Systematic investigation of thermal process parameters on the morphology of spray-freeze-dried powders

Mannitol displayed pronounced process-dependent polymorphism, which is driven by annealing and temperature during sublimation. Lactose and trehalose remained amorphous throughout. Annealing above Tg' promoted viscous flow within the vitrified matrices, producing partial particle fusion and reduced mechanical stability. Variations in recrystallization and Ostwald ripening during annealing systematically altered surface area and pore architecture. This connects annealing to sintering mechanisms, electrical conductivity and mechanical stability of micrometre sized spheres. Across all conditions, SFD consistently yielded spherical, low-density particles, yet the interplay of vitrification and phase transitions generated distinct microstructural outcomes.