Pharmaceutical solvates, hydrates and amorphous forms: A special emphasis on cocrystals

Abstract

Active pharmaceutical ingredients (APIs) may exist in various solid forms, which can lead to differences in the intermolecular interactions, affecting the internal energy and enthalpy, and the degree of disorder, affecting the entropy. Differences in solid forms often lead to differences in thermodynamic parameters and physicochemical properties for example solubility, dissolution rate, stability and mechanical properties of APIs and excipients. Hence, solid forms of APIs play a vital role in drug discovery and development in the context of optimization of bioavailability, filing intellectual property rights and developing suitable manufacturing methods. In this review, the fundamental characteristics and trends observed for pharmaceutical hydrates, solvates and amorphous forms are presented, with special emphasis, due to their relative abundance, on pharmaceutical hydrates with single and two-component (i.e. cocrystal) host molecules.

Keywords: Amorphous form; Cocrystal; Hydrated cocrystal; Hydrates; Solid dispersion; Solid state characterization; Solvated cocrystal; Solvates; Tendency for hydrate formation; Water cluster.