title: Dehydration, hydration behavior, and structural analysis of fenoprofen calcium.
abstract: Fenoprofen calcium (FC) is a nonsteroidal, anti-inflammatory, analgesic, and antipyretic agent. The dehydration behavior of FC dihydrate and the rehydration of the dried FC were investigated using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and powder X-ray diffractometry (PXRD). The stoichiometry, the crystal packing arrangement, and water environments in FC dihydrate were determined using single-crystal X-ray diffraction (XRD) analysis. The Arrhenius plot (natural logarithm of the dehydration rate constant versus the reciprocal of absolute temperature) for FC dihydrate from isothermal TGA is not linear. The activation energy of dehydration was 309 kJ/mol in the 50-60 degrees C range and 123 kJ/mol in the 60-80 degrees C range. The difference in activation energy can be explained from the crystal structure data where one water molecule is sandwiched between repeating polar carboxylate groups and the other water is in a slightly less polar region of the crystal. Single-crystal XRD analysis also indicated each calcium ion is coordinated to six oxygens. Two coordinating oxygens are provided by two water molecules and the other four oxygens are provided by the carboxylate group of four separate fenoprofen anions. Each fenoprofen anion, which can provide two oxygens for coordination, is associated with two different calcium ions. Hot-stage PXRD suggested that only a loss of 1 mole of water per mole of FC dihydrate (forming a monohydrate) was required to convert the material to a partially crystalline state. The monohydrate is not completely disordered as evidenced by a strong diffraction peak as well as some weaker peaks in the PXRD pattern. The rehydration of the anhydrous form of FC follows a solution-mediated transformation, prior to crystallizing as the dihydrate.
authors.affiliation: Pharmaceutical Development Discovery and Analytical Sciences Departments, Glaxo Wellcome Inc., Five Moore Drive, Research Triangle Park, North Carolina 27709, USA.
authors.forename: H
authors.initials: H
authors.lastname: Zhu
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.forename: P
authors.initials: P
authors.lastname: Varlashkin
authors.forename: S
authors.initials: S
authors.lastname: Long
authors.forename: C
authors.initials: C
authors.lastname: Kidd
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D003460:Crystallization; D005279:Fenoprofen / Q000737:chemistry*; D013818:Thermogravimetry; D014961:X-Ray Diffraction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005279:Fenoprofen