Comparative determination of polymorphs of indomethacin in powders and tablets by chemometrical near-infrared spectroscopy and x-ray powder diffractometry.

The purpose of this research was to develop a rapid chemometrical method based on near-infrared (NIR) spectroscopy to determine indomethacin (IMC) polymorphic content in mixed pharmaceutical powder and tablets. Mixed powder samples with known polymorphic contents of forms alpha and gamma were obtained from physical mixing of 50% of IMC standard polymorphic sample and 50% of excipient mixed powder sample consisting of lactose, corn starch, and hydroxypropylcellulose. The tablets were obtained by compressing the mixed powder at 245 MPa. X-ray powder diffraction profiles and NIR spectra were recorded for 6 kinds of standard materials with various polymorphic contents. The principal component regression analysis was performed based on normalized NIR spectra sets of mixed powder standard samples and tablets. The relationships between the actual and predicted polymorphic contents of form g in the mixed powder measured using x-ray powder diffraction and NIR spectroscopy show a straight line with a slope of 0.960 and 0.995, and correlation coefficient constants of 0.970 and 0.993, respectively. The predicted content values of unknown samples by x-ray powder diffraction and NIR spectroscopy were reproducible and in close agreement, but those by NIR spectroscopy had smaller SDs than those by x-ray powder diffraction. The results suggest that NIR spectroscopy provides a more accurate quantitative analysis of polymorphic content in pharmaceutical mixed powder and tablets than does conventional x-ray powder diffractometry.