Effects of Histidine and Sucrose on the Biophysical Properties of a Monoclonal Antibody

Youngbin Baek, Nripen Singh, Abhiram Arunkumar, Andrew L. Zydney

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Purpose: Histidine is a commonly used buffer in formulation of monoclonal antibodies (mAb), often with excipients like sucrose. The objective of this study was to examine the effects of both histidine and sucrose on the biophysical characteristics of a mAb. Methods: The hydrodynamic radius of the mAb was determined by dynamic light scattering and confirmed by size exclusion chromatography. Data were also obtained for the osmotic virial coefficients (from osmotic pressure measurements), the solution viscosity, and the mAb thermal stability (using differential scanning calorimetry) at selected conditions. Results: There were no significant changes in mAb conformation / stability as determined by DSC. The hydrodynamic radius initially increased with increasing histidine concentration, going through a maximum at a histidine concentration of about 20 mM. The addition of sucrose increased the mAb hydrodynamic radius at all histidine concentrations by about 0.5 nm. The observed effects of histidine and sucrose on the hydrodynamic radius were also reflected in changes in the osmotic pressure and solution viscosity. Conclusions: These results provide important insights into the effects of both histidine and sucrose on the behavior of concentrated mAb solutions, including the potential impact on ultrafiltration / diafiltration processes.

Original languageEnglish (US)
Pages (from-to)629-639
Number of pages11
JournalPharmaceutical Research
Volume34
Issue number3
DOIs
StatePublished - Mar 1 2017

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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