and internal molecular forces that is ultimately responsible for the physical characteristics of the numerous crystalline polymorphs of aripiprazole.

Original languageEnglish (US)
Pages (from-to)2943-2952
Number of pages10
JournalCrystal Growth and Design
Volume13
Issue number7
DOIs
StatePublished - Jul 3 2013

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Crystallization
Polymorphism
Crystalline materials
solid state
Density functional theory
Terahertz spectroscopy
density functional theory
Vibrational spectroscopy
polymorphism
Binding energy
Crystal lattices
manufacturing
binding energy
low frequencies
vibration
Drug products
Pharmaceutical Preparations
spectroscopy
Aripiprazole
energy

ASJC Scopus subject areas

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

Cite this

Evaluating the roles of conformational strain and cohesive binding in crystalline polymorphs of aripiprazole. / Delaney, Sean P.; Pan, Duohai; Yin, Shawn X.; Smith, Tiffany M.; Korter, Timothy Michael.

In: Crystal Growth and Design, Vol. 13, No. 7, 03.07.2013, p. 2943-2952.

Research output: Contribution to journalArticle

Delaney, Sean P. ; Pan, Duohai ; Yin, Shawn X. ; Smith, Tiffany M. ; Korter, Timothy Michael. / Evaluating the roles of conformational strain and cohesive binding in crystalline polymorphs of aripiprazole. In: Crystal Growth and Design. 2013 ; Vol. 13, No. 7. pp. 2943-2952.
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