In his presentation, Eric Munson addressed the complex challenge of formulating proteins for maximum stability, particularly in the solid-state. Munson began by highlighting the inherent instability of proteins, noting that while lyophilisation (freeze-drying) can sometimes preserve protein integrity, this outcome is far from guaranteed. He emphasised that maintaining both the structure and activity of proteins is essential, especially when they are intended for non-oral delivery routes where sterility and stability are paramount.
Munson discussed the critical role of excipients, such as trehalose and sucrose, which are commonly used to stabilise proteins by preventing unwanted protein-protein interactions. He explained that the ionisation state and pH of proteins can shift during lyophilisation, potentially compromising stability. Therefore, careful control of formulation conditions is necessary to mitigate these risks.
A significant portion of the presentation focused on the use of solid-state nuclear magnetic resonance (NMR) spectroscopy as a tool for assessing protein mobility, which correlates with stability. Munson described how a relaxation time threshold of 1.5 seconds, as measured by NMR, serves as a predictor of whether a formulation will remain stable. He illustrated that while sucrose and trehalose are generally effective stabilisers, trehalose can sometimes crystallise and phase-separate from the protein, which may reduce its protective effect unless the two components are intimately mixed.
The presentation also addressed the use of mannitol as a stabiliser. Munson cautioned that, although mannitol can improve the physical appearance of lyophilised cakes, its tendency to crystallise can confine proteins in unfavourable conformations, increasing the risk of aggregation and instability.
Munson’s ongoing work involves the development of advanced NMR probes that enable non-destructive, predictive analysis of protein formulations. These technologies allow for the assessment of stability and manufacturing quality without sacrificing valuable product. By correlating NMR spectra with physical changes such as cake shrinkage and water content, Munson and his team are advancing the field’s ability to predict and optimise protein stability in pharmaceutical formulations.
