Residual Moisture Content as Related to Collapse of Freeze‐dried Sugar Matrices

ABSTRACT Amorphous sugars were prepared by freeze‐drying 20% (w/w) aqueous solutions of lactose, sucrose, trehalose and maltose. The dried samples were further dehydrated over P 2 O 5 for 1 wk at 25, 35 or 45°C, and the residual moisture content was determined using oven drying or a thermogravimetric balance. Results indicated a small amount of residual moisture (usually 1–2%) which was not removed by the desiccation treatment for 1 wk at 25°C over P 2 O 5 . The dried samples, heated at a temperature near the published “anhydrous” glass transition temperatures (T g ) exhibited different behavior depending on whether they were heated in open or sealed vials. Structural collapse, a sharply visible shrinkage of the matrix, was found in all samples in sealed vials, while those samples in open vials did not collapse. Thus, removal of the last amount of residual moisture by heating in uncovered vials increased T g , preventing or delaying collapse.