High concentration formulations of recombinant human interleukin-1 receptor antagonist: II. Aggregation kinetics
High concentration formulations of recombinant human interleukin-1 receptor antagonist: II. Aggregation kinetics
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DOI:
10.1002/jps.21205
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发表时间:
2008-08-01
影响因子:
3.8
通讯作者:
Randolph, Theodore W.
中科院分区:
文献类型:
--
作者:
Alford, John R.;Kendrick, Brent S.;Randolph, Theodore W.
At high protein concentrations (i.e., 50-100 mg/mL) and 37 degrees C, low solution ionic strength accelerates aggregation of recombinant human interleukin-1 receptor antagonist (rhIL-1ra). We have used a variety of physical and spectroscopic techniques to explain this observation. A population balance model was applied to a continuous mixed suspension, mixed product removal (MSMPR) reactor at steady-state to determine aggregate nucleation and growth rates. Nucleation rates increase at low ionic strength, while growth rates are unaffected. At low rhIL-1ra concentrations (i.e.,