EVALUATION OF HEAT-CONDUCTION MICROCALORIMETRY IN PHARMACEUTICAL STABILITY STUDIES .3. CRYSTALLOGRAPHIC CHANGES DUE TO WATER-VAPOR UPTAKE IN ANHYDROUS LACTOSE POWDER

Microcalorimetry at 25.0-degrees-C was used to investigate the incorporation of hydrate water in roller-dried anhydrous lactose that consisted of 31% alpha- and 69% beta-lactose. Differential scanning calorimetry and water vapour uptake measurements were also performed. The samples were stored for various lengths of time in the range 33-94% relative humidity (RH) at ambient temperatures, before measurement. The anhydrous alpha-lactose can accommodate a water molecule to become alpha-lactose monohydrate. Beta-lactose can only exist as the anhydrous form, but it can mutarotate to alpha-lactose and subsequently incorporate water, as shown by others. It was only at the highest humidity investigated (94% RH) that the mutarotation became an extensive process, although it was shown that the mutarotation did proceed at humidities lower than 94% RH and that it started before all the original anhydrous alpha-lactose had been converted to the monohydrate form. With the microcalorimetric technique, it was possible to monitor the incorporation of water after 1 day of storage at 58% RH. Furthermore, after 112 days of storage at 94% RH, it was still possible to detect a process, although the standard DSC instrument could not discriminate a change in the heat of dehydration level. It was concluded that, using microcalorimetry, a sensitive characterization of the incorporation of water in the lactose structure was possible and that microcalorimetry can be useful in solid state stability work.