title: Thermal analysis and FTIR spectral curve-fitting investigation of formation mechanism and stability of indomethacin-saccharin cocrystals via solid-state grinding process.
abstract: The cocrystal formation of indomethacin (IMC) and saccharin (SAC) by mechanical cogrinding or thermal treatment was investigated. The formation mechanism and stability of IMC-SAC cocrystal prepared by cogrinding process were explored. Typical IMC-SAC cocrystal was also prepared by solvent evaporation method. All the samples were identified and characterized by using differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) microspectroscopy with curve-fitting analysis. The physical stability of different IMC-SAC ground mixtures before and after storage for 7 months was examined. The results demonstrate that the stepwise measurements were carried out at specific intervals over a continuous cogrinding process showing a continuous growth in the cocrystal formation between IMC and SAC. The main IR spectral shifts from 3371 to 3,347 cm(-1) and 1693 to 1682 cm(-1) for IMC, as well as from 3094 to 3136 cm(-1) and 1718 to 1735 cm(-1) for SAC suggested that the OH and NH groups in both chemical structures were taken part in a hydrogen bonding, leading to the formation of IMC-SAC cocrystal. A melting at 184 °C for the 30-min IMC-SAC ground mixture was almost the same as the melting at 184 °C for the solvent-evaporated IMC-SAC cocrystal. The 30-min IMC-SAC ground mixture was also confirmed to have similar components and contents to that of the solvent-evaporated IMC-SAC cocrystal by using a curve-fitting analysis from IR spectra. The thermal-induced IMC-SAC cocrystal formation was also found to be dependent on the temperature treated. Different IMC-SAC ground mixtures after storage at 25 °C/40% RH condition for 7 months had an improved tendency of IMC-SAC cocrystallization.
authors.affiliation: Department of Biotechnology, Yuanpei University, Hsin Chu, Taiwan, ROC.
authors.forename: Gang-Chun
authors.initials: GC
authors.lastname: Zhang
authors.forename: Hong-Liang
authors.initials: HL
authors.lastname: Lin
authors.forename: Shan-Yang
authors.initials: SY
authors.lastname: Lin
mesh_terms: D002152:Calorimetry, Differential Scanning / Q000379:methods*; D003460:Crystallization; D004355:Drug Stability; D004356:Drug Storage; D006860:Hydrogen Bonding; D007213:Indomethacin / Q000737:chemistry*; D012439:Saccharin / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods*; D013696:Temperature; D013997:Time Factors; D044366:Transition Temperature
chemical_list: D012997:Solvents; D012439:Saccharin; D007213:Indomethacin