High concentration formulation feasibility of human immunoglubulin G for subcutaneous administration.

The delivery of monoclonal antibodies (mAbs) as subcutaneous (sc) injections hinges on the high dose requirement of these usually low potency molecules. This necessitates their formulation as high concentration solutions or suspensions, which presents a formidable formulation challenge due to the concentration-driven protein aggregation and high solution viscosity generated at these conditions. The objective of this study was to evaluate the feasibility of spray-drying in preparing stable, high concentration formulations of mAbs. A model polyclonal antibody, human immunoglobulin G (IgG) was formulated as dry powder using Nektar's glass stabilization technology. Formulation in sugar glasses stabilized IgG during spray-drying and maintained the protein's secondary structure. Further, in contrast to the bulk material, the glass-stabilized powders successfully reconstituted at 200 mg/mL IgG without loss of the protein monomer. Spectroscopic analysis confirmed that upon high concentration reconstitution, spray-dried glass-stabilized IgG retained both its secondary and tertiary structure. Further, the spray-dried powder reconstituted within a few minutes yielding clear, low viscosity solutions that syringed easily through narrow (28 G) needles. The results of this study suggest that formulation in spray-dried, glass-stabilized powders may enable the development of products suitable for sc administration of mAbs and other low potency protein therapeutics. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96:1504–1517, 2007 [ABSTRACT FROM AUTHOR]