Estimation of crystallinity of indomethacin by usage of terahertz time-domain spectroscopy and calibration curve: Correlation between crystallinity and solubility

It is well known that the crystalline state of pharmaceutical materials affects their solubility. In this study, to evaluate the accuracy of crystallinity calculated from a calibration curve prepared using terahertz time-domain spectroscopy (THz-TDS), we studied the correlativity of crystallinity measured using THz-TDS and solubility of indomethacin. The crystallinity of indomethacin was changed by storing the amorphous sample at 90 degrees C or 110 degrees C for 5 min to 6 h or 2 min to 2 h, respectively. From the crystallinity and solubility measurement results, it was found that the crystallinity and dissolution profiles after 1 h were equivalent at a storage temperature of 90 degrees C and that after 15 min were equivalent at a storage temperature of 110 degrees C. Thus, the correlation between the crystallinity and the solubility of the sample with a shorter storage time was investigated. To compare the measurement results of the crystallinity and the solubility, we used a general method of linear regression analysis. The crystallinity measured using THz-TDS was plotted on the x-axis and solubility was on the y-axis. From the result of calculation, the correlativity of them was confirmed. This result suggests that the degree of crystallinity calculated from the calibration curve prepared using THz-TDS has practical accuracy.