Potential of synchrotron X-ray powder diffractometry for detection and quantification of small amounts of crystalline drug substances in pharmaceutical tablets.

The purpose of this study was to develop a sensitive system for detection of crystalline drug substances in intact pharmaceutical tablets by X-ray powder diffractometry (XRPD), using synchrotron X-rays. Fenoprofen calcium dihydrate was used as a model compound. The wavelength and path length of X-rays from synchrotron radiation were optimized in order to maximize the potential of the synchrotron radiation. The optimum wavelength and path length for the measurement of fenoprofen calcium dihydrate were found to be 0.69817 Å and 6.0 mm, respectively, based on theoretical calculations. Under the optimized conditions, a limit of quantification of 0.05% (RSD=9.4%, n=3) and a limit of detection of 0.02% (RSD=17.3%, n=3), results which are approximately 10² times as sensitive as those obtained using conventional XRPD instruments, were achieved. The technique was also applied to fenoprofen calcium dihydrate detection in intact film-coated tablets, which contained Ti in the coating film, and a limit of detection of 0.02% was again attained.