Comparative effects of stabilizing additives on the rates of heat inactivation of recombinant human interferon alpha-2b in solution.
This study was aimed at the comparative evaluation of stabilizing additives used for the protection of the antiviral activity of interferon-alpha2b against thermal inactivation, at 60 degrees C. The comparative effects of amino acids, polyhydric alcohols, saccharides and nonionic surfactants were studied. All were effective. Representing the thermal inactivation process with first order kinetics, a maximal prolongation of antiviral activity half-life of 39-fold was achieved with the most effective procedure. Inactivation rate constants varied from (53.3+/-4.6)x10(-3) to (2.5+/-0.3)x10(-3) min(-1). Human serum albumin, nonionic surfactants and monosaccharides increased half-life values by 5-39-, 5-23-, 4-20-fold, respectively. Amino acids, polyhydric alcohols and disaccharides increased t(1/2) values by 4-11-, 2-8- and 3-8-fold, respectively. These data provide useful information for the selection of stabilizing additives for IFN-alpha2b formulations.
Sebeka
H K
HK
Institute of Biotechnology, Graiciūno 8, 2028, Vilnius, Lithuania. sereik@ibt.It
Starkuviene
B
B
Trepsiene
O V
OV
Pauliukonis
A A
AA
Bumelis
V A
VA
D000438:Alcohols / Q000494:pharmacology; D000596:Amino Acids / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002461:Cell Line, Transformed; D004187:Disaccharides / Q000494:pharmacology; D004347:Drug Interactions; D004355:Drug Stability; D006207:Half-Life; D006801:Humans; D006863:Hydrogen-Ion Concentration; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D004680:Maus Elberfeld virus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D009005:Monosaccharides / Q000494:pharmacology; D020011:Protective Agents / Q000494:pharmacology*; D011994:Recombinant Proteins; D012709:Serum Albumin / Q000494:pharmacology; D013501:Surface-Active Agents / Q000494:pharmacology
D000438:Alcohols; D000596:Amino Acids; D000998:Antiviral Agents; D004187:Disaccharides; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D009005:Monosaccharides; D020011:Protective Agents; D011994:Recombinant Proteins; D012709:Serum Albumin; D013501:Surface-Active Agents