Amorphous pharmaceutical solids: preparation, characterization and stabilization

The importance of amorphous pharmaceutical solids lies in their useful properties, common occurrence, and physicochemical instability relative to corresponding crystals. Some pharmaceuticals and excipients have a tendency to exist as amorphous solids, while others require deliberate prevention of crystallization to enter and remain in the amorphous state. Amorphous solids can be produced by common pharmaceutical processes, including melt quenching, freeze- and spray drying, milling, wet granulation, and drying of solvated crystals. The characterization of amorphous solids reveals their structures. thermodynamic properties, and changes (crystallization and structural relaxation) in single- and multi-component systems. Current research in the stabilization of amorphous solids focuses on: (i) the stabilization of labile substances (e.g., proteins and peptides) during processing and storage using additives, (ii) the prevention of crystallization of the excipients that must remain amorphous for their intended functions, and (iii) the selection of appropriate storage conditions under which amorphous solids are stable. (C) 2001 Elsevier Science B.V. All rights reserved.