Polymer templating of supercooled indomethacin for polymorph selection

ACS Comb Sci. 2012 Mar 12;14(3):155-9. doi: 10.1021/co200175e. Epub 2012 Feb 24.

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.

Publication types

  • Letter

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Cold Temperature
  • Crystallization*
  • Glass / chemistry
  • Indomethacin / chemistry*
  • Molecular Structure
  • Polymers / chemistry*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Polymers
  • Indomethacin