This study reports global and local monoclonal antibody (mAb)–excipient interactions and the resulting thermodynamic and stabilization effects.
Molecular dynamics simulations are applied to quantify the interactions of key excipients (sucrose, sorbitol, arginine, citrate, histidine and NaCl) used in the formulations of three mAbs. The dynamic surface properties of the mAbs and preferential interaction coefficients for the excipients based on validated potential parameters are computed, in addition to the spatial aggregation propensity.
A high molar concentration of citrate induces a large degree of structural distortion in the mAb structure. The total quantities of sucrose, arginine and Cl that interact with the three mAbs are different, implying that each excipient exerts a different stabilizing effect on each mAb. The equilibrated populations of the excipient and water near the local mAb domains vary, with each mAb exhibiting a unique pattern. The local domain's surface properties rather than the properties of the individual residues primarily control the specific preferential interactions. For sucrose, preferential binding to mAbs correlates to a large extent with the relative degree of hydrogen bonding.
These results enrich our understanding of the molecular bases for the varied interaction behaviours of individual excipients.