Chemistry Reference
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solid-state instabilities [11]. In conclusion, given that different methods used to form
amorphous solids can lead to glasses with somewhat different properties, it is important
to recognize that the various pharmaceutical processes used to produce robust amorphous
drug products of high quality and performance must be under very careful control with regard
to time, temperature, and other process conditions.
1.3 STRUCTURE OF AMORPHOUS SOLIDS
The structural arrangement of molecules in crystals, as determined by intermolecular
interactions and molecular size and shape, can be described in terms of a speci
c local
structure re
ected by the geometric arrangement of molecules within the unit cell, and
the long-range symmetrical three-dimensional extension of the repeating unit cells. The
same molecule in the crystalline state may be able to form in different unit cells, and,
therefore, to exist in distinctly different polymorphic forms. Single-crystal X-ray
diffraction techniques are used to determine the arrangement of molecules in the unit
cell, while, as shown in Figure 1.6, powder X- ray diffraction measurements (PXRD)
reveal distinct diffraction peaks at characteristic scattering angles that represent the
various planes of long-range symmetry within the crystal and can be used to identify the
crystal form. Liquids and supercooled liquids, on the other hand, having lost the long-
range three-dimensional order of the crystal will exhibit PXRD patterns that are devoid of
these distinct peaks, rather than exhibiting a broad halo of X-ray intensity, as seen in
Figure 1.6. From extensive studies of liquids and supercooled liquids, it has been
Figure 1.6.
Typical powder X-ray diffraction patterns for crystalline and amorphous forms.
