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 ( T m) 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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.