Skip to main content

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