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dc.contributor.authorRandolph, Theodore W.
dc.contributor.authorSchiltz, Elise
dc.contributor.authorSederstorm, Donn
dc.contributor.authorSteinmann, Daniel
dc.contributor.authorMozziconacci, Olivier
dc.contributor.authorSchöneich, Christian
dc.contributor.authorFreund, Erwin
dc.contributor.authorRicci, Margaret S.
dc.contributor.authorCarpenter, John F.
dc.contributor.authorLengsfeld, Corrine S.
dc.date.accessioned2017-04-20T18:53:12Z
dc.date.available2017-04-20T18:53:12Z
dc.date.issued2015-02
dc.identifier.citationRandolph, T. W., Schiltz, E., Sederstrom, D., Steinmann, D., Mozziconacci, O., Schöneich, C., … Lengsfeld, C. S. (2015). DO NOT DROP: MECHANICAL SHOCK IN VIALS CAUSES CAVITATION, PROTEIN AGGREGATION AND PARTICLE FORMATION. Journal of Pharmaceutical Sciences, 104(2), 602–611. http://doi.org/10.1002/jps.24259en_US
dc.identifier.urihttp://hdl.handle.net/1808/23758
dc.description.abstractIndustry experience suggests that g-forces sustained when vials containing protein formulations are accidentally dropped can cause aggregation and particle formation. To study this phenomenon, a shock tower was used to apply controlled g-forces to glass vials containing formulations of two monoclonal antibodies and recombinant human growth hormone (rhGH). High-speed video analysis showed cavitation bubbles forming within 30 μs and subsequently collapsing in the formulations. As a result of echoing shock waves, bubbles collapsed and reappeared periodically over a millisecond timecourse. Fluid mechanics simulations showed low-pressure regions within the fluid where cavitation would be favored. A hydroxyphenylfluorescein assay determined that cavitation produced hydroxyl radicals. When mechanical shock was applied to vials containing protein formulations, gelatinous particles appeared on the vial walls. Size exclusion chromatographic analysis of the formulations after shock did not detect changes in monomer or soluble aggregate concentrations. However, subvisible particle counts determined by microflow image analysis increased. The mass of protein attached to the vial walls increased with increasing drop height. Both protein in bulk solution and protein that became attached to the vial walls after shock were analyzed by mass spectrometry. rhGH recovered from the vial walls in some samples revealed oxidation of Met and/or Trp residues.en_US
dc.publisherElsevieren_US
dc.rightsThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 4.0 (CC BY-NC-ND 4.0), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.en_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.titleDo not drop: Mechanical shock in vials causes cavitation, protein aggregation and particle formationen_US
dc.typeArticleen_US
kusw.kuauthorSteinmann, Daniel
kusw.kuauthorMozziconacci, Olivier
kusw.kuauthorSchöneich, Christian
kusw.kudepartmentPharmaceutical Chemistryen_US
dc.identifier.doi10.1002/jps.24259en_US
kusw.oaversionScholarly/refereed, author accepted manuscripten_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US
dc.rights.accessrightsopenAccess


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This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 4.0 (CC BY-NC-ND 4.0), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Except where otherwise noted, this item's license is described as: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 4.0 (CC BY-NC-ND 4.0), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.