Surface adsorption of recombinant human interferon-? in lyophilized and spray-lyophilized formulations

Surface adsorption of recombinant human interferon-? in lyophilized and spray-lyophilized formulations
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Author(s)
Serena D. Webb, Stephen L. Golledge, Jeffrey L. Cleland, John F. Carpenter, Theodore W. Randolph,
Journal
J. Pharm. Sci.
Vol. 91, No. 6, pages 1474-1487 (2002)
DOI: 10.1002/jps.10135
ISSN
0022-3549
Publisher
Wiley-Liss, Inc. and the American Pharmaceutical Association
Abstract
Recombinant human interferon-? (rhIFN-?) was lyophilized or spray-lyophilized in 9.5% trehalose, ? 0.12% polysorbate 20 in 10 mM potassium phosphate, pH 7.5. We measured recovery of soluble protein after spraying, freeze-thawing, and drying and reconstitution. Infrared spectroscopy showed rhIFN-? secondary structure to be native-like in all dried powders. Powders were characterized using electron spectroscopy for chemical analysis, time-of-flight secondary ion mass spectroscopy, X-ray diffraction, and gas adsorption isotherms. rhIFN-? adsorbed at air/liquid interfaces during spraying, and to ice/liquid interfaces during lyophilization. The concentration of rhIFN-? at ice/liquid interfaces was approximately one-fourth that adsorbed at air/liquid interfaces. Addition of 0.12% polysorbate 20 reduced the concentration of rhIFN-? at both interfaces. Time-of-flight secondary ion mass spectroscopy detected polysorbate 20 on surfaces of lyophilized powders. Lyophilized samples dried more slowly but reconstituted more quickly than spray-lyophilized samples. rhIFN-? aggregated after nebulization, but aggregation decreased in 0.12% polysorbate 20. Addition of 0.12% polysorbate 20 reduced protein surface adsorption and decreased but did not completely prevent aggregation. Insignificant aggregation occurred after exposure to ice/liquid interfaces, but subsequent drying and reconstitution caused aggregation. The majority of the aggregation is due to adsorption at air-liquid and solid-air interfaces formed during spray-lyophilization or lyophilization. ? 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:1474-1487, 2002
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