Quantitative evaluation of curved tablets using x-ray diffraction

Manufacturing processes of pharmaceutical tablets may change the morphology of the crystalline state of the active pharmaceutical ingredients (API) or the excipients. As this can affect the bio-availability of the drug, there is an increasing need to analyse the final oral dosage form. This article shows that it is possible to use x-ray diffraction for quantitative analysis of the API in tablets, even if those tablets have a curved surface.

As a typical example tablets containing Indometacin and non-active excipients were measured. The samples were prepared by Mrs I Fix and Prof. K-J Steffens (Institute for Pharmaceutical Technology, Reinische Friedrich-Wilhelms University, Bonn, Germany).

The Indometacin particles had a mean size of 3 µm. Because the tablets had a curved surface the measurements were made on a parallel beam geometry system. A parafocussing Bragg-Brentano geometry would have lead to large defocussing aberrations in the measurements.

For the quantitative analysis the peak area intensity of the Indometacin (0 2 2) reflection at 2q = 21.80 for seven different Indometacin concentrations was determined.

A good least squares fit (a coefficient of determination R2 close to one) was obtained for the mirror-mirror geometry.

This calibration line allows the determination of the Indometacin concentration with an accuracy of approximately ±0.2%, almost one order of magnitude better than legally required. With the mirror-mirror geometry, however, about 30 minutes of measurement time is needed for determining one concentration. When the 2q range is kept small, it is possible to replace the refracted beam mirror with an X'Celerator and limit the irradiated area on the sample. In this way, comparable results are obtained in less than one minute, with a minor loss in accuracy.