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ABSTRACT: To discover, elucidate the structure-activity relationship (SAR), and explore the mechanism of action of excipients able to drastically lower the viscosities of concentrated aqueous solutions of humanized monoclonal antibodies (MAbs). Salts prepared from hydrophobic cations and anions were dissolved into humanized MAbs solutions. Viscosities of the resulting solutions were measured as a function of the nature and concentration of the salts and MAbs. Even at moderate concentrations, some of the salts prepared herein were found to reduce over 10-fold the viscosities of concentrated aqueous solutions of several MAbs at room temperature. To be potent viscosity-lowering excipients, the ionic constituents of the salts must be hydrophobic, bulky, and aliphatic. A mechanistic hypothesis explaining the observed salt effects on MAb solutions' viscosities was proposed and verified.