Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2487770 | Journal of Pharmaceutical Sciences | 2007 | 14 Pages |
Abstract
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 concentrationâdriven protein aggregation and high solution viscosity generated at these conditions. The objective of this study was to evaluate the feasibility of sprayâdrying 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 sprayâdrying and maintained the protein's secondary structure. Further, in contrast to the bulk material, the glassâstabilized powders successfully reconstituted at 200Â mg/mL IgG without loss of the protein monomer. Spectroscopic analysis confirmed that upon high concentration reconstitution, sprayâdried glassâstabilized IgG retained both its secondary and tertiary structure. Further, the sprayâdried powder reconstituted within a few minutes yielding clear, low viscosity solutions that syringed easily through narrow (28Â G) needles. The results of this study suggest that formulation in sprayâdried, glassâstabilized powders may enable the development of products suitable for sc administration of mAbs and other low potency protein therapeutics.
Keywords
USP, united states pharmacopoeiaspray‐dryingATR, Attenuated total reflectanceFTIR, Fourier transform infraredOD, optical densityPTH, parathyroid hormoneRH, relative humiditySC, subcutaneousSEC, Size Exclusion ChromatographyBSA, bovine serum albuminHuman immunoglobulin GIgG, immunoglobulin GInjectablescircular dichroismCD, circular dichroismFDA, Food and Drug AdministrationFTIRProtein formulationmAb, Monoclonal antibodyMonoclonal antibodiesStabilizationHPLC, high performance liquid chromatography
Related Topics
Health Sciences
Pharmacology, Toxicology and Pharmaceutical Science
Drug Discovery
Authors
Bhas Dani, Robert Platz, Stelios T. Tzannis,