Concomitant Polymorphism in Confined Environment
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- Lee, I.S., Lee, A.Y. & Myerson, A.S. Pharm Res (2008) 25: 960. doi:10.1007/s11095-007-9424-z
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The aim of this paper is to demonstrate that multiple crystal forms can be generated on patterned self-assembled monolayers (SAMs) substrates in single experiments in a given solvent system.
Functionalized metallic islands are fabricated and utilized as individual templates for crystal formation. Taking advantage of the different wetting properties that patterned surfaces offered, arrays of small solution droplets on the nano- and pico- liter scale were produced on the substrates. Different droplet dimensions were deposited on the substrate. As the solvent evaporates from the droplets, crystals were formed within the constrained volume. Crystal habits were examined with optical microscopy while the solid form was identified with Raman microscopy.
With mefenamic acid (MA) and sulfathiazole as model pharmaceutical compounds, two and four different polymorphs, respectively, were observed under identical conditions. Moreover, it is established that the polymorphic distribution is highly dependent on the solvent evaporation rate and the solution concentration. These results imply that multiple crystal forms competitively nucleate in solution, and the probability of each form nucleating is strongly dependent on the supersaturation of the solution. Additionally, solvent was observed to play a role in controlling the solid state outcome.
Multiple crystal forms can concomitantly nucleate on patterned substrates. This technique can particularly be attractive to screen for polymorphs as elusive, metastable solid forms are favored with the creation of high supersaturation and can be stabilized due to the minimal volumes generated.