Different solid forms of identical drug may have diverse physicochemical properties, therapeutic/toxicological effects and formulation profiles. Compared to solvates and salts which are limited to small numbers of nontoxic solvents and ionizable drugs, cocrystals represent the very promising designable solid forms of active pharmaceutical ingredients, due to their extensive species and wide application scope. In this article, progress on pharmaceutical cocrystals, including the formation principles, cocrystal design, physicochemical properties and preparation techniques, is addressed. Cocrystals have great potentials in pharmaceutical sciences.
Contents
1 Introduction
2 Principle of cocrystal formation
3 Design of cocrystals
3.1 Interaction-based design
3.2 Molecular properties-based design
3.3 Host molecule-based design
4 Properties of cocrystals
4.1 Melting point
4.2 Hygroscopicity
4.3 Stability
4.4 Solubility and dissolution
4.5 Bioavailability
4.6 Release
4.7 Mechanical properties
4.8 Phase diagram
4.9 Application in separation and purification
5 Preparation of cocrystals
5.1 Crystallization from solvent
5.2 Solid state grinding
5.3 Sonication
5.4 Supercritical fluid technology
6 Outlook