Understanding the origins of conformational disorder in the crystalline polymorphs of irbesartan

Sean P. Delaney, Duohai Pan, Michael Galella, Shawn X. Yin, Timothy Michael Korter

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

The characterization of crystalline polymorphs of drug molecules is an area of great interest since these variations in solid-state structure directly influence the physical properties of such substances. Terahertz spectroscopy provides a powerful analytical tool for these investigations and has been used here to study tautomeric polymorphism and conformational disorder in crystallized irbesartan, an antihypertensive medication. The low-frequency (<90 cm -1) terahertz spectra of both irbesartan Form A and Form B were measured and interpreted using solid-state density functional theory. The spectra reveal distinct identifying features for each polymorph and are indicative of the variations in the packing arrangements of the solids. The computational analyses of the solid-state forms also provide new insights into the origins and temperature dependence of the conformational disorder found in Form B. The results indicate that the disorder present in this crystal structure arises from a competition between internal conformational strain and external cohesive binding.

Original languageEnglish (US)
Pages (from-to)5017-5024
Number of pages8
JournalCrystal Growth and Design
Volume12
Issue number10
DOIs
StatePublished - Oct 3 2012

Fingerprint

irbesartan
Crystallization
Polymorphism
disorders
Crystalline materials
solid state
polymorphism
Terahertz spectroscopy
drugs
physical properties
Antihypertensive Agents
density functional theory
low frequencies
Density functional theory
temperature dependence
crystal structure
Physical properties
Crystal structure
spectroscopy
Molecules

ASJC Scopus subject areas

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

Cite this

Understanding the origins of conformational disorder in the crystalline polymorphs of irbesartan. / Delaney, Sean P.; Pan, Duohai; Galella, Michael; Yin, Shawn X.; Korter, Timothy Michael.

In: Crystal Growth and Design, Vol. 12, No. 10, 03.10.2012, p. 5017-5024.

Research output: Contribution to journalArticle

Delaney, Sean P. ; Pan, Duohai ; Galella, Michael ; Yin, Shawn X. ; Korter, Timothy Michael. / Understanding the origins of conformational disorder in the crystalline polymorphs of irbesartan. In: Crystal Growth and Design. 2012 ; Vol. 12, No. 10. pp. 5017-5024.
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