Polyethylene Glycol-Induced Precipitation of Interferon Alpha-2a Followed By Vacuum Drying: Development of a Novel Process for Obtaining a Dry, Stable Powder - Oxidation

Polyethylene Glycol-Induced Precipitation of Interferon Alpha-2a Followed By Vacuum Drying: Development of a Novel Process for Obtaining a Dry, Stable Powder
January 26, 2004
Vikas K. Sharma, and Devendra S. Kalonia
AAPS PharmSciTech
Abstract
Feasibility studies were performed on the development of a novel process based on polyethylene glycol (PEG)-induced precipitation of proteins followed by vacuum drying in the presence of sugars to obtain dry protein powders. Apparent solubility of interferon alpha-2a (IFNa2a) was determined in the presence of various PEGs and the effect of solution pH, ionic strength, and temperature was investigated. IFNa2a precipitate was dried at a shelf temperature of 25?C at 100 mTorr either as it is or in the presence of mannitol and/or trehalose. The dried IFNa2a formulations were subjected to accelerated stability studies at 40?C (3 months), and the stability was compared with that of a similar lyophilized formulation. The results indicated that more than 90% of the protein could be precipitated using 10% wt/vol PEG 1450 at pH 6.5 at a solution ionic strength of 71 mM. Vacuum drying of the precipitate only resulted in the formation of insoluble aggregates of IFNa2a; however, this was prevented by the addition of either mannitol or trehalose. The addition of excess mannitol resulted in low residual moisture content and better handling of the final dried product. Accelerated storage stability did not show any aggregation and showed less than 5% formation of oxidized IFNa2a in the dried formulation containing IFNa2a:trehalose:mannitol in a 1:10:100 wt/wt ratio upon storage at 40?C for 3 months. The stability of this vacuum dried formulation was comparable with that of a similar lyophilized formulation.