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. Lyophilisates with less than 0.5% and approx. 2.5%RM were stored for up to 6 months at 40 °C. The mAb aggregation in arginine in combination with hydrochloric acid and succinic acid was similar or even less compared to a sucrose reference formulation. Arginine in combination with citric acid, lactobionic acid, and phosphoric acid resulted in lower protein stability. Overall, arginine formulations with high RM levels resulted in better protein stabilisation despite decreased glass transition temperatures (T). Whereas we detected mAb glycation in the sucrose based formulations, this chemical reaction did not occur in arginine based formulations. Arginine hydrochloride and succinate, especially at high RM levels, could be promising alternatives to sucrose for stabilisation of mAb in lyophilisates.