1 research outputs found
Characterization of Protein–Excipient Microheterogeneity in Biopharmaceutical Solid-State Formulations by Confocal Fluorescence Microscopy
Protein-stabilizer
microheterogeneity is believed to influence
long-term protein stability in solid-state biopharmaceutical formulations
and its characterization is therefore essential for the rational design
of stable formulations. However, the spatial distribution of the protein
and the stabilizer in a solid-state formulation is, in general, difficult
to characterize because of the lack of a functional, simple, and reliable
characterization technique. We demonstrate the use of confocal fluorescence
microscopy with fluorescently labeled monoclonal antibodies (mAbs)
and antibody fragments (Fabs) to directly visualize three-dimensional
particle morphologies and protein distributions in dried biopharmaceutical
formulations, without restrictions on processing conditions or the
need for extensive data analysis. While industrially relevant lyophilization
procedures of a model IgG1 mAb generally lead to uniform protein–excipient
distribution, the method shows that specific spray-drying conditions
lead to distinct protein–excipient segregation. Therefore,
this method can enable more definitive optimization of formulation
conditions than has previously been possible