Screening of novel excipients for freeze-dried protein formulations
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Screening of novel excipients for freeze-dried protein formulations. / Holm, Tobias Palle; Meng-Lund, Helena; Rantanen, Jukka; Jorgensen, Lene; Grohganz, Holger.
In: European Journal of Pharmaceutics and Biopharmaceutics, Vol. 160, 2021, p. 55-64.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Screening of novel excipients for freeze-dried protein formulations
AU - Holm, Tobias Palle
AU - Meng-Lund, Helena
AU - Rantanen, Jukka
AU - Jorgensen, Lene
AU - Grohganz, Holger
PY - 2021
Y1 - 2021
N2 - The typical excipients used as bulking agents and lyoprotectants for freeze-drying are usually limited to only a few selected substances, such as sucrose and mannitol. Considering the sheer diversity amongst proteins, it is doubtful that this limited choice should, in every case, provide the best possible option in order to achieve the most stable product. In this work, a screening of 12 proteins with 64 excipients was conducted in order to increase the knowledge space of potential excipients. Three critical quality attributes (CQAs) of the freeze-dried products, namely the solid state, the cake appearance and the protein integrity based on changes in tryptophan fluorescence were investigated by high throughput X-ray powder diffraction, image analysis and intrinsic fluorescence spectroscopy, respectively. It was found, that in some cases the excipient had a dominating influence on the CQAs, whilst in other cases the CQAs were primarily protein dependent, or that the CQAs were dependent on the combination of both. In the course of this investigation, a general view of potentially relevant excipients, and their interplay with various proteins, was obtained, thereby furthermore paving the way for the use of novel freeze-drying excipients.
AB - The typical excipients used as bulking agents and lyoprotectants for freeze-drying are usually limited to only a few selected substances, such as sucrose and mannitol. Considering the sheer diversity amongst proteins, it is doubtful that this limited choice should, in every case, provide the best possible option in order to achieve the most stable product. In this work, a screening of 12 proteins with 64 excipients was conducted in order to increase the knowledge space of potential excipients. Three critical quality attributes (CQAs) of the freeze-dried products, namely the solid state, the cake appearance and the protein integrity based on changes in tryptophan fluorescence were investigated by high throughput X-ray powder diffraction, image analysis and intrinsic fluorescence spectroscopy, respectively. It was found, that in some cases the excipient had a dominating influence on the CQAs, whilst in other cases the CQAs were primarily protein dependent, or that the CQAs were dependent on the combination of both. In the course of this investigation, a general view of potentially relevant excipients, and their interplay with various proteins, was obtained, thereby furthermore paving the way for the use of novel freeze-drying excipients.
KW - Excipients
KW - Formulation development
KW - Freeze-drying
KW - High throughput
KW - Image analysis
KW - Intrinsic fluorescence spectroscopy
KW - Protein stability
KW - Solid state analysis
U2 - 10.1016/j.ejpb.2021.01.008
DO - 10.1016/j.ejpb.2021.01.008
M3 - Journal article
C2 - 33508435
AN - SCOPUS:85100060660
VL - 160
SP - 55
EP - 64
JO - European Journal of Pharmaceutics and Biopharmaceutics
JF - European Journal of Pharmaceutics and Biopharmaceutics
SN - 0939-6411
ER -
ID: 259823225