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

Seifert, Ivonne und Frieß, Wolfgang (2021): The effect of residual moisture on a monoclonal antibody stability in L-arginine based lyophilisates. In: European Journal of Pharmaceutics and Biopharmaceutics, Bd. 158: S. 53-61

Abstract

Amino acids are not only used as buffering agents in lyophilisation, but also exhibit cryoand 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 degrees 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-g). 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Chemie und Pharmazie > Department für Pharmazie - Zentrum für Pharmaforschung
• Themengebiete: 500 Naturwissenschaften und Mathematik > 540 Chemie
• ISSN: 0939-6411
• Sprache: Englisch