Can controlled ice nucleation improve freeze-drying of highly-concentrated protein formulations?

J Pharm Sci. 2013 Nov;102(11):3915-9. doi: 10.1002/jps.23704. Epub 2013 Aug 20.

Abstract

The aim of this study was to investigate if controlled ice nucleation with our previouly published method is applicable to highly-concentrated protein formulations of bovine serum albumin (100 mg/ml and 193.9 mg/ml) and a monoclonal antibody (161.2 mg/ml) and if positive effects on primary drying time as well as reconstitution times can be achieved. We observed that for both proteins, ice nucleation at a product temperature of -5 °C significantly reduced primary drying time. Furthermore, reconstitution times of the lyophilized cakes could be shortened, especially for the monoclonal antibody formulation with a reconstitution time of 5 minutes instead of 15 minutes.

Keywords: controlled ice nucleation; dissolution; freeze-drying; lyophilization; proteins; wetting.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry*
  • Cattle
  • Crystallization / methods
  • Excipients / chemistry
  • Freeze Drying / methods*
  • Ice / analysis*
  • Protein Stability*
  • Serum Albumin, Bovine / chemistry*
  • Solubility

Substances

  • Antibodies, Monoclonal
  • Excipients
  • Ice
  • Serum Albumin, Bovine