Influence of water and trehalose on α- and β-relaxation of freeze-dried lysozyme formulations
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Influence of water and trehalose on α- and β-relaxation of freeze-dried lysozyme formulations. / Vallaster, Bernadette; Engelsing, Florian; Grohganz, Holger.
In: European Journal of Pharmaceutics and Biopharmaceutics, Vol. 194, 2024, p. 1-8.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Influence of water and trehalose on α- and β-relaxation of freeze-dried lysozyme formulations
AU - Vallaster, Bernadette
AU - Engelsing, Florian
AU - Grohganz, Holger
N1 - Publisher Copyright: © 2023 The Author(s)
PY - 2024
Y1 - 2024
N2 - Molecular mobility in form of alpha and beta relaxations is considered crucial for characterization of amorphous lyophilizates and reflected in the transition temperatures Tgα and Tgβ. Based on an overview of applied methods to study beta relaxations, Dynamic Mechanical analysis was used to measure Tgα and Tgβ in amorphous freeze-dried samples. Lysozyme and trehalose as well as their mixtures in varying ratios were investigated. Three different residual moisture levels, ranging from roughly 0.5–7 % (w/w), were prepared via equilibration of the freeze-dried samples. Known plasticising effects of water on Tgα were confirmed, also via differential scanning calorimetry. In addition and contrary to expectations, an influence of water on the Tgβ also was observed. On the other hand, an increasing amount of trehalose lowered Tgα but increased Tgβ showing that Tgα and Tgβ are not paired. The findings were interpreted with regard to their underlying molecular mechanisms and a correlation with the known influences of water and trehalose on stability. The results provide encouraging hints for future stability studies of freeze-dried protein formulations, which are urgently needed, not least for reasons of sustainability.
AB - Molecular mobility in form of alpha and beta relaxations is considered crucial for characterization of amorphous lyophilizates and reflected in the transition temperatures Tgα and Tgβ. Based on an overview of applied methods to study beta relaxations, Dynamic Mechanical analysis was used to measure Tgα and Tgβ in amorphous freeze-dried samples. Lysozyme and trehalose as well as their mixtures in varying ratios were investigated. Three different residual moisture levels, ranging from roughly 0.5–7 % (w/w), were prepared via equilibration of the freeze-dried samples. Known plasticising effects of water on Tgα were confirmed, also via differential scanning calorimetry. In addition and contrary to expectations, an influence of water on the Tgβ also was observed. On the other hand, an increasing amount of trehalose lowered Tgα but increased Tgβ showing that Tgα and Tgβ are not paired. The findings were interpreted with regard to their underlying molecular mechanisms and a correlation with the known influences of water and trehalose on stability. The results provide encouraging hints for future stability studies of freeze-dried protein formulations, which are urgently needed, not least for reasons of sustainability.
KW - Beta relaxation
KW - Dynamic mechanical analysis
KW - Molecular mobility
KW - Water content
U2 - 10.1016/j.ejpb.2023.11.019
DO - 10.1016/j.ejpb.2023.11.019
M3 - Journal article
C2 - 38029940
AN - SCOPUS:85178463166
VL - 194
SP - 1
EP - 8
JO - European Journal of Pharmaceutics and Biopharmaceutics
JF - European Journal of Pharmaceutics and Biopharmaceutics
SN - 0939-6411
ER -
ID: 378753026