Structure-activity relationship for hydrophobic salts as viscosity-lowering excipients for concentrated solutions of monoclonal antibodies.
OBJECTIVE
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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Zheng
Z
Guo
Alvin
A
Chen
Roger A
RA
Nassar
Bernhard
B
Helk
Claudia
C
Mueller
Yu
Y
Tang
Kapil
K
Gupta
Alexander M
AM
Klibanov
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D005079:Excipients / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D007477:Ions / Q000737:chemistry; D019999:Pharmaceutical Solutions / Q000737:chemistry*; D012965:Sodium Chloride / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014783:Viscosity / Q000187:drug effects; D014867:Water / Q000737:chemistry
D000911:Antibodies, Monoclonal; D005079:Excipients; D007477:Ions; D019999:Pharmaceutical Solutions; D014867:Water; D012965:Sodium Chloride