In-situ X-Ray Diffraction Investigation of Thermal Degradation in Medicinal Products

Most manufacturers of common over-the-counter pharmaceuticals recommend storing the medicines below temperatures of 25 – 30 °C. In many parts of the world, the ambient tempera-tures regularly exceed this threshold. The investigation of the thermal stability of everyday consumer products is therefore an essential step during the development and in quality control of pharmaceuticals. This report shows that non-ambient X-ray powder diffraction (XRD) is a power-ful and versatile tool for such stability studies.


Temperature is one of the most important conditions when it comes to proper storage of almost all materials. Organic materials, such as medicines, are often particularly vulnerable to high temperatures; for example, most common over-the-counter pain killers should not be stored at temperatures above 25 °C.1

This temperature is frequently exceeded in many parts of the world and with the increase in global average temperatures over the last decades, the number of days that exceed this upper limit are steadily increasing.2,3 In particularly hot environments, such as cars parked in direct sunlight, temperatures up to 80 °C can even be reached.4

As most common active pharmaceutical ingredients (APIs) are crystalline materials, structural changes can easily be investigated by X-ray powder diffraction (XRD). Applying in-situ high-temperature XRD allows the structural investigation of the behavior of materials at high temperatures and can be used to identify possible reversible and irreversible phase changes.

In this report, the high temperature behavior of several pharmaceutical samples is investigated using the Automated Multipurpose Powder X-Ray Diffractometer XRDynamic 500 and the High-Temperature Oven Chamber HTK 1200N. HTK 1200N is an oven chamber with an extremely homogenous temperature distribution over the whole chamber interior. It allows measurement of samples up to 1200 °C and can also be fitted with an optional capillary extension which is ideal for the measurement of organic materials (such as pharmaceuticals), sensitive materials, or samples where only a small quantity of material is available.

The goal is to test the stability of pharmaceutical materials above the recommended maximum storage temperature and to determine any possible phase changes that occur. 


1. Médecins Sans Frontières (2011): Essential drugs - practical guidelines. ISBN 978-2-37585-145-6, (accessed 04.02.2022)
2. National Centers for environmental information: State of the climate. (accessed 04.02.2022)
3. Climate Central (2019): More Extremely Hot Days. (accessed 04.02.22)
4. Waleed, A-F, Soubhi, H.: Temperature variations, inside a parked car in hot and dry climates. International Journal of Automobile Engineering Research & Development (IJAuERD), 3, 75-80, 2013

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