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Aggregation of a Lyophilized Pharmaceutical Protein, Recombinant Human Albumin: Effect of Moisture and Stabilization by Excipients

Bio/Technologyvolume 13pages493496 (1995) | Download Citation

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Abstract

In the presence of water vapor at 37°C, lyophilized recombinant human albumin (rHA) undergoes intermolecular thiol-disulflde interchange, eventually forming high-molecular-weight, water-insoluble aggregates. The relationship between the extent of aggregation and the water content of the lyophilized protein was bell-shaped, with maximum aggregation (over 80% after one day) at approximately 50 g water per 100 g dry protein, corresponding to incubation at 96% relative humidity. Nineteen different excipients were co-lyophilized with rHA to test their ability to inhibit aggregation under these conditions. These compounds included low- and high-molecular-weight sugars, as well as various organic acids (amino, hydroxy, and aliphatic), and the simple inorganic salt sodium chloride. Seven of them afforded complete stabilization of rHA against moisture-induced aggregation. The stabilizing potency of the excipients correlated with their water-sorbing capability, presumably due to increasing the moisture level in the vicinity of rHA.

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Author notes

  1. Alexander M. Klibanov: Corresponding author.

Affiliations

  1. Department of Chemical Engineering, Department of Chemistry, and Biotechnology Process Engineering Center, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139

    • Henry R. Costantino
    • , Robert Langer
    •  & Alexander M. Klibanov

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DOI

https://doi.org/10.1038/nbt0595-493

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