Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2485321 | Journal of Pharmaceutical Sciences | 2008 | 14 Pages |
Abstract
To enhance the physical stability of Clostridium difficile toxoids A and B, screening for stabilizing compounds was performed. The screening of 30 GRAS compounds at various concentrations and in several combinations was performed in two parts. First, a high-throughput aggregation assay was used to screen for compounds which delayed or prevented aggregation of toxoids under stress conditions (toxoids at pH 5-5.5 were incubated at 55°C for 55 or 75 min). Compounds which stabilized both proteins were further studied for their ability to delay unfolding under conditions leading to a presumably native-like folded state (pH 6.5). The thermal stability of the toxoids on the surface of Alhydrogel® was monitored with DSC and also showed significant improvement in the presence of certain excipients. This study has generated information concerning the free and adjuvant bound toxoids behavior under a range of conditions (temperature, solutes) that can be used to design pharmaceutical formulations of enhanced physical stability.
Keywords
Related Topics
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Pharmacology, Toxicology and Pharmaceutical Science
Drug Discovery
Authors
Maya S. Salnikova, Sangeeta B. Joshi, J.Howard Rytting, Michel Warny, C.Russell Middaugh,