Drug Discovery & Development

Presentations

Contribution of Variable Domains to the Stability of Humanized IgG1 Monoclonal Antibodies

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Therapeutic Proteins: Solution Behavior During Pre-Formulation and Formulation Development

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Favorable Entropic Influence of Urea Stabilizes Against Thermal Unfolding-Mediated Aggregation of rhuIL-1R

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The Sweetness of Thermal Stability: Using DSC to Probe Increases in Thermal Stability from the Addition of Polyols

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The Application of Capillary DSC in a Contract Development Organization

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Assessing the Effects of Excipients and Excipient Screening

To arrive at the correct liquid formulation quickly is of paramount concern for the biopharmaceutical industry.  Understanding the effects of the excipients in a formulation will greatly affect the final formulation.  Both Differential Scanning Calorimetry (DSC) and Isothermal Titration Calorimetry (ITC) can aid in understanding the effects that excipients have on final formulations.  DSC enables rapid, accurate and easy to perform measurements of the stability contribution of individual excipients as well as identify the mechanism of stabilization for a particular biotherapeutic. ITC aids in the identification of the mechanism of stabilization by characterizing the binding of excipients used in a formulation. 

DSC can aid in understanding the effects that excipients have on final formulations as well as the stability contribution of individual excipients. This information can also aid in identifying the mechanism of stabilization for a particular biotherapeutic. In the example shown above, DSC was used to identify multiple stabilization trends occurring over a broad concentration range of tested excipient (Data and images courtesy of Nick Guziewicz, Genzyme).

Why use microcalorimetry for excipient screening during formulations development?

  • Easily determine the stability contribution of individual excipients with DSC
  • Fully characterize excipient binding
  • Aid in identifying and understanding the mechanism of stabilization.

References

DSC-Liquid Protein Formulations Studies Reference List

Analytical Techniques for Biopharmaceutical Development
Roberto Rodriguez-Diaz, Tim Wehr, Stephen Tuck, editors,
Taylor & Francis (2005)

  • Chapter 13 – Microcalorimetric Approaches to Biopharmaceutical Development (written by Richard L. Remmele, Jr.)

Interleukin-1 receptor (IL-1R) Liquid Formulation Development Using Differential Scanning Calorimetry
Richard L. Remmele, Jr., Nancy L. Nightlinger, Subhashini Srinivasan, and Wayne R. Gombotz,
Pharmaceutical Research, Volume 15, 200-208 (1998)

Scan-Rate-Dependant Melting Transitions of Interleukin-1 Receptor (Type II): Elucidation of Meaningful Thermodynamic and Kinetic Parameters of Aggregation Acquired from DSC Simulations
Richard L. Remmele, Jr., Jian Zhang-van Enk, Vasu Dharmavaram, David Balaban, Mark Durst, Alex Shoshitaishvili, and Hugh Rand
Journal of the American Chemical Society, Volume 127, 8328-8339 (2005)

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