title: Can controlled ice nucleation improve freeze-drying of highly-concentrated protein formulations?
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.
authors: Department of Pharmacy, Ludwig Maximilians University of Munich, Munich, 81377, Germany.
authors: Raimund
authors: R
authors: Geidobler
authors: Ilona
authors: I
authors: Konrad
authors: Gerhard
authors: G
authors: Winter
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D002417:Cattle; D003460:Crystallization / Q000379:methods; D005079:Excipients / Q000737:chemistry; D005612:Freeze Drying / Q000379:methods*; D007053:Ice / Q000032:analysis*; D055550:Protein Stability; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D012995:Solubility
chemical_list: D000911:Antibodies, Monoclonal; D005079:Excipients; D007053:Ice; D012710:Serum Albumin, Bovine
keywords: controlled ice nucleation; dissolution; freeze-drying; lyophilization; proteins; wetting