Study of curcumin cocrystal formation and properties evaluations

Abstract

Curcumin is the major phytochemical compound derived from Curcuma longa L. It exhibits several pharmacological properties, including homeostatic, antibacterial, antiparasitic, hepatoprotective, antioxidant, and anti-inflammatory activity. The dissolubility and impermeability of curcumin are disadvantageous characteristics that prevent curcumin from being medically utilized as an active medicinal ingredient. Moreover, low absorption rates and prolonged drug dissolution are also characteristics which resulted in reduced curcumin's oral bioavailability. Thus, a variety of pharmacological formulations are designed to increase the solubility and bioavailability of curcumin. To serve the commercial requirement, curcumin have been developed into various forms, such as salt form, derivatives, prodrugs, and cocrystals. Due to its capacity to alter phesicochemical properties such as solubility while retaining the bioactivity of a medicine, cocrystal formation is preferred. In order to enhance the solubility and dissolution of curcumin, this research is aimed to develop cocrystals of curcumin that contain amino acids such as histidine, glutamine, tryptophan, 5-hydroxytryptophan and aspartic acid as coformers. Curcumin cocrystals were synthesized through dry and liquid assisted grinding methods. The cocrystal formation were later verified by FTIR, DSC and PXRD. These curcumin cocrystals' solubility was assessed. It was demonstrated that liquid assisted grinding with ethanol is more favorable method in order to produce curcumin with higher solubility than dry grinding method. The best solubility cocrystal, Cur-Asp, was selected to study the dissolution profile. Curcumin dissolution is boosted by 1.5 times when ground with aspartic acid in both liquid assistance and dry grinding methods.Moreover, through antioxidant assay, cocrystal of curcumin and aspartic acid enhances up to twice antioxidant activity, when compared with pure curcumin. This result obviously proves synergistic effect of cocrystal.