Amorphous or nanocrystalline? Advances in total scattering pair distribution function methods for characterizing amorphous and nanocrystalline pharmaceuticals

Speaker: Simon J.L. Billinge, PhD
Professor, Materials Science & Engineering, Applied Physics & Applied Mathematics
Columbia University
(Host: Prof. Lian Yu)

Abract: In the solid state, small molecules such as active pharmaceutical ingredient (API) molecules tend to pack in well defined arrangements leading to different crystalline polymorphs. An alternative solid form, increasingly of interest in the pharmaceutical industry, is the amorphous state. This state is characterized by a broad and largely featureless XRD pattern, the so-called “amorphous halo’, devoid of Bragg-peaks due to the lack of long-range order in the packing. There is a further, intermediate situation, which that of ultra-small nanoparticulate solid drugs.  These also give broad and featureless XRD patterns, but actually have order over a few nm lengthscale.  

A major challenge in bringing drugs to market in the amorphous form is the lack of a reliable method for fingerprinting, let alone carrying out a more complete structural characterization of, these materials.  We have recently been exploring whether total scattering atomic pair distribution function methods (TSPDF) can alleviate this bottleneck.  TSPDF uses short wavelength x-rays to obtain a scattering pattern of sufficient quality that can be Fourier transformed to obtain a meaningful real-space pair distribution function that shows the distribution of atomic distances in the solid. We found that the approach is highly promising and provides additional information not available in a conventional XRD approach in the case of amorphous API’s.  I will describe the method and show our results on a range of materials from more simple to more complex molecules.  It is possible to differentiate truly amorphous from nanocrystalline forms and learn a surprising amount about the underlying molecular packing.