title: Identification and physicochemical characterization of caffeine-citric acid co-crystal polymorphs.
abstract: The purpose of the present study was to identify a new caffeine-citric acid co-crystal (CA-CI) polymorph and characterize three CA-CI polymorphs. The stability order among the three CA-CI polymorphs was also determined. One new and two known CA-CI polymorphs were prepared by the liquid-assisted grinding method or the slurry methods. The three CA-CIs were then identified and characterized by powder X-ray diffraction (PXRD), thermal analysis, IR spectroscopy, Raman spectroscopy, and dynamic vapor sorption (DVS). The stability order of the CA-CIs was determined by the slurry conversion method. Each CA-CI showed distinct PXRD, IR, Raman, and DVS data. The melting points of CA-CIs were 131°C (a new form, Form III), 141°C (Form I), and 160°C (Form II). The order of thermodynamic stability was CA-CI Form II>CA-CI Form I>CA-CI Form III. CA-CI Forms I and II were relatively stable against humidity compared to CA, CI and CA-CI Form III.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan; AsahiKASEI Pharma Corporation, 632-1 Mifuku, Izunokuni-shi, Shizuoka 410-2321, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Mukaida
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan. Electronic address: kiyohiko.sugano@phar.toho-u.ac.jp.
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Sugano
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan.
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Terada
mesh_terms: D002110:Caffeine / Q000737:chemistry*; D019343:Citric Acid / Q000737:chemistry*; D003460:Crystallization; D004355:Drug Stability; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman; D014961:X-Ray Diffraction
chemical_list: D019343:Citric Acid; D002110:Caffeine
keywords: Caffeine; Citric acid; Co-crystal; Humidity; IR; Polymorph; Raman