The detection of amorphous material in a nominally crystalline drug using modulated temperature DSC - a case study

Two batches (1 and 2) of an experimental drug (L7) which have shown marked differences in their chemical stability profiles were examined with a view to identifying the presence of small quantities of amorphous material using modulated temperature DSC (MTDSC). The external morphological characterist ics of the two batches were similar although marked differences were seen i n the moisture uptake profiles. MTDSC studies indicated that while no evide nce for a glass transition could be seen for Batch 1, a T-g and accompanyin g relaxation endotherm were observed for Batch 2. Comparison with a glassy form of the drug indicated that the amorphous content was in the region of 5-6% w/w in Batch 2. Dynamic moisture sorption studies indicated that while Batch 2 showed a higher uptake profile than Batch 1, addition of 5% w/w am orphous material to Batch 1 led to the establishment of a very similar prof ile to that seen for Batch 2. It was concluded that Batch 2 contains amorph ous material which is responsible for the greater moisture uptake (and by i mplication poor chemical stability) of this sample and that the glass trans ition of this fraction may be characterised using MTDSC. (C) 1999 Elsevier Science B.V. All rights reserved.