Diffusion Regimes in Binary Aqueous Solutions of Common Biopharmaceutical Stabilizers Are Differentiated by Quasielastic Neutron Scattering Spectroscopy

Diffusion properties of aqueous solutions of ubiquitous biopharmaceutical stabilizers (sucrose, sorbitol, glycerol) are studied by quasielastic neutron scattering (QENS). Molecular jump length and self-diffusion coefficients are determined for both water ( L w, D w ) and solutes (L s, D s ) in 30 wt % solute/water mixtures at 298 K. D s values scale inversely with the solute molecular size and follow Stokes–Einstein equation rank-order, while D w values, unexpectedly, show an opposite trend, with the highest D w and longest L w in the sucrose solution followed by the sorbitol and glycerol solutions. The QENS data, combined with the literature NMR reports, indicate significant heterogeneity on both nm- and μm-length scales for the water/glycerol system, while water/sucrose appears to be homogeneous on the nm-length scale. The differences in the diffusion regimes in these solutions are rationalized via thermodynamics considerations.