Evaluating the impact of annealing and radiative cooling on a PEGylated peptide formulation subjected to continuous spin-freeze-drying

Annealing is commonly used in traditional lyophilization processes to crystallize solutes, improve drying efficiency and reduce cake heterogeneity, yet its integration into continuous spin-freeze-drying has not yet been reported. This study investigates the effects of incorporating annealing into continuous spin-freeze-drying processes with a model peptide formulation. Contrary to expectations, annealing resulted in a compromised cake structure, including skin formation and extended drying times. In contrast, when annealing was not applied, an intact cake structure was observed. This was likely due to product temperatures exceeding the formulation's collapse threshold during primary drying. Further analysis suggested that specific formulation components contributed to these adverse outcomes, potentially due to phase separation. To mitigate such effects, a radiative cooling technology was implemented for continuous spin-freeze-drying to achieve precise temperature control and minimize background radiation during drying. While radiative cooling effectively maintained product temperatures below the collapse point, samples still displayed poor cake appearance and longer drying times when annealed compared to their non-annealed counterparts. Despite these issues, the peptide remained stable under all conditions. These findings highlight the necessity for careful process optimization when considering annealing and underscore the potential benefits of radiative cooling in improving product quality under certain conditions.