title: Mannitol-sucrose mixtures--versatile formulations for protein lyophilization.
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 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.
authors.affiliation: Pharmacia Corporation, Research and Development, 4901 Searle Parkway, Skokie, Illinois 60077, USA. robert.e.johnson@pharmacia.com
authors.forename: Robert E
authors.initials: RE
authors.lastname: Johnson
authors.forename: Carol F
authors.initials: CF
authors.lastname: Kirchhoff
authors.forename: Henry T
authors.initials: HT
authors.lastname: Gaud
mesh_terms: D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D004355:Drug Stability; D004926:Escherichia coli; D005612:Freeze Drying / Q000379:methods; D008353:Mannitol / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*; D013395:Sucrose / Q000737:chemistry*; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D011506:Proteins; D008353:Mannitol; D013395:Sucrose