​Amorphous solid (glassy) states are ubiquitous in both nature and industrial pharmaceutical products. For example, protein molecules are usually embedded in a freeze-dried amorphous sugar matrix to improve stability and shelf life.

The ability of molecules to move within the structure, or ‘molecular mobility’, has been traditionally thought of as the key property to consider when explaining the physical and chemical stability of diverse pharmaceutical systems. Although increased research efforts have begun to build up a comprehensive picture of the molecular mobility landscape, the relationship between molecular mobility and critical properties of amorphous pharmaceuticals are not straightforward.

The properties investigated in this study were the incomplete freezing leading to the existence of unfrozen water in aqueous solutions at sub-zero temperatures and the role of water in the chemical stability of amorphous pharmaceuticals. Using wide angle neutron scattering, the researchers observed nano-sized water clusters in aqueous pharmaceutical glasses and proposed that these clusters influenced both of the properties studied.

They demonstrated that the inhibition of freezing can be a direct consequence of the confinement of these water clusters in a solidified matrix of an amorphous solute. Considering the importance of proton transfer in many chemical processes, they suggest that the water cluster formation could catalyse proton transfer, promoting chemical instability.