Journal
JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 96, Issue 6, Pages 1504-1517Publisher
JOHN WILEY & SONS INC
DOI: 10.1002/jps.20508
Keywords
high concentration protein delivery; monoclonal antibodies; human immunoglobulin G; spray-drying; protein formulation; stabilization; injectables; FTIR; circular dichroism
Ask authors/readers for more resources
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 se administration of mAbs and other low potency protein therapeutics. (C) 2007 Wiley-Liss, Inc.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available