Monitoring of the sedimentation kinetics of vaccine adjuvants using water proton NMR relaxation

Magn Reson Chem. 2021 Feb;59(2):147-161. doi: 10.1002/mrc.5096. Epub 2020 Sep 16.


Suspensions of solid particles find applications in many areas-mining, waste treatment, and in pharmaceutical formulations. Pharmaceutical suspensions include aluminum-adjuvanted vaccines are widely administered to millions of people worldwide annually. Hence, the stability parameters of such suspensions, for example, sedimentation rate and the compactness of the formed sediments, are of great interest to achieve the most optimal and stable formulations. Unlike currently used analytical techniques involving visual observations and/or monitoring of several optical properties using specialized glassware, water proton nuclear magnetic resonance (wNMR) used in this work allows one to analyze samples in their original sealed container regardless of its opacity and/or labeling. It was demonstrated that the water proton transverse relaxation rate could be used to monitor in real time the sedimentation process of two widely used aluminum adjuvants-Alhydrogel® and Adju-Phos®. Using wNMR, we obtained valuable information on the sedimentation rate, dynamics of the supernatant and sediment formation, and the sedimentation volume ratio (SVR) reflecting the compactness of the formed sediment. Results on SVR from wNMR were verified by caliper measurements. Verification of the sedimentation rate results from wNMR by other analytical techniques is challenging due to differences in the measured attributes and even units of the reported rate. Nonetheless, our results demonstrate the practical applicability of wNMR as an analytical tool to study pharmaceutical suspensions, for example, aluminum-adjuvanted vaccines, to provide higher quality and more efficient vaccines. Such analyses could be carried out in the original container of a suspension drug product to study its colloidal stability and to monitor its quality over time without compromising product integrity.

Keywords: aluminum adjuvants; sediment; sedimentation rate; sedimentation volume ratio (SVR); supernatant; water proton transverse relaxation rate (R2(T)).

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adjuvants, Immunologic / chemistry*
  • Aluminum Compounds / chemistry*
  • Aluminum Hydroxide / chemistry*
  • Kinetics
  • Phosphates / chemistry*
  • Physical Phenomena
  • Proton Magnetic Resonance Spectroscopy
  • Water / chemistry*


  • Adjuvants, Immunologic
  • Aluminum Compounds
  • Phosphates
  • Water
  • Aluminum Hydroxide
  • aluminum phosphate