Intertek ASG Case Study: Pharmaceutical Stability Study using XRD and Hot-Stage XRD

Intertek ASG Laboratory, Manchester, UK

X-Ray Diffraction Case Study:

Pharmaceutical Stability Study using XRD and Hot-Stage XRD

Intertek ASG provides X-ray diffraction analysis for characterization of polymorphs, crystallinity, and orientation, including in-situ studies. GLP and GMP XRD services are available.

X-ray diffraction (XRD) can be extremely effective at monitoring subtle changes in the crystallinity of pharmaceutical materials over a given time period. This is an absolute requirement for formulation work leading to stability trials. Many pharmaceutical products, intermediates and biopharmaceutical products (such as oligonucleotides and DNA) can exist in an amorphous state and the example below is focused upon monitoring an amorphous material over time.

A ‘hot stage’ sample holder is available at Intertek ASG that is capable of heating material up to around 250°C enabling the collection of X-ray diffraction data from samples at elevated temperatures. This allows investigations of polymorphs that only exist above room temperature, as well as studying dehydration, melting and re-crystallising events.

Amorphous Bands of Diffraction:

The diffractogram overlay below shows two amorphous bands of diffraction. Over a given time period the sample is seen to have changed its morphology state showing amorphous bands plus a small amount of crystalline material. This is effectively showing that the sample has started a secondary crystallisation process. The degree of crystallisation can be monitored over a period of time and can be quantitative.

Polymorphism in Pharmaceutical Intermediates and Final Products:

Pharmaceutical intermediates and final products can frequently exhibit polymorphism. XRD is routinely used to observe polymorphic changes that may occur on storage or during a manufacturing process. Temperature and time variations on storage can initiate changes in the original powder pattern. Often formulation of the final stage of the drug delivery system can cause changes to the crystallinity from grinding, packaging or mixing effects. The plot below shows three XRD patterns exhibiting mixtures of polymorphs in a pharmaceutical product.