Inhibition of Aggregation of Aluminum Hydroxide Adjuvant During Freezing and Drying
Aluminum-salt adjuvants are widely used to increase immunogenicity of recombinant protein vaccines. However, when vaccines formulated with these adjuvants are frozen or lyophilized, losses of efficacy are often reported. This loss of potency is usually attributed to the aggregation of adjuvant parti...
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Published in | Journal of pharmaceutical sciences Vol. 97; no. 6; pp. 2049 - 2061 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken
Elsevier Inc
01.06.2008
Wiley Subscription Services, Inc., A Wiley Company Wiley American Pharmaceutical Association |
Subjects | |
Online Access | Get full text |
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Summary: | Aluminum-salt adjuvants are widely used to increase immunogenicity of recombinant protein vaccines. However, when vaccines formulated with these adjuvants are frozen or lyophilized, losses of efficacy are often reported. This loss of potency is usually attributed to the aggregation of adjuvant particles during processing. In this study, we examine the aggregation behavior of Alhydrogel™, a commercial aluminum hydroxide adjuvant, during freeze-thawing and freeze-drying. By cooling Alhydrogel™ formulations at faster rates or by the addition of sufficient amounts of a glass forming excipient such as trehalose, aggregation of Alhydrogel™, can be prevented or minimized. We propose that freeze-concentration of buffer salts induces modifications in adjuvant surface chemistry and crystallinity, which in turn favor aggregation. These modifications, and the resulting aggregation of Alhydrogel™ particles can be minimized through choice of buffer ions, or kinetically inhibited by rapidly forming a glassy state during freezing. |
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Bibliography: | ArticleID:JPS21143 ark:/67375/WNG-QSKQDX94-2 istex:B38CAD15DE079522EA53E2F2874657B92FC40E80 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0022-3549 1520-6017 |
DOI: | 10.1002/jps.21143 |