Due to the inevitable presence of heterosurfaces and favorable energetics, almost all crystallizations are initiated by heterogeneous nucleation. Even though the fundamental mechanistic details are lacking, heterogeneous nucleation is a highly sorted method in industrial crystallizations to control the nucleation kinetics, crystal growth, crystal size distribution, morphology and polymorphism of the desired compound. In particular, controlling polymorphism and discovery of novel polymorphic forms by applying heterosurfaces is of significant interest due to the physicochemical property variations that polymorphs can exhibit. In this study, we studied the nucleation kinetics and applied selected crystalline herosurfaces for the polymorphic control of indomethacin. To this end, we selected six organic functional crystalline substrates, L-Glutamic acid (GLU), L-Threonine (THR), Allantoin (ALT), Xanthine (XAN), Biotin (BIO) and L-Histidine (HIS) and Sodium Chloride (NaCl) as substrates. The effectiveness of each substrate in enhancing the nucleation rates of indomethacin was examined with a high throughput microscopic method and polymorphic selection towards each form of IMC was investigated with a combination of microscopy and Raman spectroscopy. Furthermore, we conducted Raman spectroscopy based crystal face indexing to identify the in contact faces for the substrate and IMC. This work aims to elucidate the role of intermolecular interactions and substrate functional groups at the substrate-solution interface in driving the nucleation kinetics and polymorphic selection in general. We expect this extension of fundamental understanding to provide the opportunity to rationally affect the nucleation stage with the aid of intentionally added well-defined crystalline heterosurfaces and to improve the control over the desired crystal properties.<br/>

Application of crystalline substrates for nucleation control and polymorphic selection of Indomethacin

256th National Meeting (2018)

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