Title: Stable sugar-based protein formulations by supercritical fluid drying
Authors: Jovanovic, Natasa ×
Bouchard, Andranne
Sutter, Marc
Van Speybroeck, Michiel
Hofland, Gerard W
Witkamp, Geert-Jan
Crommelin, Daan J. A
Jiskoot, Wim #
Issue Date: Jan-2008
Publisher: Elsevier science bv
Series Title: International journal of pharmaceutics vol:346 issue:1-2 pages:102-108
Abstract: The aim of this work was to produce stable, sugar-containing protein formulations by supercritical fluid (SCF) drying. Lysozyme solutions with and without added sucrose or trehalose were dried by spraying them in an SCF composed of CO2 and ethanol or CO2 only. The protein-to-sugar ratio was varied between 1:0 and 1: 10 (w/w). Dried formulations were stored at 4 degrees C for three months and analyzed by Karl Fischer titration, scanning electron microscopy, X-ray powder diffraction, differential scanning calorimetry and Fourier transform infrared spectroscopy. Lysozyme stability after reconstitution was determined by an enzymatic activity assay, UVNis spectroscopy, and SDS-PAGE. Smooth, spherical particles of 1-25 mu m size were obtained. All formulations were initially amorphous. Crystallization during storage only occurred with a protein-to-sugar ratio of 1: 10 and could be avoided by performing SCF drying without ethanol. Absence of residual ethanol in dried trehalose formulations increased the class transition temperature up to 120 degrees C. Lysozyme in dried formulations was structurally stable, with exception of the 1:0 and 1: 1 protein-to-sugar ratios, where reversible protein aggregation occurred. The results show that by avoiding ethanol, which up to now has been considered mandatory for efficient drying of aqueous solutions, and by choosing the proper protein-to-sugar ratio, it is possible to obtain stable, sugar-based protein formulations through SCF drying. (C) 2007 Elsevier B.V. All rights reserved.
ISSN: 0378-5173
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Drug Delivery and Disposition
× corresponding author
# (joint) last author

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