title: Kinetics of co-crystal formation with caffeine and citric acid via liquid-assisted grinding analyzed using the distinct element method.
abstract: The kinetics of co-crystal formation of caffeine (CF) with citric acid (CTA) was evaluated. Ball milling of CF and CTA in molar ratios of 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, and 1:4 was performed by the liquid-assisted grinding (LAG) method. The samples were characterized by powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). Two types of co-crystals (co-crystal-1, a 1:1 CF-CTA co-crystal; and co-crystal-2, a new co-crystal form) were obtained. The kinetic characteristics of this new co-crystal formation were assessed by calculating the ball impact energy and force using the distinct element method (DEM) simulations. The results indicated that co-crystal-2 creation occurred under a condition in which the ball impact force exceeded a certain threshold value. Moreover, the total ball impact energy was positively correlated with co-crystal formation, exhibiting a higher ball impact force than the threshold value. The kinetics of co-crystal-2 formation was almost consistent with the Jander equation. Consequently, co-crystal-2 formation could be explained according to a three-dimensional diffusion mechanism.
authors.affiliation: Department of Chemical Engineering and Materials Science, Doshisha University, 1-3 Miyakodani, Tatara, Kyotanabe, Kyoto 610-0321, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Shimono
authors.affiliation: Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan. Electronic address: kadota@gly.oups.ac.jp.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kadota
authors.affiliation: Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Tozuka
authors.affiliation: Department of Chemical Engineering and Materials Science, Doshisha University, 1-3 Miyakodani, Tatara, Kyotanabe, Kyoto 610-0321, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Shimosaka
authors.affiliation: Department of Chemical Engineering and Materials Science, Doshisha University, 1-3 Miyakodani, Tatara, Kyotanabe, Kyoto 610-0321, Japan. Electronic address: yshiraka@mail.doshisha.ac.jp.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Shirakawa
authors.affiliation: Department of Chemical Engineering and Materials Science, Doshisha University, 1-3 Miyakodani, Tatara, Kyotanabe, Kyoto 610-0321, Japan.
authors.forename: Jusuke
authors.initials: J
authors.lastname: Hidaka
mesh_terms: D002110:Caffeine / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D019343:Citric Acid / Q000737:chemistry*; D003460:Crystallization; D018360:Crystallography, X-Ray; D007700:Kinetics; D008956:Models, Chemical; D033362:Powder Diffraction; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D019343:Citric Acid; D002110:Caffeine
keywords: Impact energy; Jander equation; Mechanochemistry; Planetary ball mill