title: Characterizing monoclonal antibody formulations in arginine glutamate solutions using1H NMR spectroscopy.
abstract: Assessing how excipients affect the self-association of monoclonal antibodies (mAbs) requires informative and direct in situ measurements for highly concentrated solutions, without sample dilution or perturbation. This study explores the application of solution nuclear magnetic resonance (NMR) spectroscopy for characterization of typical mAb behavior in formulations containing arginine glutamate. The data show that the analysis of signal intensities in 1D1H NMR spectra, when compensated for changes in buffer viscosity, is invaluable for identifying conditions where protein-protein interactions are minimized. NMR-derived molecular translational diffusion rates for concentrated solutions are less useful than transverse relaxation rates as parameters defining optimal formulation. Furthermore, NMR reports on the solution viscosity and mAb aggregation during accelerated stability study assessment, generating data consistent with that acquired by size-exclusion chromatography. The methodology developed here offers NMR spectroscopy as a new tool providing complementary information useful to formulation development of mAbs and other large therapeutic proteins.
authors: a Manchester Institute of Biotechnology, University of Manchester , Manchester , UK.|b School of Chemistry, University of Manchester , Manchester , UK.
authors: Priscilla
authors: P
authors: Kheddo
authors: a Manchester Institute of Biotechnology, University of Manchester , Manchester , UK.
authors: Matthew J
authors: MJ
authors: Cliff
authors: c Formulation Sciences, MedImmune Ltd , Granta Park, Cambridge , UK.
authors: Shahid
authors: S
authors: Uddin
authors: c Formulation Sciences, MedImmune Ltd , Granta Park, Cambridge , UK.
authors: Christopher F
authors: CF
authors: van der Walle
authors: a Manchester Institute of Biotechnology, University of Manchester , Manchester , UK.|b School of Chemistry, University of Manchester , Manchester , UK.
authors: Alexander P
authors: AP
authors: Golovanov
mesh_terms: D000911:Antibodies, Monoclonal / Q000032:analysis* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004151:Dipeptides / Q000032:analysis* / Q000737:chemistry; D004355:Drug Stability; D005079:Excipients / Q000032:analysis* / Q000737:chemistry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D019999:Pharmaceutical Solutions / Q000032:analysis / Q000737:chemistry
chemical_list: D000911:Antibodies, Monoclonal; D004151:Dipeptides; D005079:Excipients; D019999:Pharmaceutical Solutions; C024362:arginine glutamate
keywords: Arginine glutamate; NMR spectroscopy; mAb formulation; mAb stability; reversible self-association