In this communication, the effect of mannitol and trehalose crystallization on the unfolding of IgG 1 , a monoclonal antibody, in the frozen state with repeat freeze/thaw under different pH conditions was explored. Formulations were annealed at −20 °C for 20 h five times (interrupted by freeze/thaw). This was done to induce excipient crystallization. Characterization of the frozen-thawed samples was performed by circular dichroism, particle analysis, and size exclusion chromatography. At a pH of 3, formation of insoluble and soluble aggregates was observed however, these could be reduced by the use of a surfactant. Cryoprotectant free formulations showed higher monomer content after freeze/thaw. At pH 5, a single freeze/thaw cycle did not result in a significant increase in particle numbers. At pH range of 4–7 however, aggregate formation in the size range of 1–25 µm was observed after 5 freeze/thaw cycles.
|Original language||English (US)|
|Number of pages||5|
|Journal||European Journal of Pharmaceutics and Biopharmaceutics|
|State||Published - Jan 2019|
Bibliographical noteFunding Information:
This work was partially funded by an NSF grant ( CBET-1335936 ) to AA.
This work was partially funded by an NSF grant (CBET-1335936) to AA.
© 2018 Elsevier B.V.
Copyright 2019 Elsevier B.V., All rights reserved.
- Monoclonal antibody