The Effects of Tween 20 and Sucrose on the Stability of Anti‐L‐Selectin during Lyophilization and Reconstitution
| Autor: | Gerhard Winter, Mark C. Manning, John F. Carpenter, Marie-Luise Hagmann, Theodore W. Randolph, Ulrich Kohnert, Apollon Papadimitriou, LaToya S. Jones |
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| Rok vydání: | 2001 |
| Předmět: |
Protein Folding
Sucrose Polysorbates Pharmaceutical Science Excipient Protein aggregation Protein Structure Secondary Dosage form Excipients chemistry.chemical_compound Freeze-drying Protein structure Drug Stability medicine L-Selectin Guanidine Protein secondary structure Chromatography Spectrum Analysis Antibodies Monoclonal Recombinant Proteins Solutions Freeze Drying chemistry medicine.drug |
| Zdroj: | Journal of Pharmaceutical Sciences. 90:1466-1477 |
| ISSN: | 0022-3549 |
| Popis: | We have chosen an anti-L-selectin antibody as a model protein to investigate the effects of sucrose and/or Tween 20 on protein stability during lyophilization and reconstitution. Native anti-L-selectin secondary structure is substantially retained during lyophilization in the presence of sucrose (1 or 0.125%). However, aggregation of the protein during reconstitution of lyophilized protein powders prepared without sucrose is not reduced by the presence of sucrose in the reconstitution medium. Aggregate formation upon reconstitution is completely inhibited by freeze drying the protein with sucrose and reconstituting with a 0.1% Tween 20 solution. Tween 20 (0.1%) also partially inhibits loss of native anti-L-selectin secondary structure during lyophilization. However, upon reconstitution the formulations lyophilized with Tween 20 contain the highest levels of aggregates. The presence of Tween in only the reconstitution solution appears to inhibit the transition from dimers to higher order oligomers. Potential mechanism(s) for the Tween 20 effects were investigated. However, no evidence of thermodynamic stabilization of anti-L-selectin conformation (e.g., by Tween 20 binding) could be detected. |
| Databáze: | OpenAIRE |
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