Can Controlled Ice Nucleation Improve Freeze‐Drying of Highly‐Concentrated Protein Formulations?

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. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:3915-3919, 2013