Polymer templating of supercooled indomethacin for polymorph selection

Scott C McKellar, Andrew J Urquhart, Dimitrios A Lamprou, Alastair J Florence

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Reported here is a relatively simple technique for polymorph screening of pharmaceutical compounds that are thermally stable. Polymer libraries have previously been used as surfaces to influence, or direct, the crystalline form adopted by an active pharmaceutical ingredient on crystallization from solution. In this current work, we demonstrate the polymorph-directing effect of homopolymer surfaces in the absence of solvent by recrystallization from the supercooled melt. When the nonsteroidal anti-inflammatory drug indomethacin is melted, cooled, and subsequently reheated above its glass transition temperature on an untreated surface, it has a proclivity to crystallize as its δ polymorph. On certain polymer surfaces, however, it preferentially crystallizes as the α polymorph, as a direct result of polymer templating. The method is well-suited to implementation in multiwell plate formats requiring only small amounts of material and enabling multiple experiments to be carried out in parallel with samples readily characterized using X-ray powder diffraction.
LanguageEnglish
Pages155-159
Number of pages5
JournalACS Combinatorial Science
Volume14
Issue number3
Early online date14 Feb 2012
DOIs
Publication statusPublished - 2012

Fingerprint

Polymorphism
Indomethacin
Polymers
Pharmaceutical Preparations
Crystallization
Homopolymerization
X ray powder diffraction
Screening
Anti-Inflammatory Agents
Crystalline materials
Experiments

Keywords

  • indomethacin
  • polymorph screening
  • polymer templating
  • polymer-induced
  • heteronucleation
  • glass transition

Cite this

McKellar, Scott C ; Urquhart, Andrew J ; Lamprou, Dimitrios A ; Florence, Alastair J. / Polymer templating of supercooled indomethacin for polymorph selection. In: ACS Combinatorial Science. 2012 ; Vol. 14, No. 3. pp. 155-159.
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Polymer templating of supercooled indomethacin for polymorph selection. / McKellar, Scott C; Urquhart, Andrew J; Lamprou, Dimitrios A; Florence, Alastair J.

In: ACS Combinatorial Science, Vol. 14, No. 3, 2012, p. 155-159.

Research output: Contribution to journalArticle

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AB - Reported here is a relatively simple technique for polymorph screening of pharmaceutical compounds that are thermally stable. Polymer libraries have previously been used as surfaces to influence, or direct, the crystalline form adopted by an active pharmaceutical ingredient on crystallization from solution. In this current work, we demonstrate the polymorph-directing effect of homopolymer surfaces in the absence of solvent by recrystallization from the supercooled melt. When the nonsteroidal anti-inflammatory drug indomethacin is melted, cooled, and subsequently reheated above its glass transition temperature on an untreated surface, it has a proclivity to crystallize as its δ polymorph. On certain polymer surfaces, however, it preferentially crystallizes as the α polymorph, as a direct result of polymer templating. The method is well-suited to implementation in multiwell plate formats requiring only small amounts of material and enabling multiple experiments to be carried out in parallel with samples readily characterized using X-ray powder diffraction.

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