EVALUATION OF HEAT-CONDUCTION MICROCALORIMETRY IN PHARMACEUTICAL STABILITY STUDIES .6. CONTINUOUS MONITORING OF THE INTERACTION OF WATER-VAPOR WITH POWDERS AND POWDER MIXTURES AT VARIOUS RELATIVE HUMIDITIES

The water vapour uptake by microcrystalline cellulose (MCC) and a powder mixture composed of roller-dried beta-lactose (which consisted of 22% anhydrous alpha-lactose, 9% alpha-lactose monohydrate and 69% anhydrous beta-lactose) and MCC was continuously monitored at 100% relative humidity (RH) using isothermal heat-conduction microcalorimetry at 25.0-degrees-C. For the powder mixture, three phases of water vapour uptake were distinguished, i.e., firstly the absorption of water by MCC, secondly the incorporation of water of hydration into the original anhydrous alpha-lactose fraction and finally incorporation of water into anhydrous alpha-lactose that had been obtained by mutarotation from the beta-lactose fraction. The combination of the cumulative heat values for the single materials were comparable to the mixture of the two, i.e., the processes were additive and the powders did not interact. However, for mixtures that had been stored for a long time at 94% RH and later monitored at 100% RH, an unknown process was indicated by the heat flow curve. Continuous measurements were also performed at 75, 81 and 94% RH. The interpretation of the heat flow curves for the mixtures was not as straightforward at the lowest humidities investigated as at 100% RH, but the water vapour was absorbed by the MCC first, in these cases also. At both 100 and 94% RH, the incorporation rate of water in roller-dried beta-lactose alone was shown to be more rapid than in the mixture with MCC. At 75 and 81% RH, the difference in the extent of the incorporation process was small after 14 days exposure.