Pharmaceutical Cocrystals—A Review

Abstract

The design and synthesis of pharmaceutical cocrystals have received great interest in the recent years. Cocrystallization of drug substances offers a tremendous opportunity for the development of new drug products with superior physical and pharmacological properties such as solubility, stability, hydroscopicity, dissolution rates and bioavailability. This short review summarizes this highly topical field, covering why the topic is of interest in pharmaceutical formulation, the definitions and practical scope of cocrystals, cocrystal preparation and characterization, a comparison of different (traditional and novel) methods for cocrystal formation and the implications for regulatory control and intellectual property protection. Traditionally, cocrystals can be prepared by solvent evaporation method, grinding, and slurry method, but every method has its limitations for certain conditions. The current trend for cocrystal formation uses sophisticated methods such as the hot melt extrusion method, spray-drying method, supercritical fluid technology and the newest method: laser irradiation. The purpose of the development of a new method is not only to overcome the limitation of traditional cocrystallization methods, but also to generate simpler steps and a continuous process for the production of the cocrystal product. This article provides a brief explanation of each method that can be used to generate pharmaceutical cocrystals as well as evaluation of cocrystals. This article also covers how the developing field of cocrystallization may impact the pharmaceutical intellectual property landscape.

Keywords

• pharmaceutical cocrystals (PC)
• cocrystallization
• active pharmaceutical ingredient (API)
• generally recognized as safe (GRAS)
• cocrystal former (CF)
• novel methods