Reaction kinetics and optimization of the copper-catalyzed oxidation of ApoA-1M

  • Ho S
  • McLaughlin J
  • Thomas K
 et al. 
  • 3

    Readers

    Mendeley users who have this article in their library.
  • 8

    Citations

    Citations of this article.

Abstract

This paper summarizes the development of an optimized Cu(II)-catalyzed oxidation process for the dimer formation of ApoA-1M, the protein component of an HDL mimic with potential efficacy in atherosclerotic plaque reduction. This oxidation represents a major processing step in the large-scale manufacture of ApoA-1M dimer. The development approach utilizes reaction kinetic modeling, design of experiment, and neural network analysis to establish a quantitative basis for specification of process operating ranges. This work is thus an example of quality by design (QbD) principles where a systematic mechanistic understanding combined with multivariate analysis is integral to process development. Operating within the defined optimum window of operation resulted in both enhanced performance and robustness for the oxidation step in the piloting and manufacturing campaigns. © 2009 Elsevier Ltd. All rights reserved.

Author-supplied keywords

  • Apolipoprotein
  • Catalysis
  • Pharmaceuticals
  • Process optimization
  • Protein oxidation
  • Quality by design
  • Reaction kinetics

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Sa V. Ho

  • Joseph K. McLaughlin

  • Kristen E. Thomas

  • Eric Suda

  • John T. Herberg

  • Robert L. Dufield

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free