The aim of this study was to investigate if mechanistically different controlled ice nucleation techniques in freeze-drying are comparable to each other with respect to drying process performance and product quality attributes. Therefore, we studied 3 different model formulations including amorphous (sucrose, trehalose) and semi-crystalline (mannitol:sucrose 4:1) solids containing a monoclonal antibody IgG1 (5 g/L) processed either by application of ice fog or depressurization technique setting an ice nucleation temperature of -5°C. Subsequently, the same freeze-drying protocol on identical machinery was applied. The results showed that the techniques are comparable with respect to the thermal history of product temperature sensors and primary drying time, solid state- and protein-related product quality attributes. All analytics comprising Karl Fischer titration, X-ray powder diffraction and Brunauer-Emmet-Teller as well as high-performance size exclusion chromatography, turbidity and subvisible particle counting using flow-imaging microscopy exhibited similarity and comparability among the controlled nucleation protocols.
Keywords: X-ray powder diffraction; amorphism; drying; excipients; freeze-drying; lyophilization; monoclonal antibody; protein; solid-state.
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