However, despite evidence in support of the water replacement theory, some experimental findings are contradictory to the theory. It was found that the correlation between protein stability and the preservation of secondary structure is not valid in all circumstances. On the one hand, several studies have reported significant improvements to protein stability while no spectroscopic changes of secondary structure were observed. On the other hand, there are cases where higher protein stability was achieved but with a large perturbation of the protein secondary structure. 100 For example, Costantino et al. demonstrated stability enhancement of recombinant human albumin with the presence of dextran as a stabilizer even though a lower degree of retention of secondary structure was observed compared to the formulations without additives. These findings suggest that water replacement theory is not the exclusive mechanism for the stabilization of solid proteins. In other words, thermodynamic consideration is necessary but may not be sufficient for the explanation of protein stability in the dry state. In this regard, a hypothesis that is related to the dynamics of formulations provides an alternative to uncover the stabilizing effect of sugars or polyols on dry proteins and will be discussed in the following section.