Thermal analysis and FTIR spectral curve-fitting investigation of formation mechanism and stability of indomethacin-saccharin cocrystals via solid-state grinding process

详细信息	查看全文 | 推荐本文 |

• 作者：Gang-Chun Zhang ; Hong-Liang Lin ; ^{hllin@mail.ypu.edu.tw} ; Shan-Yang Lin ; ^{sylin@mail.ypu.edu.tw}
• 关键词：Curve-fitting ; DSC ; Cocrystal ; Cogrinding ; Indomethacin ; Saccharin ; Formation mechanism ; Thermal effect ; Stability
• 刊名：Journal of Pharmaceutical and Biomedical Analysis
• 出版年：2012
• 期刊代码：65_07317085
• 类别：ch
• 出版时间：July, 2012
• 卷：66
• 期：Complete
• 页码：162-169
• 文件大小：788 K

摘要

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^鈭? and 1693 to 1682 cm^鈭? for IMC, as well as from 3094 to 3136 cm^鈭? and 1718 to 1735 cm^鈭? 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 掳C for the 30-min IMC-SAC ground mixture was almost the same as the melting at 184 掳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 掳C/40%RH condition for 7 months had an improved tendency of IMC-SAC cocrystallization.