Visualization of the crystallization of lactose from the amorphous state

The physical stability and solid-state recrystallization of spray-dried 'amorphous' lactose particles were visualized using environmentally controlled atomic force microscopy (EC-AFM) and conventional optical microscopy. The morphology and crystalline state were investigated as a function of relative humidity (RH) and were correlated with bulk gravimetric vapor sorption measurements that were run in parallel. The metastable nature of amorphous spray-dried lactose particles was apparent at low RHs (<30% RH). Visualization of the recrystallization transformation of amorphous lactose during moisture uptake at 58 and 75% RH suggested only a proportion of the collapsed particles undergoes nucleation and crystal growth. The irregular surface morphology of the recrystallized particles suggested a secondary nucleation and growth process. Primary nucleation of alpha-lactose monohydrate within the non-recrystallized particles required exposure to elevated RH (94% RH). In relation to bulk measurements of moisture-induced amorphous recrystallization of spray-dried lactose, the results suggest that recrystallization of amorphous lactose, above a critical RH, may be induced by the presence of very low levels of a seed material, which may dramatically reduce the activation energy barrier for nucleation and crystal growth.