RT Journal Article
SR Electronic
T1 The Effects of Various Excipients on the Unfolding of Basic Fibroblast Growth Factor
JF PDA Journal of Pharmaceutical Science and Technology
JO PDA J Pharm Sci Technol
FD Parenteral Drug Association (PDA)
SP 209
OP 214
VO 52
IS 5
A1 Dipesh Shah
A1 Thomas P. Johnston
A1 Sabine Heitz
A1 Ashim K. Mitra
YR 1998
UL http://journal.pda.org/content/52/5/209.abstract
AB The purpose of this study was to determine the effects of various pharmaceutical additives on temperature and chaotrope-induced (guanidine HCl = GnHCl) denaturation of basic fibroblast growth factor (bFGF). The effect of various pharmaceutical additives on the stability (tertiary structure) of bFGF was assessed using fluorescence spectroscopy. An increase in the hydrophobicity of anionic surfactants (alkyl sulfonates) incubated with bFGF were shown to retard thermal-induced denaturation of bFGF. Increasing the concentration of decane sulfonate in an aqueous bFGF solution decreased the rate and extent of GnHCl-induced denaturation and demonstrated no inherent capacity to significantly alter the conformation of bFGF by itself. Structural differences in surfactants (e.g., aromatic, heterocyclics and straight-chain alkyl compounds) resulted in differences in the rate and extent of thermal-induced denaturation of bFGF. An increase in the concentration of citrate buffer increased the rate and extent of thermal-induced denaturation of bFGF. Results suggest that various excipients may affect the rate and extent of bFGF unfolding induced by chemical or thermal stress. Ionic charge and the degree of lipophilicity of an additive may significantly affect the rate and extent of the unfolding process.