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Concomitant polymorphism in confined environment.

In Sung Lee1, Alfred Y Lee, Allan S Myerson

  • 1Department of Chemical & Biological Engineering, Illinois Institute of Technology, Chicago, Illinois 60616, USA.

Pharmaceutical Research
|September 27, 2007
PubMed
Summary
This summary is machine-generated.

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This study shows patterned surfaces can generate multiple crystal forms in one experiment. This method aids in screening for pharmaceutical polymorphs by controlling supersaturation and solvent evaporation.

Area of Science:

  • Materials Science
  • Crystallography
  • Pharmaceutical Science

Background:

  • Controlling crystal polymorphism is crucial for drug development.
  • Existing methods for polymorph screening can be time-consuming and may miss metastable forms.

Purpose of the Study:

  • To demonstrate the generation of multiple crystal forms on patterned self-assembled monolayers (SAMs) substrates within a single experiment.
  • To establish a novel method for polymorph screening using micro-scale solution droplets.

Main Methods:

  • Fabrication of functionalized metallic islands as templates for crystal formation.
  • Generation of nano- and pico-liter scale solution droplets with varying dimensions on patterned substrates.
  • Analysis of crystal habits using optical microscopy and solid form identification with Raman microscopy.

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Main Results:

  • Successfully generated two and four different polymorphs for mefenamic acid and sulfathiazole, respectively, under identical conditions.
  • Demonstrated that polymorphic distribution is highly dependent on solvent evaporation rate and solution concentration.
  • Confirmed that multiple crystal forms competitively nucleate, influenced by supersaturation and solvent effects.

Conclusions:

  • Patterned substrates enable the concomitant nucleation of multiple crystal forms.
  • This technique is advantageous for polymorph screening, favoring elusive metastable forms through controlled supersaturation and minimal volumes.