An industrial perspective on co-crystals: Screening, identification and development of the less utilised solid form in drug discovery and development

Abstract

Active pharmaceutical ingredients are commonly marketed as a solid form due to ease of transport, storage and administration. In the design of a drug formulation, the selection of the solid form is incredibly important and is traditionally based on what polymorphs, hydrates or salts are available for that compound. Co-crystals, another potential solid form available, are currently not as readily considered as a viable solid form for the development process. Even though co-crystals are gaining an ever-increasing level of interest within the pharmaceutical community, their acceptance and application is still not as standard as other solid forms such as the ubiquitous pharmaceutical salt and stabilised amorphous formulations. Presented in this chapter is information that would allow for a co-crystal screen to be planned and conducted as well as scaled up using solution and mechanochemistry based methods commonly employed in both the literature and industry. Also presented are methods for identifying the formation of a co-crystal using a variety of analytical techniques as well as the importance of confirming the formation of co-crystals from a legal perspective and demonstrating the legal precedent by looking at co-crystalline products already on the market. The benefits of co-crystals have been well established, and presented in this chapter are a selection of examples which best exemplify their potential. The goal of this chapter is to increase the understanding of co-crystals and how they may be successfully exploited in early stage development.

Keywords: Bioavailability; Co-crystals; Crystallisation; Formulation; Mechanochemistry; Phase diagrams; SCXRD; Solubility.