ABSTRACT
Objective To systematically study solvatomorphism of indomethacin and provide a scientific basis for the quality control of the solvated impurities in this drug. Methods By changing the recrystallization solvent, solvent volume, recrystallization temperature, time and pressure, nine solvates and four non-solvated forms were discovered and prepared. The differential scanning calorimetry (DSC), thermogravimetric analysis ( TGA), X-ray powder diffraction ( PXRD) and infrared spectrometry (IR) were introduced for characterization analysis. Furthermore, the test of influencing factors was used to explore the stability of solvate crystal form and the crystal transformation rules among them. Results Nine solvates were prepared, which including two solvates reported for the first time in this work. Results showed that crystal forms of the 9 solvates have different types or proportions of crystal solvents according to the various results of DSC, TGA, PXRD and IR. Moreover, the nine solvates prepared in this work were metastable crystal forms which could be transformed to non-medicinal forms. Conclusion The composition, thermodynamic property and transformation rule of all the solvates are elucidated in this work. In addition, an effective method for qualitative or quantitative analysis of these solvates was established. The standard graphs and data were used as basic data and scientific basis for the solvate control in the manufacturing of indomethacin.
ABSTRACT
From the view point of drug approval, the research in quality standard and stability of Chinese new drug must be emphasized in order to produce safe and effective new drugs which are competitive in the world. Forthermore, the regulations for new drug approval should be learned repeatedly so as to raise the level of new drug application.