title: Formulation, lyophilization and solid-state properties of a pegylated protein.
abstract: In this paper the importance of formulation and process parameters on the solid-state properties of a lyophilized, pegylated growth hormone antagonist (pegvisomant) was studied. The degree of solid-state disorder (amorphicity), protein/polyethylene glycol (PEG)/sucrose interactions, and dissolution characteristics of the resultant cakes were examined. Using isothermal microcalorimetry (IMC) and differential scanning calorimetry (DSC), it was shown that in co-lyophilized pegylated protein/sucrose systems there was an interaction between sucrose and pegylated protein molecules. This interaction was evidenced by a decrease in the melting temperature (Tm) and melting enthalpy of PEG as a function of sucrose concentration. It was also shown that the sum of the heat of interaction with water for the individual constituents, lyophilized pegylated protein and lyophilized sucrose, was higher than the heat of interaction for the co-lyophilized system. As the concentration of sucrose was increased, the degree of solid-state disorder increased and the solid dissolved faster. A correlation was found among heat of interaction with water, degree of solid-state disorder, and dissolution time. Pegylation caused a shorter dissolution time, lower moisture content, increased amorphicity, and a more rapid moisture-induced crystallization of sucrose.
authors.affiliation: Product & Process Development, Pfizer Global Manufacturing, Pfizer, SE-112 87 Stockholm, Sweden. mitra.mosharraf@htdcorp.com
authors.forename: Mitra
authors.initials: M
authors.lastname: Mosharraf
authors.forename: Michael
authors.initials: M
authors.lastname: Malmberg
authors.forename: Jonas
authors.initials: J
authors.lastname: Fransson
mesh_terms: D002151:Calorimetry; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D005079:Excipients / Q000737:chemistry*; D005612:Freeze Drying; D019382:Human Growth Hormone / Q000031:analogs & derivatives* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D012995:Solubility; D013395:Sucrose / Q000737:chemistry*; D013816:Thermodynamics; D044366:Transition Temperature; D014961:X-Ray Diffraction
chemical_list: D005079:Excipients; D019382:Human Growth Hormone; D011092:Polyethylene Glycols; D013395:Sucrose; C406545:pegvisomant