(170b) Polymorph Screening Using Self-Assembled Monolayers and Scale-up of Metastable Forms
AIChE Annual Meeting
2012
2012 AIChE Annual Meeting
Separations Division
Solid Form Selection: Cocrystals, Salts, Solvates, Polymorphs and Beyond
Monday, October 29, 2012 - 3:35pm to 3:55pm
Beginning in the 1940s with the work of Bigelow1 self-assembled monolayers (SAMs) have been used to engineer the chemistry of surfaces and have been recently applied to template the nucleation and growth of organic, inorganic and macromolecular crystals. SAMs are ordered molecular assemblies that are formed spontaneously by the adsorption of a surfactant-like molecule with a specific affinity of its headgroup to a substrate. Our group developed a patterned bifunctional SAM with hydrophilic islands surrounded by hydrophobic regions. Arrays of small hemispherical droplets can form on those hydrophilic islands when wetted with polar solutions. Each of those droplets serves as an independent crystallization experiment and thus offers a platform for high throughput polymorph screening2-5.
In this work we performed polymorph screening of a pharmaceutical active ingredient using patterned SAMs. Polymorphic forms of the crystals obtained on SAM islands were analyzed using Raman microscopy. Melting temperatures of potential novel forms were measured using hot-stage microscopy. The influence of droplet size and crystallization method (evaporation vs. anti-solvent diffusion) was also investigated. Three unreported as well as two reported forms of the compound under investigation were obtained on patterned SAM surfaces. Efforts were made to reproduce those three unreported forms in bulk using various crystallization methods with fast kinetics. At the end, we were able to make one of the three unreported forms using electrospray and further characterize it using powder xray diffraction.
[1] Bigelow, W. C.; Pickett, D. L.; Zisman, W. A., J. Coll. Sci. 1946, 1, 513-538.
[2] Lee, A. Y.; Lee, I. S.; Dettet, S. S.; Boerner, J.; Myerson, A. S., J. Am. Chem. Soc. 2005, 127, 14982-14983.
[3] Lee, A. Y.; Lee, I. S.; Myerson, A. S., Chem. Eng. Technol. 2006, 29, 281-285.
[4] Lee, I. S.; Lee, A. Y.; Myerson, A. S., Pharm. Res. 2008, 25, 960-968.
[5] Singh, A.; Lee, I. S.; Myerson, A. S., Cryst. Growth Des. 2009, 9, 1182-1185.
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