The Influence of Arginine and Counter-Ions: Antibody Stability during Freeze-Drying.

Amino acids, for example L-arginine, are used in lyophilisation as crystalline bulking, buffering, viscosity reducing or stabilising excipients. In this study, arginine was formulated with different counter ions (hydrochloride, citrate, lactobionate, phosphate, and succinate). A monoclonal antibody was investigated in sugar-free arginine formulations and mixtures with sucrose regarding cake appearance and protein aggregation and fragmentation.

The effect of residual moisture on a monoclonal antibody stability in L-arginine based lyophilisates.

Amino acids are not only used as buffering agents in lyophilisation, but also exhibit cryo- and lyoprotecting characteristics. L-Arginine based lyophilisates were tested regarding their ability to stabilise a monoclonal antibody (mAb) at different residual moisture (RM) levels. Arginine base was formulated with citric, hydrochloric, lactobionic, phosphoric, and succinic acid for pH adjustment.

Improvement of arginine hydrochloride based antibody lyophilisates.

Arginine hydrochloride (ArgHCl) can be used as stabiliser of protein drugs in both liquid and freeze dried formulations reducing aggregation. But ArgHCl exhibits a low T' value which can lead to cake collapse during lyophilisation. We analysed arginine (Arg) citrate hydrochloride and lactobionate based lyophilisates aiming for elegant cake appearance in combination with minimal protein aggregation using 2 mg/ml monoclonal antibody (mAb) without additional excipients and in combination with sucrose (Suc) as amorphous stabiliser as well as mannitol (Man) and phenylalanine (Phe) as crystalline bulking agents.

Freeze concentration during freezing: How does the maximally freeze concentrated solution influence protein stability?

During freeze drying of biologics, a highly viscous freeze concentrate (FC) is formed upon the initial freezing due to the crystallisation of ice. Protein stability in this freeze concentrated phase is not yet well understood, but can decide upon the success of the lyophilisation itself. Protein stability may be high below the T' as it is typically the case during primary drying but decreases above T', e.

Method development and analysis of the water content of the maximally freeze concentrated solution suitable for protein lyophilisation.

During freeze-drying of a liquid formulation, a freeze-concentrate is formed in the first phase, the freezing step. Understanding the composition of the maximally freeze concentrated solution can help to judge the process stability of biopharmaceuticals during lyophilisation. Our objective was to develop a suitable method to determine the water content of the maximally freeze concentrated solution using differential scanning calorimetry (DSC).