Regulating particle morphology during a spray freeze drying ...

INTRODUCTION TO SPRAY FREEZE‐DRYING 13a) b)c) d)Figure 5. Different freezing behaviour of LN 2 ‐supercooled particles due to varyingdroplet sizes: a + b) dilute/concentrated solution with high supercooling – equitable tosmall atomized droplets. High nucleation rates lead to small domains of water andsolute domains in the unfrozen water; c + d) dilute/concentrated solution with lowsupercooling – equitable to larger droplets; Ice particles are represented as whitedomains and solute precipitate as solid dots or grey regions. Pictures taken fromEngstrom et al. [Engstrom et al. 2007b] are originally presented for SFL, but thetransfer to SFD is legitimate.2.2.3 Freeze‐drying stepDuring the water‐removal step in SFD no substantial shrinkage of the frozen dropletsoccurs, contrary to evaporative water loss during SD [Masters 1991]. Lyophilization andwater sublimation start with the primary drying (1°) phase. The chamber pressure isreduced while the shelf temperature is raised to sustain continuous ice sublimation(Figure 6a). The chamber pressure is well below the vapour pressure of ice, so the frozenwater sublimates and deposits as ice onto the cold plates of the condenser (Figure 6b)[Tang et al. 2006]. During the drying process the product temperature (T P ) should notexceed the maximum allowable temperature, which is determined either by the eutectictemperature, T e , for crystalline, or the T g´ for amorphous substances. Alternatively the