Abstract

Poor aqueous solubility of a drug substance can often be attributed to strong intermolecular forces within its crystal lattice, which, in turn, prevent molecules from escaping in solution. Through the use of solid-state chemistry, it is possible to modify the crystal structure in such a way that mitigates intermolecular forces, thus improving aqueous solubility and increasing rates of dissolution. Solid-state techniques utilized for solubility enhancement include the formation of salts, polymorphic or amorphous forms, and cocrystals. Each technique has specific advantages and, in some cases, disadvantages that may prevent its successful use. The purpose of this chapter is to describe each of the methods, allowing the reader to gain an understanding of solid-state modifications available for solubility enhancement.