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Determination of Protein-Protein Interactions at High Co-Solvent Concentrations Using Static and Dynamic Light Scattering.
Metadata
Journaljournal of pharmaceutical sciences2.997Date
2020 Jun 04
4 months ago
Type
Journal Article
Volume
2020-Sep / 109 : 2699-2709
Author
Holloway L 1, Roche A 1, Marzouk S 1, Uddin S 2, Ke P 3, Ekizoglou S 3, Curtis R 4
Affiliation
  • 2. Formulation Sciences CMC, Immunocore, Milton Park, Abingdon OX14 4RW, United Kingdom.
  • 3. Dosage Form Design & Development, AstraZeneca, Granta Park, Cambridge CB21 6GH, United Kingdom.
  • 4. School of Chemical Engineering and Analytical Science, University of Manchester, M1 7DN, United Kingdom. Electronic address: [email protected]
Doi
PMIDMESH
Abstract
Protein-protein interactions are commonly measured in terms of the second osmotic virial coefficient, B22 from static light scattering (SLS) or the interaction parameter, kD 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 B22 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 B22 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 B22 and kD is recovered once these correction factors have been applied. The findings are particularly relevant to biopharmaceutical industry, where B22 and kD measurements are used for screening excipient effects in liquid formulations.
Keywords: Arginine Biopharmaceuticals Excipients Guanidine hydrochloride Lysozyme Osmotic second virial coefficients Urea
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J Pharm Scijournal of pharmaceutical sciences
Metadata
LocationUnited States
FromELSEVIER SCIENCE INC

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