In Situ Characterization of the Microstructural Evolution of Biopharmaceutical Solid-State Formulations with Implications for Protein Stability

Published

January 7, 2019

Author(s)

Stijn H.S. Koshari, Purnendu K. Nayak, Shalini Burra, Isidro E. Zarraga, Karthikan Rajagopal, Yun Liu, Norman J. Wagner, Abraham M. Lenhoff

Abstract

Lyophilized and spray-dried biopharmaceutical formulations are used to provide long-term stability for storage and transport, but questions remain about the molecular structure in these solid formulations and how this structure may be responsible for protein stability. Small-angle neutron scattering with a humidity control environment is used to characterize protein-scale microstructural changes in such solid-state formulations as they are humidified and dried in situ. The findings indicate that irreversible protein aggregates of stressed formulations do not form within the solid-state, but do emerge upon reconstitution of the formulation. After plasticization of the solid-state matrix by exposure to humidity, the formation of reversibly self-associating aggregates can be detected in situ. The characterization of the protein-scale microstructure in these solid-state formulations facilitates further efforts to understand the underlying mechanisms that promote long-term protein stability.

Citation

Molecular Pharmaceutics

Volume

16

Issue

1

Pub Type

Journals

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Keywords

small angle neutron scattering, protein, vapor pressure, formulation

Citation

Koshari, S. , Nayak, P. , Burra, S. , Zarraga, I. , Rajagopal, K. , Liu, Y. , Wagner, N. and Lenhoff, A. (2019), In Situ Characterization of the Microstructural Evolution of Biopharmaceutical Solid-State Formulations with Implications for Protein Stability, Molecular Pharmaceutics, [online], https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=927050 (Accessed October 20, 2025)