Abstract：
:Industry 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 time course. 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.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Randolph TW,Schiltz E,Sederstrom D,Steinmann D,Mozziconacci O,Schöneich C,Freund E,Ricci MS,Carpenter JF,Lengsfeld CSdoi
10.1002/jps.24259subject
Has Abstractpub_date
2015-02-01 00:00:00pages
602-11issue
2eissn
0022-3549issn
1520-6017pii
S0022-3549(15)30221-5journal_volume
104pub_type
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