Effects of moisture sorption and temperature on amorphous spray dried lactose

An isothermal microcalorimetry technique based on the ability of amorphous spray dried lactose to absorb large amounts of water was developed in order to follow the transition of the metastable amorphous form to the more stable crystalline form. A sharp response was measured, indicating a rapid process with the whole sample crystallising simultaneously. Crystallisation was monitored by weight changes due to water uptake and subsequent loss after crystallisation. DSC and TGA data revealed that the crystallised form contained a mixture of beta, alpha-anhydrous and alpha monohydrate forms. Physical mixtures of amorphous and crystalline lactose were used to investigate the lower detection limit of these two techniques for amorphous material. These were 0.3% for microcalorimetry and ca 0.1% for the gravimetric method. The water sorption behaviour of the amorphous lactose and water mobility below and close to the glass transition temperature (Tg) was investigated. Exposure of the spray dried lactose to 50%RH for varying lengths of time resulted in structural collapse of the amorphous sample to different degrees. The collapsed material did not crystallise instantaneously and water desorption from this structure was shown to be slow. DSC and TGA studies revealed that during heating the collapsed lactose crystallised at around 70°C compared to the uncollapsed material, which crystallised at around 180°C. Drying at 0%RH and 25°C also resulted in eventual crystallisation of the collapsed material. DSC studies on compressed samples revealed a reduced crystallisation temperature of around 120°C. With increased temperature crystallisation occurred more rapidly and required a lower water content. Moisture uptake and crystallisation in bulk samples (up to 100g) of two partially amorphous lactose materials, Zeparox and Pharmatose, was also investigated. These samples crystallised gradually, on exposure to 75%RH, as water was passed down through the powder bed. A net negative weight change indicated that the spray dried lactose did not form a complete hydrate on crystallising.