Comparative evaluation of the degree of indomethacin crystallinity by chemoinfometrical Fourier-transformed [corrected] near-infrared spectroscopy and conventional powder X-ray diffractometry.

A chemoinfometrical method for evaluating the degree of crystallinity based on Fourier-transformed [corrected] near-infrared (FT-NIR) spectroscopy was established and compared with the conventional powder X-ray diffraction method. Powder X-ray diffraction profiles and FT-NIR spectra were recorded for 11 kinds of standard materials with various degrees of crystallinity obtained by physically mixing crystalline and amorphous indomethacin (IMC). Chemoinfometric analysis was performed on the FT-NIR spectral data sets by multiple linear regression (MLR) (MLR-Set-Up Search program). The crystalline and amorphous forms showed significant NIR spectral peaks. MLR analysis was performed based on normalized NIR spectra sets for standard samples of known crystallinity. A calibration equation was determined to minimize the root mean square error of prediction. The predicted crystallinity values were reproducible and had a smaller standard deviation. The values of crystallinity predicted by X-ray powder diffractometry and FT-NIR spectrometry suggested a satisfactory correlation between the 2 techniques. The results indicated that FT-NIR spectroscopy provides for an accurate quantitative analysis of crystallinity compared with conventional X-ray diffractometry.