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Investigating thermally induced aggregation of Somatropin- new insights using orthogonal techniques
RISE Research Institutes of Sweden, Bioeconomy and Health, Chemical Process and Pharmaceutical Development. Lund University, Sweden.ORCID iD: 0000-0001-7418-5587
Lund University, Sweden.
Solve Research & Consultancy, Sweden.
Lund University, Sweden.
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2023 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 637, article id 122829Article in journal (Refereed) Published
Abstract [en]

Three orthogonal techniques were used to provide new insights into thermally induced aggregation of the therapeutic protein Somatropin at pH 5.8 and 7.0. The techniques were Dynamic Light Scattering (DLS), Asymmetric Flow-Field Flow-Fractionation (AF4), and the TEM-based analysis system MiniTEM™. In addition, Differential Scanning Calorimetry (DSC) was used to study the thermal unfolding and stability. DSC and DLS were used to explain the initial aggregation process and aggregation rate at the two pH values. The results suggest that less electrostatic stabilization seems to be the main reason for the faster initial aggregation at pH 5.8, i.e., closer to the isoelectric point of Somatropin. AF4 and MiniTEM were used to investigate the aggregation pathway further. Combining the results allowed us to demonstrate Somatropin's thermal aggregation pathway at pH 7.0. The growth of the aggregates appears to follow two steps. Smaller elongated aggregates are formed in the first step, possibly initiated by partly unfolded species. In the second step, occurring during longer heating, the smaller aggregates assemble into larger aggregates with more complex structures. © 2023 The Author(s)

Place, publisher, year, edition, pages
Elsevier B.V. , 2023. Vol. 637, article id 122829
Keywords [en]
human growth hormone, differential scanning calorimetry, photon correlation spectroscopy, Calorimetry, Differential Scanning, Dynamic Light Scattering
National Category
Physical Chemistry
Identifiers
URN: urn:nbn:se:ri:diva-64673DOI: 10.1016/j.ijpharm.2023.122829Scopus ID: 2-s2.0-85151369842OAI: oai:DiVA.org:ri-64673DiVA, id: diva2:1757001
Note

Correspondence Address: Västberg, A.; Research Institutes of Sweden, Drottning Kristinas väg 61B, Sweden; email: amanda.vastberg@ri.se; Funding details: VINNOVA, 2018-04730; Funding text 1: The authors thank Malvern Analytical AB for the opportunity to use their automated PEAQ DSC and Zetasizer Ultra instruments, and especially thanks to Dr. Natalia Markova for valuable discussions on the DSC measurements and data, and Dr. Hanna Jankevics-Jones for valuable discussions on the DLS measurements and data. This research was funded by the Swedish Governmental Agency for Innovation Systems (VINNOVA) Research Council trough the competence center NextBioForm under grant number 2018-04730.; Funding text 2: This research was funded by the Swedish Governmental Agency for Innovation Systems (VINNOVA) Research Council trough the competence center NextBioForm under grant number 2018-04730.

Available from: 2023-05-15 Created: 2023-05-15 Last updated: 2024-05-22Bibliographically approved

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Västberg, AmandaElofsson, Ulla

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