Investigation of Structure-Electromechanical Properties of Pharmaceutical Crystals: Implications to Bulk Processing

Das, Kaustav (2025) Investigation of Structure-Electromechanical Properties of Pharmaceutical Crystals: Implications to Bulk Processing. PhD thesis, Indian Institute of Science Education and Research Kolkata.

Text (PhD thesis of Kaustav Das (20RS062)) 20RS062.pdf - Submitted Version Restricted to Repository staff only Download (12MB)

Abstract

Surface chemistry plays a crucial role in controlling physiochemical properties of molecular crystals. In case of pharmaceutical crystals, one of the common surface phenomena is generation of surface charges during processing which is normally attributed to triboelectricity. Apart from this, there may exist other sources of surface charges in pharmaceutical crystals. For example, noncentrosymmetric molecular crystals under uniform mechanical stress produce surface charges, termed as piezoelectricity. Some of our recent findings intrigued us to investigate the formation of surface charges by mechanical fracture in the vast domain of pharmaceutical crystals. In my doctoral research, I have investigated emergence of mechanical fracture induced surface charges in more than twenty pharmaceutical crystals. I have shown that centrosymmetric (CS) crystals do not show surface charges upon mechanical fracture, however noncentrosymmetric (NCS) crystals may show the same. Specifically, noncentrosymmetric polar (NCS-P) crystals with non-trivial unit cell dipole moment have tendency to show surface charge generation, however the crystal structure and intermolecular interactions play a critical role. These novel findings on electromechanical properties of crystals are further correlated with their underlying crystal structure, symmetry, piezoelectric coefficient, macro- and nano-mechanical properties. Detailed Kelvin Probe Force Microscopy (KPFM) experiments are performed to establish the nature of polarity (positive or negative) of surface charges in the complimentary faces. Also, the longevity of surface charges is investigated by considering time, humidity and solvent-dependent conditions are variables. Further, flowability, compactibility and tabletability studies are performed to establish the effect of surface charges on the physicochemical properties of bulk powders. This study provides an overview of the novel electromechanical coupling phenomena in a variety of pharmaceutical crystals, paving the way for predicting likelihood of the surface charge generation in molecular materials, such as agrochemicals, fine chemicals and nutraceuticals. Further, I have explored autonomous self-healing in a multiferroic pharmaceutical crystal, which stands as a unique example of an API with multifunctionalities. It is noteworthy that the inherent biocompatible and biodegradable nature of API crystals with various supramolecular interactions formed by different functional groups in structure, make them suitable candidates in many applications. Finally, I have attempted to provide design strategy for autonomous self-healing in related peptide-based crystals which can be further used for fabricating self-repairable bio-compatible electromechanical devices.

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