Quantitative determination of hydrate content of theophylline powder by chemometric X-ray powder diffraction analysis.

The purpose of this study was to establish a calibration model to predict the hydrate content in powder materials consisting of anhydrate (theophylline anhydrate (THA)) and theophylline monohydrate (THM) by using various kinds of X-ray powder diffraction (XRPD) analytical methods. XRPD profiles were measured five times each for 11 standard samples containing of THA and THM. THM content in the standard samples was evaluated based on XRPD profiles by the diffraction peak height and area methods, and the Wakelin's and principal component regression (PCR) methods, respectively. Since THA and THM were cube- and rod-shaped particles, the standard samples consisted of THA and THM showed crystal orientation due to THM crystal shape. THA showed reproducible XRPD profiles, but THM showed fluctuating intensities in some specific peaks in the profiles. The linear calibration models were evaluated based on calibration XRPD datasets of the standard materials by various methods. In the result based on validation XRPD datasets, the order of the mean bias and the mean accuracy were peak height > peak area > Wakelin's > PCR, indicating that PCR was the best method to correct sample crystal orientation. The effectiveness of the PCR method in construction of calibration models was discussed by a scientific approach based on regression vectors.