Mannitol-sucrose mixtures--versatile formulations for protein lyophilization.

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 degrees C even though the sucrose is amorphous and, by itself, would have required primary drying below -35 degrees C to avoid cake collapse. Formation of an unstable mannitol hydrate is avoided by conducting secondary drying at 40 degrees C or higher.