Can Solid-State NMR Help Shed Light on Pharmaceutical Solid-State Stability?

This project in collaboration with Pfizer will assess how the stability of various Active Pharmaceutical Ingredients (APIs) in novel therapies and how they may interact with their excipients using solid-state nuclear magnetic resonance. The technique will be used to improve the understanding of product instability. This will allow the shelf life of potential therapies to be determined as well as earlier final formulation selection, based on the improved understanding of the causes of instability. This will be achieved by using a range of solid-state NMR techniques. Multinuclear techniques including 1H, 13C, 19F and 31P will be used to explore the chemical and physical environment of the active ingredient in solid state formulation matrices. Further, the effects of varying the manufacturing process upon the active: non-active ingredient interface will be explored and correlated with product stability.

The overall project aim is to apply a wide range of multinuclear NMR approaches that will provide an evaluation of NMR to understanding the factors that can affect chemical degradation in the solid state.

Specific objectives will include applying 13C cross polarisation (CP) magic angle spinning, for the analysis of APIs and API: excipient mixtures to determine the effects on the phys/chem environment of the API at the interface within novel therapies. Separately, 19F solid-state NMR of an API on its own and when mixed with excipients will be studied in order to assess the ability to differentiate and quantify APIs in different environments in solid samples; evaluating the relevance of NMR information to the stability of the sample.

Currently, solid-state NMR is considered to be an under-utilized technique in this field of research. The project will allow a wide range of potential solid-state NMR approaches to be evaluated leading to a better understanding of the techniques that provide the most useful information to understand solid state stability. As well as this, it will determine the types of drugs that are most amenable for study using these techniques, providing information on structure and dynamics. Further, polymorphs can be determined in pure drugs and formulated tablets in which excipients are present.

This Project aligns with ESPRC's Healthcare Technologies theme and 'Developing Future Therapies' area, and is centred on Analytical Science.