Intra-Micellar and Extra-Micellar Oxidation in Phosphate and Histidine Buffers Containing Polysorbate 80
Björn-Hendrik Peters1, Yangjie Wei1, C Russell Middaugh1
1Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, KS 66047.
Journal of Pharmaceutical Sciences
|June 18, 2022
Summary
Polysorbate excipients in protein drugs can degrade via oxidation both inside and outside micelles. This study quanties polysorbate oxidation in common pharmaceutical buffers, finding similar degradation rates in both compartments.
Area of Science:
- Pharmaceutical science
- Biochemistry
- Physical chemistry
Background:
- Polysorbate is crucial for stabilizing therapeutic protein formulations by preventing aggregation.
- Oxidative degradation can compromise the stability of both polysorbate and therapeutic proteins.
- Understanding polysorbate oxidation within micelles is vital for drug formulation stability.
Purpose of the Study:
- To quantitatively assess the extent of polysorbate oxidation within and outside micelles.
- To investigate polysorbate oxidation in pharmaceutically relevant buffer systems.
- To compare intra- and extra-micellar oxidation rates in different buffers.
Main Methods:
- Utilized 2,2'-azobis(2-methylpropionamidine)dihydrochloride (AAPH) as a peroxyl radical initiator.
- Employed C11-BODIPY(581/591), a lipid peroxidation probe, for detection.
- Applied fluorescence spectroscopy to quantify oxidation levels.
Main Results:
- Demonstrated that both intra- and extra-micellar oxidation of polysorbate occur.
- Observed polysorbate oxidation in pharmaceutically relevant phosphate and histidine buffers.
- Found that the relative extent of intra- and extra-micellar oxidation is similar across buffer systems.
Conclusions:
- Polysorbate oxidation is a significant concern in therapeutic protein formulations.
- Both micellar and non-micellar polysorbate are susceptible to oxidative degradation.
- Buffer composition does not significantly alter the relative distribution of polysorbate oxidation.
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