Agomelatine co-crystals with resorcinol and hydroquinone: Preparation and characterization

Abstract

We prepared and characterized co-crystals of the antidepressant drug agomelatine with pharmaceutically acceptable coformers for enhanced solubility. A novel agomelatine-resorcinol (AGO-RES, 2 : 1) co-crystal was synthesized and its crystal structure was confirmed via single crystal X-ray diffraction. The AGO-RES co-crystal structure was created through the O-Ha (TM) a (TM) a (TM) O and N-Ha (TM) a (TM) a (TM) O hydrogen bonding between the phenolic OH of RES and the amide group of AGO. The chemical structure of two AGO co-crystals was characterized by FT-IR and Raman spectroscopies, whereas the solution behavior was determined by the intrinsic dissolution rate. When tested in water, both AGORES and AGO-HYQ form-I co-crystals showed higher apparent solubility than pure AGO. But the resulting AGO solution in a supersaturated state partially precipitated into specific crystal forms of AGO. As anticipated, the intrinsic dissolution rate of AGO was substantially enhanced by the co-crystal forms, which signifies that the bioavailability of AGO can be increased via co-crystal formulation approach.