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A Package of Established Analytical Tools to Investigate the Solid-State Alteration of Lipid-Based Excipients
Published on: August 9, 2022
Formulation, lyophilization and solid-state properties of a pegylated protein
Mitra Mosharraf1, Michael Malmberg, Jonas Fransson
1Product & Process Development, Pfizer Global Manufacturing, Pfizer, SE-112 87 Stockholm, Sweden. mitra.mosharraf@htdcorp.com
International Journal of Pharmaceutics
|January 9, 2007
Summary
Formulation affects lyophilized pegylated growth hormone antagonist (pegvisomant) properties. Higher sucrose concentrations increase disorder and dissolution rates, while pegylation enhances these effects.
Area of Science:
- Pharmaceutical Sciences
- Biophysical Chemistry
- Materials Science
Background:
- Lyophilization is crucial for stabilizing therapeutic proteins.
- Pegylated proteins offer extended circulation times.
- Understanding solid-state properties is key for drug product performance.
Purpose of the Study:
- Investigate formulation and process impacts on lyophilized pegvisomant.
- Characterize solid-state disorder, molecular interactions, and dissolution.
- Establish correlations between physical properties and formulation variables.
Main Methods:
- Isothermal microcalorimetry (IMC) for thermal analysis.
- Differential scanning calorimetry (DSC) for phase transitions.
- Analysis of protein/polyethylene glycol (PEG)/sucrose interactions.
- Assessment of cake dissolution characteristics.
Main Results:
- Evidence of interaction between sucrose and pegylated protein, indicated by decreased PEG melting temperature and enthalpy.
- Increased solid-state disorder (amorphicity) with higher sucrose concentrations.
- Faster dissolution rates correlated with increased amorphicity and sucrose concentration.
- Pegylation led to shorter dissolution times, lower moisture, increased amorphicity, and faster sucrose crystallization.
Conclusions:
- Formulation composition significantly influences the solid-state properties of lyophilized pegvisomant.
- Sucrose concentration is a critical parameter affecting protein/excipient interactions and dissolution.
- Pegylation impacts physical stability and dissolution behavior, requiring careful formulation design.
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