Prediction of apparent equilibrium solubility of indomethacin compounded with silica by 13C solid state NMR

The apparent equilibrium solubility (AES) of indomethacin increased by co-grinding with silica. Change in the long- and short range disorder of indomethacin by co-grinding was examined by X-ray powder diffraction and 13C solid state NMR, respectively, to elucidate the increased AES. Since the increase in AES was particularly marked after complete disappearance of X-ray diffraction peaks, we attributed the enhanced AES primarily to the short range disorder on the molecular basis. This was confirmed by a high correlation between the standardized full width at half maximum (SFWHM) of the specific peaks observed by 13C solid state NMR and log (AES). The correlation enables the prediction of AES as well.