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

• Published in: The Korean journal of chemical engineering Vol. 35; no. 4; pp. 984 - 993
• Main Authors: Lee, Min-Jeong, Chun, Nan-Hee, Kim, Hyo-Cheol, Kim, Moon-Jip, Kim, Paul, Cho, Min-Yong, Choi, Guang Jin
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.04.2018; Springer Nature B.V; 한국화학공학회
• Subjects: Bioavailability; Biotechnology; Catalysis; Chemical bonds; Chemistry; Chemistry and Materials Science; Crystal structure; Dissolution; Fourier transforms; Hydrogen bonding; Hydroquinone; Industrial Chemistry/Chemical Engineering; Materials Science; Separation Technology; Single crystals; Solubility; Thermodynamics; X-ray diffraction; 화학공학; Hydroquinone; Agomelatine; Solubility; Co-crystal; Resorcinol
• ISSN: 0256-1115; 1975-7220
• DOI: 10.1007/s11814-017-0347-z

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-H∙∙∙O and N-H∙∙∙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.