New possibilities for X-ray analysis

X-ray powder diffraction (XRPD) is a key analytical technique in the pharmaceutical industry, providing direct information about the crystalline and amorphous components in pharmaceutical formulations in a non-destructive manner and without laborious sample preparation. The technique has been used for many years in the research environment because XRPD patterns form an essential part of a patent application. In addition, it is widely used for polymorph screening using well plates and during scale-up from the laboratory to the production environment.

Several possibilities, however, exist to expand the uses of the technique, including the rapid and non-destructive distinction between original and counterfeited pharmaceutical formulations, as well as direct visualisation using computed tomographic techniques. A further new and exciting possibility with X-ray diffraction is its ability to distinguish between different amorphous forms using Pair Distribution Function analysis. With the addition of controlled-environment cells to a diffractometer, direct and non-destructive observation of phase changes as a function of changing temperature and/or humidity becomes possible.

Like XRD, X-ray fluorescence (XRF) spectroscopy is a non-destructive technique that requires simple or even no sample preparation. Measurements can be made with as little as 100 mg of material. It detects and quantifies major and minor elements in fillers, lubricants, coatings and other excipients down to sub-ppm levels. XRF can also be applied to the high precision quantification of catalyst residues present in active ingredients or final drug products. Fingerprinting in addition allows rapid scan based identification of all materials including excipients, APIs and raw materials.

As with any technique, barriers to the uptake of XRD and XRF in the pharmaceutical industry are often connected to regulation and standardisation of methodology. However, 21 CFR part 11 ready solutions, in-house expertise for IQ, OQ and validation assistance (DQ/PQ), and product ranges designed to exceed research and compendia requirements are already helping workers make the move to X-ray analysis — and this looks set to continue in 2010.

Recent advances
Technology developments, such as the ultra-fast detectors allowing data collection in minutes, combined with advances in analysis software have allowed X-ray techniques to expand their role such that today, both XRD and XRF are recognised as adding value in many areas of drug discovery, development, manufacturing and quality control. More recent innovations, such as the addition of computed tomography to diffraction data, are now allowing the detailed investigation of formulation morphology, without the need for investment in additional dedicated instruments.

We definitely see a future where XRD and XRF are even more embedded into the industry. Pharmaceutical companies have always depended on a range of analysis technologies, and in recent years an increasing regulatory burden and the need to understand complex formulations has stimulated the need for additional, insightful data. X-ray analysis can deliver on these needs with powerful, discriminating and non-destructive analysis.

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