THE INFLUENCE OF ADDITIVES ON THE RECRYSTALLIZATION OF AMORPHOUS SPRAY-DRIED LACTOSE

Amorphous material in crystals can constitute reactive 'hot spots', wh ich can be centres for chemical degradation or physical transitions, l eading to product instability. Problems have been encountered in study ing small amounts of amorphous content for powdered systems, due to po or sensitivity of the majority of techniques. Isothermal microcalorime try has been shown to have good resolution for cases where the amorpho us content of the powder can be made to recrystallise in the instrumen t. In this study amorphous lactose has been investigated, being recrys tallised by exposure to air at 75% RH. The lactose has been studied in two layers separated by varying amounts of glass beads (inert carrier ), magnesium stearate (hydrophobic excipient), or microcrystalline cel lulose (hygroscopic excipient). Significant differences were observed in the time needed to cause recrystallisation when amorphous material was separated by these different additives. Glass beads had only a sma ll effect, but magnesium stearate caused an increased lag time prior t o the recrystallisation event. In both these cases the lactose all rec rystallised at one time, even though it was divided into two physicall y separated regions. A layer of microcrystalline cellulose between two layers of amorphous lactose resulted in a long lag time prior to recr ystallisation, as it removed considerable amounts of water vapour from the atmosphere, thus preventing saturation of the lactose. By varying the weight of amorphous lactose in the upper and lower layers, and co mparing data with the results obtained for homogeneous mixtures, it wa s possible to postulate a mechanism for the cooperative recrystallisat ion process. In essence, the water vapour is absorbed into the upper l ayers of the sample, and then transferred away yielding a concentratio n gradient through the entire sample in the cell. As the water content gradually increases in the lower layers, the rate of water absorption can become more rapid than the rate at which water is transferred awa y from the surface. After this time the surface saturates, starts to r ecrystallise thus liberating a great excess of water vapour, which is sufficient to cause the lower layers of powder to become saturated and also to recrystallise.