An investigation into the thermal behaviour of a model drug mixture with amorphous trehalose

M Horvat, E Mestrovic, A Danilovski, D. Q. M. Craig

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The thermal and structural properties of amorphous trehalose mixed with a model drug, paracetamol, have been studied with a view to developing understanding of the thermal events undergone by such binary systems. A physical mixture of paracetamol and spray dried trehalose (1:9 weight ratio) was studied using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), hot stage microscopy (HSM), and variable temperature powder X-ray diffraction (VTPXRD). The presence of the drug resulted in a lower temperature recrystallisation exotherm for the trehalose compared to the disaccharide alone. Evidence is presented for the trehalose recrystallisation being triggered by the melting rather than simply the presence of the paracetamol particles. HSM studies indicated that the trehalose recrystallised around the drug on heating, with the recrystallisation temperature again corresponding to the melting of the drug. VTPXRD indicated that the presence of the drug again lowered the recrystallisation temperature of the trehalose, although the trehalose anhydrate diffraction peaks were discernible at a lower temperature for both the pure trehalose and the mixed systems than was observed for the DSC studies, suggesting that the association between recrystallisation and drug melting was not apparent when using this approach. It is suggested that while the trehalose recrystallisation process is not significantly influenced by the presence of the drug when studied over relatively long time periods such as those used for the VTPXRD studies, the process is triggered by the melting of the paracetamol when short experimental times and scanning conditions are used such as those relevant to DSC studies. These data have implications for the quality control of trehalose products using DSC, the characterisation of the physical structure of the binary systems and the prediction of the corresponding physical stability.
Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalInternational Journal of Pharmaceutical Medicine
Issue number1-2
Publication statusPublished - 27 Apr 2005


  • Amorphous
  • Calorimetry
  • Trehalose
  • X-ray diffraction
  • Spray dried

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