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Buffer formulation
change
When it's used
pH • Will change electrostatic properties of the molecule
• Potential change to r
H
because of changes in solvent shell
• Affects solubility (generally want to be >1 pH away from pI) and
therefore affect aggregation/PDI
Salt concentration
• Increase solubility by increasing the ionic strength of solution
• Too high can induce self-association ("salting-out")
Additives
• Certain ions or small molecules are stabilizing (e.g. Mg
2+
for
nucleic-acid binding proteins, EDTA to prevent degradation)
• Adjuvants might be necessary to improve response in patients,
and must be considered as part of the formulation process
• Sugars (sucrose) can enhance stability with protective "shell"
Detergents
• Proteins with hydrophobic regions will have increased solubility
and decreased aggregation
Glycerol
• Used for long-term storage to decreases freezing damage from
water molecules in solution
How might my buffers affect stability?
