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Chapter 7: An Empirical Phase Diagram: High-Throughput Screening Approach to the Characterization and Formulation of Biopharmaceuticals

  • Yangjie Wei
  • Sangeeta B. Joshi
  • Akhilesh Bhambhani
  • Yuhong Zeng
  • Nicholas R. Larson
  • Gang Hu
  • Eric J. Deeds
  • C. Russell MiddaughEmail author
Chapter
  • 95 Downloads
Part of the AAPS Advances in the Pharmaceutical Sciences Series book series (AAPS, volume 35)

Abstract

The complexity of proteins usually requires the use of multiple, moderate resolution experimental techniques to provide an information-rich picture of their structure and stability. Here we describe a technique known as the empirical phase diagram (EPD), which can be used to present such multidimensional data in picture form. Data from various spectroscopic, hydrodynamic, and calorimetric methods, among others, are created in matrix form and converted to a colored picture as a function of variables such as temperature, pH, ionic strength, etc. Additional methods such as radar charts and Chernoff faces are also discussed. The use of EPDs in the characterization and formulation of biomolecules is described. Further methods based on machine learning are also considered. A wide range of examples are employed to illustrate the power and utility of these approaches.

Keywords

Empirical phase diagram (EPD) Biologics Formulation screening Stability Biophysical characterization Radar chart Chernoff face Machine learning 

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Copyright information

© American Association of Pharmaceutical Scientists 2020

Authors and Affiliations

  • Yangjie Wei
    • 1
  • Sangeeta B. Joshi
    • 1
  • Akhilesh Bhambhani
    • 1
    • 2
  • Yuhong Zeng
    • 1
    • 3
  • Nicholas R. Larson
    • 1
  • Gang Hu
    • 1
  • Eric J. Deeds
    • 4
    • 5
  • C. Russell Middaugh
    • 1
    Email author
  1. 1.Department of Pharmaceutical ChemistryMacromolecule and Vaccine Stabilization Center, University of KansasLawrenceUSA
  2. 2.Merck & Co. Inc.West PointUSA
  3. 3.ReForm BiologicsWoburnUSA
  4. 4.Department of Molecular BiosciencesUniversity of KansasLawrenceUSA
  5. 5.Center for Computational BiologyUniversity of KansasLawrenceUSA

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