Surface Adsorbed Templates for Directing the Crystal Growth of Entacapone as Monitored Using Process Analytical Techniques

Crystallization of entacapone (E-2-cyano-N,N-diethyl-3-(3,4-dihydroxy-5-nitrophenyl) propenamide) in acetone solution at the 500 mL scale using a self-assembled layer of the host material on Au(111) as a seeding template was studied and monitored using attenuated total reflectance (ATR)-UV-vis spectroscopy and focused beam reflectance measurement (FBRM). The data reveal that the template promotes crystal growth at lower supersaturations and at an increased rate when compared to experiments carried out without the template. Crystals prepared using the template are also found to have superior properties compared to crystals produced without the template. Notably, use of the template produces crystals with a much narrower size distribution, greatly increased perfection and a more equant crystal morphology. These observations are consistent with the template providing a sympathetic surface for the promotion of crystallization through an analogous mechanism to that associated with conventional seeding, but with the added advantage of conferring a well-ordered, easily reproducible and more robust process.