Methods of amorphization and investigation of the amorphous state

Abstract

.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.

Variability in bioavailability of small molecular tyrosine kinase inhibitors

“…The particular crystal structure chosen for the pharmaceutical product offers the best combination of stability and solubility. Besides crystal structures, solid compounds can arrange themselves in a more loosely-ordered amorphous state [80]. The advantage of the amorphous form is the higher apparent solubility, owing to the high levels of supersaturation in aqueous media [81].…”

Reentrant phase transformation from crystalline ikaite to amorphous calcium carbonate

“…A typical example is mechanical grinding of crystalline materials, which may lead to amorphous materials via generation of localized heating followed by quenching, via an increase in disorder or massive creation of defects. 5,6 It can also be caused by hydrogenation of intermetallics where hydrogen atoms in crystalline phases are less energetically favourable. 7 In addition, dehydration of crystalline hydrates has been demonstrated as a route to the amorphous state of several organic solids 5 or copper sulphate pentahydrate.…”

“…5,6 It can also be caused by hydrogenation of intermetallics where hydrogen atoms in crystalline phases are less energetically favourable. 7 In addition, dehydration of crystalline hydrates has been demonstrated as a route to the amorphous state of several organic solids 5 or copper sulphate pentahydrate. 8 Finally, crystalline coordination networks or highly porous metal-organic frameworks become amorphous upon losing constitutional solvent molecules.…”

Co-Amorphous Combination of Nateglinide-Metformin Hydrochloride for Dissolution Enhancement

“…From the manufacturing viewpoint, ball milling is a green technology and is superior to solvent approaches (28). In this study, NT and MT are ball milled in varying ratios in order to check the feasibility of co-amorphization.…”