Downstream processing - Pharmaceutical Biotechnology: Concepts and Aapplications - page 167

Table 6.9 Amino acids, carbohydrates and polyols that have
found most application as stabilizers for some biopharmaceutical
preparations

Amino acids Carbohydrates Polyols

Glycine Glucose Glycerol

Alanine Sucrose Mannitol

Lysine Trehalose Sorbitol

Threonine Maltose PEG

the conformation of some proteins, particularly against heat denaturation. The exact molecular
mechanisms by which such effects are achieved remain to be elucidated.
Several polyols (i.e. molecules displaying multiple hydroxyl groups) have found application
as polypeptide stabilizing agents. Polyols include substances such as glycerol, mannitol, sorbitol
and PEG, as well as inositol ( Table 6.9 and Figure 6.22). A subset of polyols is the carbohydrates,
which are listed separately (and thus somewhat artifi cially) from polyols in Table 6.9. Various
polyols have been found to stabilize proteins in solution directly, and carbohydrates in particular
are also often added to biopharmaceutical products prior to freeze-drying in order to provide
physical bulk to the freeze-dried cake.
Surfactants are well-known protein denaturants. However, when suffi ciently dilute, some sur-
factants (e.g. polysorbate) exert a stabilizing infl uence on some protein types. Proteins display a
tendency to aggregate at interfaces (air—liquid or liquid—liquid), a process that often promotes
their denaturation. Addition of surfactant reduces surface tension of aqueous solutions and of-
ten increases the solubility of proteins dissolved therein. This helps reduce the rate of protein

CH 2 OH CH 2 OH

OH OH

HO H H OH

C C

OH

HO H HO H

C C

H OH H

C OH C OH

HO

H OH H OH

C C

OH

CH 2 OH CH 2 OH

Mannitol Inositol Sorbitol

OH

CH 2

H OH O CH 2 CH 2 OH

C H

n

OH

CH 2

Glycerol Polyethyleneglycol

Figure 6.22 Structure of some polyols that are sometimes used to stabilize proteins