Freeze/thaw of IGG solutions
In this communication, the effect of mannitol and trehalose crystallization on the unfolding of IgG1, 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.
Jacqueline Horn, Sampeeti Jena, Alptekin Aksan, Wolfgang Friess,
Freeze/thaw of IGG solutions,
European Journal of Pharmaceutics and Biopharmaceutics, Volume 134, 2019, Pages 185-189,
ISSN 0939-6411,
https://doi.org/10.1016/j.ejpb.2018.12.001.