Characterizing Pharmaceutical Polymorphs Using Terahertz Spectroscopy
Date of Award
Doctor of Philosophy (PhD)
Timothy M. Korter
low-frequency vibrations, molecular binding forces, polymorphs, solid-state DFT, Terahertz spectroscopy
Physical Sciences and Mathematics
During drug manufacturing, pharmaceutical companies need to fully investigate
the solid-state assemblies of the molecules being produced. Even slight variations in the
solid-state packing arrangement of the active pharmaceutical ingredient (API) can greatly
influence the effectiveness of the product. This work investigates various aspects of the
pharmaceutical screening process, including: the characterization of polymorphs
(external changes in the solid-state packing arrangement of a solid or internal
conformational), investigation of disorder (conformational or positional), and the
formation of cocrystals. The chosen tool for these investigations is terahertz
spectroscopy. Terahertz spectroscopy probes the solid-state lattice specific, lowfrequency
vibrations (sub-100 cm-1) of molecular solids, providing a useful tool for the
differentiation of polymorphs. In this work, terahertz spectroscopy is used to detect and
identify different polymorphic materials, with up to eight polymorphs that exhibit
disorder (both internal and external), undergo solid-state phase transitions, are affected by
humidity, or exist as cocrystals. The relative stabilities of the crystalline polymorphs are
an important aspect of the manufacturing and effective utilization of pharmaceuticals and
can be investigated using solid-state density functional theory in combination with
terahertz spectroscopy. The approach of combining these experimental and theoretical
methods yields insight into the formation and stability of the polymorphs by revealing the
balance between the intermolecular and intramolecular forces that is ultimately
responsible for the physical characteristics.
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Delaney, Sean Patrick, "Characterizing Pharmaceutical Polymorphs Using Terahertz Spectroscopy" (2014). Dissertations - ALL. 86.
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