Density dependent mechanical properties and structures of a freeze dried biopharmaceutical excipient--sucrose

Knowledge of the mechanical behaviour of freeze dried biopharmaceutical products is essential for designing of products with physical robustness that will not to crack, crumble or collapse during processing or transportation. The compressive mechanical deformation behaviour for freeze-dried sucrose cakes has been experimentally studied from a relative density (ρf/ρs) of 0.01-0.30 using a novel in-vial indentation test. Cakes exhibited more open like structures at lower densities and more closed structures at higher densities with some faces being present at all densities, as confirmed by SEM. The reduced elastic modulus Ef/Es=0.0044(ρf/ρs)(1) for all cake densities, indicating that face stretching was the dominant deformation mode assuming Gibson and Ashby's closed cell model. This linear scaling for the reduced elastic modulus is in line with various theoretical treatments based on tetrakaidecahedral cells and other experimental studies. Consistently, the wall thickness to cell diameter ratio scaled ρf/ρs with a power constant of 1.05. The maximum crushing stress was given by σmax=3800(ρf/ρs)(1.48) which agrees with a strut bending failure stress, assuming Gibson and Ashby's open cell model. Overall, the freeze dried cakes behaved as neither classic closed cell nor open cell materials, with their compressive elastic moduli reflecting a closed cell elastic response whilst their failure stresses reflecting an open cell failure mode. It was concluded that the mechanical response of freeze dried cellular materials depends upon their complex cellular structures and morphologies, and they cannot be rationalised using simple limiting case models of open or closed cell solids.