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Table 2 Methods used to detect and differentiate amorphous state and defects

From: New directions in pharmaceutical amorphous materials and amorphous solid dispersions, a tribute to Professor George Zografi – Proceedings of the June 2016 Land O’Lakes Conference

Method Advantages Disadvantages
XRPD and Rietveld Modeling • Reitveld analysis can be used to understand peak broadening due to size/strain or amorphous content • Requires careful deconvolution of size and strain effects and the assessment of instrumental broadening
DSC • Simple
• Change in heating ramps to delineate differences between in “true” amorphous state and defects
• Variable response from different PSD fractions due to small size
• Recrystallization/annealing depends on the condition of the run and extent of cooling
DEA • Can show typical glassy state signatures – peak loss and beta relaxation
• Response vs. Hz can help delineate the type of transition
• Overlapping signals may be difficult to deconvolute if multiple transitions occur in the same temperature range
SSNMR • Molecular level picture
• Relaxation time maps can help differentiation
• Long acquisition times in only 13C are available
• Labeling may be required to deconvolute origins of transitions at the molecular level
• Indirect indication of structure through relaxation time measurements
Pair Distribution Function analysis • Molecular level picture of the phase
• More sensitive to local structure/order
• Careful analysis of data is required
• Molecular models may be needed for getting a complete picture
  1. DEA Dielectric analysis
  2. SSNMR Solid state NMR