title: Effect of position isomerism on the formation and physicochemical properties of pharmaceutical co-crystals.
abstract: The effect of position isomerism on the co-crystals formation and physicochemical properties was evaluated. Piracetam was used as the model compound. Six position isomers, 2,3-, 2,4-, 2,5-, 2,6-, 3,4-, and 3,5-dihydroxybenzoic acid (DHBA), were used as the co-crystal formers. Co-crystals were prepared on a 1:1 molar ratio by crystallization from acetonitrile. The solid-state properties of co-crystals were characterized using X-ray powder diffractometry (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR). All co-crystal formers formed co-crystal with piracetam except 2,6-DHBA. This failure was possibly due to steric hindrance of two bulk hydroxyl groups and preference of intra-molecular hydrogen bonding formation between hydroxyl group and carboxylic acid group. The XRD patterns of resulting co-crystal indicated that they are highly crystalline and different than parental compounds. Based on the single crystal data, P_23DHBA is orthorhombic while P_24DHBA, P_34DHBA, and P_35DHB belong to monoclinlic system. The hydrogen bonding network patterns of the co-crystals are also different. DSC data showed that the melting temperatures of resulting co-crystals are all lower than that of the starting materials. The melting point rank order of the co-crystals is: P_24DHBA > P_34DHBA > P_23DHBA > P_25DHBA > P_35DHBA.
authors.affiliation: Forest Laboratories, Inc, 49 Mall Drive, Commack, New York 11725, USA. xiangmin.liao@frx.com
authors.forename: Xiangmin
authors.initials: X
authors.lastname: Liao
authors.forename: Mohan
authors.initials: M
authors.lastname: Gautam
authors.forename: Andreas
authors.initials: A
authors.lastname: Grill
authors.forename: Haijian Jim
authors.initials: HJ
authors.lastname: Zhu
mesh_terms: D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D003460:Crystallization; D007536:Isomerism; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010889:Piracetam / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
chemical_list: D004364:Pharmaceutical Preparations; D010889:Piracetam