Aggregation of a lyophilized pharmaceutical protein, recombinant human albumin: effect of moisture and stabilization by excipients

Biotechnology (N Y). 1995 May;13(5):493-6. doi: 10.1038/nbt0595-493.

Abstract

In the presence of water vapor at 37 degrees C, lyophilized recombinant human albumin (rHA) undergoes intermolecular thiol-disulfide 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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Albumins / chemistry*
  • Chemistry, Pharmaceutical*
  • Drug Stability
  • Excipients
  • Freeze Drying
  • Humans
  • Protein Conformation*
  • Recombinant Proteins / chemistry
  • Solubility
  • Water / chemistry

Substances

  • Albumins
  • Excipients
  • Recombinant Proteins
  • Water