Effect of moisture sorption on tabletting characteristics of spray dried (15% amorphous) lactose.

Spray dried (15% amorphous) lactose absorbs moisture when exposed to humidity. At 57% relative humidity (RH), the moisture uptake was 1.5%. It is suggested that the moisture is preferentially taken up in the amorphous regions, thereby increasing the actual moisture content in the amorphous parts up to 10%. The moisture uptake reduced the glass transition temperature below the operating temperature and thereby transformed the amorphous regions from a glassy to a rubbery state, setting up conditions for crystallisation of the lactose. Compaction of dry spray dried lactose led to a relatively low initial tablet strength. However, when pre-exposed to 57% RH for a short time period (2 to 4 hours) before compaction, the initial tablet strength increased markedly. This was due to moisture uptake which resulted in a higher molecular mobility of the amorphous spray dried lactose, and to an increase in plastic flow. Post compaction storage of tablets containing amorphous regions of spray dried lactose at 57% RH resulted in an increased tablet strength after 4 hours due to crystallisation. Spray dried lactose exposed to 57% RH for more than 6 hours before compaction led to the lowest initial tablet strength. Crystallisation of the amorphous regions of the spray dried lactose occurred before tabletting. No increase in tablet strength was noted on post compaction storage for these tablets.