Mannitol–sucrose mixtures—versatile formulations for protein lyophilization

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Abstract

Mixtures of sucrose (a lyoprotectant) and mannitol (a bulking agent) have been investigated as excipients for the lyophilization of proteins. Four proteins under development have been successfully lyophilized in a formulation of 4% mannitol and 1% sucrose using a lyophilization cycle that produces a cake of crystalline mannitol and amorphous sucrose. The crystalline mannitol allows primary drying to be performed with a product temperature of −10°C even though the sucrose is amorphous and, by itself, would have required primary drying below −35°C to avoid cake collapse. Formation of an unstable mannitol hydrate is avoided by conducting secondary drying at 40°C or higher. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91: 914–922, 2002

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