Curcumin, a Biological Wonder Molecule: A Crystal Engineering Point of View

Curcumin is a principal active ingredient of turmeric, extracted from the Curcuma longa plant. The presence of several curcuminoids (e.g., curcumin, demethoxycurcumin, bisdemethoxycurcumin, and cyclocurcumin) with extended pi-pi conjugation makes the Indian spice turmeric a bright yellow color. Curcumin can modulate various cellular targets and exhibits preventive and clinical efficacy against a wide variety of diseases such as inflammatory, proliferative, and angiogenic diseases, Alzheimer's disease, malaria, cancer, HIV, etc. Curcumin has been widely exploited by several branches of research scientists to study the chemistry behind its biological and chemical significance. However, application of curcumin is limited as medicine due to its poor aqueous solubility and bioavailability. While there are recent reports on curcumin on solubility/bioavailability improvement using excipients/additives, there has been little discussion from the viewpoint of crystal engineering. There is a need for understanding of the solid phases of curcumin to tailor physicochemical properties as they are alternative preformulations with prominent applications in pharma. Hence, in this review, we will focus on several crystalline solid forms such as polymorphs, cocrystals, eutectics, and noncrystalline solid forms like amorphous phases and coamorphous solid forms of curcumin reported in the literature/patent to date. In addition, we will briefly discuss metal complexes of curcumin and their application in drug development in combating modern lifestyle related diseases like cancer, Alzheimer's, etc.