Quantification of amorphous content in mixed systems: amorphous trehalose with lactose

There has been a lot of interest in quantification of the amorphous content of materials, especially when the amorphous content is a small percentage of the total mass. Whilst there has been success in studies on single materials, there has been little work showing how quantification of the amorphous content of one material can be undertaken in the presence of another. In this work isothermal microcalorimetry was used to measure the content of amorphous trehalose following mixing with crystalline lactose. Gravimetric water sorption studies revealed that trehalose did not form a complete dihydrate when exposed to 75% RH, presumably due to the rapid crystallisation of the outer regions of the particles. At 53% RH, the gravimetric studies showed dihydrate formation. The calorimetry data revealed that the crystallisation response was directly related to the mass of amorphous material in the mixture and was not affected by the mass of non-crystallising sample. It was shown that as long as there was a minimum mass of amorphous material (in this case 4 mg), it was possible to measure a crystallisation response with sufficient accuracy to allow quantification. Lower masses of amorphous content allowed detection, but less accurate quantification, as the response was superimposed on the initial calorimetric heat flow response. It was also found that the response at 53% RH in the TAM was less accurate due to the low peak height and long duration (compared to that seen at 75% RH). It can be concluded that the TAM method is well suited to both detection and quantification of amorphous content when there is one amorphous sample mixed with another (and thus presumably more than one) non-crystallising material. (C) 2004 Elsevier B.V. All rights reserved.