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 characteristics of the two batches were similar although marked differences were seen in the moisture uptake profiles. MTDSC studies indicated that while no evidence for a glass transition could be seen for Batch 1, a T(g) and accompanying 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 amorphous material to Batch 1 led to the establishment of a very similar profile to that seen for Batch 2. It was concluded that Batch 2 contains amorphous material which is responsible for the greater moisture uptake (and by implication poor chemical stability) of this sample and that the glass transition of this fraction may be characterised using MTDSC.
Saklatvala
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R
Development Laboratories, Merck, Sharp and Dohme, Hertford Rd., Hoddesdon, UK.
Royall
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PG
Craig
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DQ
D000327:Adsorption; D002152:Calorimetry, Differential Scanning / Q000379:methods*; D003460:Crystallization; D008855:Microscopy, Electron, Scanning; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D014867:Water / Q000032:analysis; D014961:X-Ray Diffraction
D004364:Pharmaceutical Preparations; D014867:Water