The development of DMA for the detection of amorphous content in pharmaceutical powdered materials

The aim of this short study was to develop a novel method of sample presentation that will allow currently available DMA apparatus designed for the testing of self-supporting materials to detect amorphous content in controlled mixtures of amorphous and crystalline powders. The preparation of amorphous lactose was carried out by spraying drying, using a Buchi mini spray drier. Controlled mixtures of amorphous and crystalline lactose were produced to give eight samples ranging between 2% and 75% (w/w) amorphous content. These powdered mixtures were loaded into the DMA using a novel powder-pocket device, which consisted of folded sheet of stainless steel. The pocket was clamped directly into the DMA using a single cantilever configuration, and subjected to oscillating displacement, forcing horizontal shearing of the powder between the two plates of the pocket. Typical experimental parameters were a dynamic displacement of 0.05 mm with a frequency of 1 Hz and a heating rate of 5 degrees C/min, from 25 degrees C to 250 degrees C. Over the glass transition region of amorphous lactose, the storage modulus decreased rapidly and a peak was observed in the tan delta signal, which are typical DMA responses for self-supporting glassy materials over their glass transition region. In both the storage modulus and tan delta signals, contributions from both plasticized and non-plasticized amorphous lactose were demonstrated. Such an observation was caused by the powder pocket restricting the loss of the 2.5% (w/w) water present in the spray-dried lactose within the time scale of the first heating cycle. The tan delta peak for the non-plasticized amorphous lactose showed Arrhenius behaviour as function of oscillation frequency. The relationship between the increase in the tan delta peak with increasing frequency allowed the determination of an activation energy that was comparable to the literature values for similar compounds. The height of the tan delta peak for the non-plasticized material was directly proportional to the amount of amorphous lactose present in the mixtures. The glass transition response was still detectable in mixtures containing as little as 2% (w/w) amorphous content, however the theoretical limit of detection was higher than that determined for the same mixtures using solution calorimetry. The results demonstrate that the novel powder pocket allows the use of conventional DMA instruments for the analysis of pharmaceutical powders, however the technique requires more development to further reduce its theoretical limit of detection. (C) 2005 Elsevier B.V. All rights reserved.