Research

Characterisation of non-crystalline pharmaceuticals (ionic liquids/liquid crystals) by NMR spectroscopy and predictive modelling.

The aim of my PhD project is to develop methodology for the characterisation of non-crystalline pharmaceuticals (ionic liquids/liquid crystals) in order to understand the relationship between structure and properties. These relationships ultimately impact the therapeutic efficiency of the pharmaceutical. Currently, the pharmaceutical industry predominantly relies on solid active pharmaceutical ingredients (APIs), which exist in various forms. However, significant problems of solid-state drugs include polymorphism, poor solubility and a variety of other factors. The use of non-crystalline pharmaceuticals (ionic liquids/liquid crystals) can overcome many of the problems associated with solid APIs. Liquid formulations will not exhibit crystallisation or polymorphism. Furthermore, the ‘liquefaction’ of therapeutics may improve solubility, and enable novel methods of delivery. My research aims to develop methodology for the characterisation of these materials at the molecular level, and therefore provide a link between the structure and the bulk properties of such systems.

 

Figure 1. Strategies to improve the properties of pharmaceuticals.

 

The molecular structure may have an impact on drug performance, such as physical stability, solubility and absorption. In ionic liquids, interactions between APIs and counter-ions and the arrangement of molecules into supramolecular structures are key features. Nuclear Magnetic Resonance (NMR) spectroscopy is an ideal analytical technique for studying these systems. Both solution- and solid-state NMR spectroscopy are of interest to the project to characterize ionic liquids both as neat formulations and as aqueous solutions.The NMR chemical shifts and spatial information from Nuclear Overhauser Effect (NOE) data will be used to probe the types of interactions between APIs and counter ions or carriers (e.g. hydrogen bonds and aromatic ring contacts). Furthermore, diffusion information from Diffusion Ordered Spectroscopy (DOSY) and relaxation measurements will provide information on mobility, shape and size of liquid crystal systems. These NMR techniques will be developed in combination with computational simulations that are based on density functional theory (DFT), to provide an understanding of the molecular structure and dynamics of these systems.

Funding:

Chancellor's International Scholarship

GlaxoSmithKline

Sarah K. Mann

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