Formulating monoclonal antibodies as powders for reconstitution at high concentration using spray drying: Models and pitfalls.

Autor: Batens M; Drug Delivery and Disposition, KU Leuven, Leuven, Belgium., Massant J; Biological Formulation Development, UCB Pharma, Braine l'Alleud, Belgium., Teodorescu B; Non-Clinical Statistics, UCB Pharma, Braine l'Alleud, Belgium., Van den Mooter G; Drug Delivery and Disposition, KU Leuven, Leuven, Belgium. Electronic address: guy.vandenmooter@kuleuven.be.
Jazyk: angličtina
Zdroj: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V [Eur J Pharm Biopharm] 2018 Jun; Vol. 127, pp. 407-422. Date of Electronic Publication: 2018 Feb 27.
DOI: 10.1016/j.ejpb.2018.02.002
Abstrakt: In anticipation of non-invasive routes capable of delivering adequately high, systemic monoclonal antibody (mAb) concentrations, subcutaneous (SC) injection is arguably the most patient friendly alternative administration route available for this drug class. However, due to the limited volume that can be administered through this route and mAbs' relatively low therapeutic activity, solutions for subcutaneous injection often need to be highly concentrated, making them inherently more prone to potentially detrimental protein (self-) interaction, which is why mAb formulations for SC injection and other highly concentrated mAb solutions are often dried to increase their stability. In this work we investigated spray drying (SD) as a drying technique for formulating mAbs as powders for reconstitution, assessing the influence of SD process parameters, as well as excipients present in the feed solution on both mAb stability and relevant powder characteristics for reconstitution using a model mAb. By employing a design of experiments approach, we were able to provide statistically substantiated evidence for the reconstitution time reducing and stability improving properties of l-arginineHCl, l-histidineHCl, l-lysineHCl and polysorbate 20 when combined with a disaccharide in SD mAb powders for reconstitution. Additionally, the study yielded several statistical models describing process parameter influences on relevant powder and mAb stability characteristics.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: