Co-crystallization: a green approach for the solubility enhancement of poorly soluble drugs

Abstract

Recently, the co-crystallization of pharmaceutical drugs is gaining consideration because it is an environmentally friendly and potentially effective technique to improve the solubility and bioavailability of poorly soluble drugs without altering the chemical identity or reducing the biological activity or therapeutic effect of the active pharmaceutical ingredient (API). The co-crystallization process in the pharmaceutical industry is still not fully utilized owing to the limited methods for large-scale production. However, it is a very convenient, appropriate, and green technique in the field of drug development research as only a few synthetic steps are involved with the minimal or no use of solvents. Herein, the selection criteria or the factors that affect the selection of coformers in this process are discussed. In addition, the different stages of co-crystal manufacturing, from the screening phase to industrial production, are identified and the use of continuous and scalable methods in co-crystal production as well as the implementation of quality-by-design and process analytical technology concepts are addressed. The potential pharmaceutical applications, like the enhancement in drug solubility, and the drug dissolution rate, which consequently leads to improved bioavailability and therapeutic efficacy, are also highlighted. This study briefly reviews different strategies for enhancing the solubility of poorly soluble drugs with a special emphasis on co-crystal formation, including solvent-based and solvent-free methods of production.