Room Temperature Intrinsic Emission Ratio of BSA Correlates With Percent Aggregates During Long-Term Storage
Copyright © 2020 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved..
Successful formulation development hinges on the ability to screen and identify excipients that stabilize drug products during long-term storage. Biophysical and accelerated stability studies are used to screen for excipients that stabilize protein drug products. However, these studies are not always predictive of aggregation during long-term storage. In this study, we used multivariate experimentation to compare the effectiveness of intrinsic fluorescence and size exclusion chromatography accelerated stability parameters to predict excipients that stabilized bovine serum albumin (BSA) against aggregation on long-term storage at 4 °C. Emission intensity ratio (IR330/350) data was more sensitive than emission maxima (λmax) or intensity measurements in identifying significant factors and interactions. We observed the expected inverse correlation between the mid-points of fluorescence thermal transitions (Tms) and insoluble aggregates at 4 and 40 °C. However, there were positive correlations between Tms and % aggregates at 4 °C, indicating that if Tm was used as a predictive tool, it would select formulations that promoted soluble aggregates on long-term storage. Ambient temperature IR330/350 measurements identified excipients that reduced BSA soluble aggregates on long-term storage. The results show ambient temperature emission ratio measurements can be useful for protein formulation development.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:110 |
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| Enthalten in: |
Journal of pharmaceutical sciences - 110(2021), 3 vom: 08. März, Seite 1120-1129 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Manrrique, Joel D [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 17.06.2021 Date Revised 17.06.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.xphs.2020.10.045 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM31695912X |
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| 520 | |a Copyright © 2020 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Successful formulation development hinges on the ability to screen and identify excipients that stabilize drug products during long-term storage. Biophysical and accelerated stability studies are used to screen for excipients that stabilize protein drug products. However, these studies are not always predictive of aggregation during long-term storage. In this study, we used multivariate experimentation to compare the effectiveness of intrinsic fluorescence and size exclusion chromatography accelerated stability parameters to predict excipients that stabilized bovine serum albumin (BSA) against aggregation on long-term storage at 4 °C. Emission intensity ratio (IR330/350) data was more sensitive than emission maxima (λmax) or intensity measurements in identifying significant factors and interactions. We observed the expected inverse correlation between the mid-points of fluorescence thermal transitions (Tms) and insoluble aggregates at 4 and 40 °C. However, there were positive correlations between Tms and % aggregates at 4 °C, indicating that if Tm was used as a predictive tool, it would select formulations that promoted soluble aggregates on long-term storage. Ambient temperature IR330/350 measurements identified excipients that reduced BSA soluble aggregates on long-term storage. The results show ambient temperature emission ratio measurements can be useful for protein formulation development | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Albumin | |
| 650 | 4 | |a Biopharmaceutical characterization | |
| 650 | 4 | |a Chromatography | |
| 650 | 4 | |a Circular dichroism | |
| 650 | 4 | |a Factorial design | |
| 650 | 4 | |a Fluorescence spectroscopy | |
| 650 | 4 | |a Protein aggregation | |
| 650 | 4 | |a Protein formulation | |
| 650 | 4 | |a Thermal analysis | |
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| 650 | 7 | |a Serum Albumin, Bovine |2 NLM | |
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| 700 | 1 | |a Franklin, Cynthia E |e verfasserin |4 aut | |
| 700 | 1 | |a Coker, Adeola O |e verfasserin |4 aut | |
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