Advanced methodologies for cocrystal synthesis.

Pharmaceutical cocrystals are multicomponent systems composed of two or more molecules and held together by H-bonding. Currently, cocrystals provide exciting opportunities in the pharmaceutical industry for the development and manufacturing of new medicines by improving poor physical properties of Active Pharmaceutical Ingredients (APIs) such as processability, solubility, stability and bioavailability. According to the recent reclassification, cocrystals are considered as drug polymorph rather a new API which has a significant impact on drug development, regulatory submissions and intellectual property protection. This review summarizes recent trends and advances in synthesis, manufacturing and scale - up of cocrystals. The operational principles of several cocrystals manufacturing technologies are discussed including their advantages and disadvantages in terms of crystal quality, purity stability, throughput and limitations in large scale production.