Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2486163 | Journal of Pharmaceutical Sciences | 2011 | 14 Pages |
Abstract
Aqueous extractables/leachables from three sterilizingâgrade filter membranes [polyvinylidene fluoride (PVDF), polyethersulfone (PES), and mixed cellulose ester (MCE)] were found to significantly reduce the surface tension of aqueous solutions. To evaluate the effect of these extractables/leachables from filter membranes on stability of protein formulations, model IgG2 formulations (with or without added surfactant) were spiked with different levels of filter extractables from stock solutions as a stress study. The stock solutions of extractables were created by processing the filter membranes through autoclaving and soaking steps. The IgG2 formulations were subsequently subject to agitation and temperature stress. Extractables/leachables from the filters were found to have a significant protective (PVDF, PES) and destabilizing (MCE) impact on both visible and subvisible particulates formation under agitation stress for formulations that did not contain any additional surfactant such as polysorbate 80. The impact of filter extractables/leachables on chemical stability of the antibody formulation displayed a more complicated pattern, but was generally destabilizing, causing increases in aggregation, oxidation, and acidic species. In conclusion, extractables/leachables from filter membranes may have impact on protein formulation stability and caution should be exercised during protein filtration, especially when filtering small volumes and in preformulation or highâthroughput screening studies. © 2011 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 100:4617-4630, 2011
Keywords
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Pharmacology, Toxicology and Pharmaceutical Science
Drug Discovery
Authors
Min Huang, Teresa S. Horwitz, Cindy Zweiben, Satish K. Singh,