Solid-State Interaction of Pharmaceutical Cocrystals with Water Vapor

The solid-state properties of an active pharmaceutical ingredient (API) largely determine the effectiveness of drug delivery to the patient. Solid APIs may be exposed to water during manufacturing and storage in an atmosphere containing water vapor. Moisture associated with APIs greatly influences their physicochemical properties such as chemical stability, interactions with excipients, and dissolution. Cocrystal formation with an appropriate coformer can improve solid-state properties of APIs such as chemical stability, photostability, solubility, and bioavailability. Moisture stability of APIs can be enhanced, deteriorated, or remain unchanged by cocrystal formation. Improving solid-state stability, especially against humidity, seems to be one of the most promising applications of cocrystals. Furthermore, to maintain the benefits achieved by cocrystals such as an enhanced dissolution rate, the cocrystals should preserve their structures through formulation, processing, and storage. The current review discusses different aspects of the interactions between pharmaceutical cocrystals and water vapor. First, we provide background information about hygroscopicity, the mechanism of interaction of water molecules with solids, and conventional methods for determining hygroscopicity. Then, the studies comparing the stability of cocrystals and parent APIs are presented. Finally, we discuss the consequences that may occur when a cocrystal interacts with water vapor including dissociation, hydration, polymorphic change, and interaction with excipients.