期刊
JOURNAL OF PHARMACEUTICAL SCIENCES
卷 109, 期 9, 页码 2699-2709出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.xphs.2020.05.023
关键词
Osmotic second virial coefficients; Excipients; Biopharmaceuticals; Arginine; Urea; Guanidine hydrochloride; Lysozyme
资金
- BBSRC iCASE studentship award
- AstraZeneca (MedImmune)
Protein-protein interactions are commonly measured in terms of the second osmotic virial coefficient, B-22 from static light scattering (SLS) or the interaction parameter, k(D) from dynamic light scattering (DLS). Often these measurements are carried out at high co-solvent compositions, where correction factors are required for the light scattering analysis. For lysozyme in aqueous solutions containing the co-solvents NaCl, arginine chloride, urea, sucrose or guanidine chloride, we show that B-22 determination requires using in the light scattering equation the refractive index increment of the protein measured at constant solvent chemical potential. Because the increment decreases with increasing co-solvent composition, using a constant value can lead to mis-interpretation of protein-protein interaction trends deduced from the B-22 measurements. Furthermore, there is a contribution to the intensity auto-correlation function measured by dynamic light scattering due to co-solvents. This effect is removed by including longer delay times when fitting the cumulant analysis to determine the diffusion coefficients. We show that an experimentally observed correlation between B-22 and k(D )is recovered once these correction factors have been applied. The findings are particularly relevant to biopharmaceutical industry, where B-22 and kip measurements are used for screening excipient effects in liquid formulations. (C) 2020 American Pharmacists Association (R) . Published by Elsevier Inc. All rights reserved.
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