X-ray Methods for Understanding Structure-property Relations in Amorphous Drugs

Dr. Chris J. Benmore, X-ray Science Division, Advanced Photon Source, Argonne National Laboratory (Host:  Prof. Lian Yu)

The structural interactions of drug and polymer molecules in orally administered amorphous pharmaceuticals can strongly influence both the stability and solubility of the resulting medicine. Understanding phase relationships between a drug and its polymer host are essential to optimize clinical drug formulations and identify the risk of crystallization [1]. Different amorphous structural forms of the same drug can also influence its properties, necessitating the need for accurate structural characterization methods. High-energy x-ray diffraction provides a direct probe of both the intermediate and short range order in disordered materials. Recently, the Advanced Photon Source established a glass, liquid, amorphous materials and extreme conditions program on beamline 6-ID-D. Here the world’s first superconducting high-energy undulator provides a high photon flux and unprecedented resolution in the resulting x-ray pair distribution functions. In addition, the fast x-ray data collection time enables the study of materials at the atomic level in extreme, metastable, and often transient states. Acoustic levitation has been developed at the Argonne to perform single droplet experiments, simulating the drying process in industrial spray driers [2]. Pharmaceutical companies routinely use these technologies to screen the structure of drug formulations to identify medicines likely to possess high solubility and bioavailability. Current plans to implement second generation undulator devices, x-ray focusing optics as well as SAXS/WAXS capabilities for extended range PDF measurements will be discussed in terms of their implications for future pharmaceutical research.

[1] Advanced X-ray Analytical Methods to Understand Structure and Properties and Risk. In ‘Discovering & Developing Molecules with Optimal “Drug-Like” Properties’ Chapter 9. C. J. Benmore. Editor: S.R. Byrn. American Association of Pharmaceutical Scientists, Springer (2014) ISBN 978-1-4939-1398-5.

[2] Structural characterization and aging of glassy pharmaceuticals made using acoustic levitation. C.J. Benmore et al. J. Pharma. Sci. 102 (2013) 1290.