Stability of interleukin 1 beta (IL-1 beta) in aqueous solution: analytical methods, kinetics, products, and solution formulation implications.
The thermal stability of IL-1 beta in aqueous solution as a function of temperature (5-60 degrees C), pH (2-9), buffer (acetate, citrate, tris, and phosphate), and cyroprotectants (sugars, HSA) was investigated in this study. The analytical methodologies included RP-HPLC, SEC, ELISA, IEF-PAGE, SDS-PAGE, and bioassay. The degradation and inactivation of IL-1 beta at or above 39 degrees C were attributed to autoxidation of the two cysteine residues in the denatured protein, followed by hydrophobic/covalent aggregation and precipitation. At or below 30 degrees C, IEF- and SDS-PAGE results suggest a possible deamidation reaction. The difference in mechanism of degradation precludes the prediction of formulation shelf life from accelerated temperature data. Nonetheless, the good stability observed at 5 degrees C suggests that a solution formulation may be feasible for IL-1 beta.
Gu
L C
LC
Institute of Pharmaceutical Sciences, Syntex Research, Palo Alto, California 94034.
Erdös
E A
EA
Chiang
H S
HS
Calderwood
T
T
Tsai
K
K
Visor
G C
GC
Duffy
J
J
Hsu
W C
WC
Foster
L C
LC
D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D007375:Interleukin-1 / Q000032:analysis / Q000737:chemistry*; D007700:Kinetics; D012996:Solutions; D013696:Temperature; D014867:Water
D007375:Interleukin-1; D012996:Solutions; D014867:Water