.g., polymorphs) provides pharmaceutical scientists with an opportunity to select the preferred form of the material to be used in a formulation. This is very useful since critical properties, such as particle morphology and dissolution properties, are frequently different in the different physical forms of a material. The amorphous form of pharmacologically active materials has received considerable attention because, in theory, it represents the most energetic solid state of a material, and should thus provide the biggest advantages in terms of dissolution rate and bioavailability (1). However, the amorphous form also shows various disadvantages, such as lower physical stability compared to crystals.The structure of an amorphous solid is usually described as possessing a crystal--like short-range molecular arrangement, but lacking a long-range order. As illustrated by Fig. 1, the immediate environment of a molecule (m) in an amorphous solid may not differ significantly from that in a crystal (e.g., similar number of and distance to nearest neighbors), but an amorphous solid lacks any long-range transational-orientational symmetry that characterizes a crystal (1). However, this is only true when we are dealing The amorphous form of pharmaceutical materials represents the most energetic solid state of a material. It provides advantages in terms of dissolution rate and bioavailability. This review presents the methods of solid--state amorphization described in literature (supercooling of liquids, milling, lyophilization, spray drying, dehydration of crystalline hydrates), with the emphasis on milling. Furthermore, we describe how amorphous state of pharmaceuticals differ depending on the method of preparation and how these differences can be screened by a variety of spectroscopic (X-ray powder diffraction, solid state nuclear magnetic resonance, atomic pairwise distribution, infrared spectroscopy, terahertz spectroscopy) and calorimetry methods.
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