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Characterization of Protein-Excipient Microheterogeneity in Biopharmaceutical Solid-State Formulations by Confocal Fluorescence Microscopy.
- Source :
-
Molecular pharmaceutics [Mol Pharm] 2017 Feb 06; Vol. 14 (2), pp. 546-553. Date of Electronic Publication: 2017 Jan 17. - Publication Year :
- 2017
-
Abstract
- 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.
Details
- Language :
- English
- ISSN :
- 1543-8392
- Volume :
- 14
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Molecular pharmaceutics
- Publication Type :
- Academic Journal
- Accession number :
- 28094996
- Full Text :
- https://doi.org/10.1021/acs.molpharmaceut.6b00940