Structure Determination of Low-molecular-weight Compounds: Crystal Structure Analysis by Powder XRD

Introduction

The evaluation of crystal polymorphism of pharmaceutical compounds is important related to stability and solubility. In general, single-crystal X-ray structure analysis requires single crystals of sufficient size, and measurement may be difficult with co-crystals or unstable crystals. The combination of high-resolution powder diffraction optics using Ge(111) Johansson-type curved crystals, direct-space methods and the Rietveld method makes structural analysis possible even for samples for which crystals of a sufficient cannot be obtained in sufficient sizes as single crystals.

Crystalline phase analysis

Figure 1: Measurement data for γ-indomethacin obtained with a conventional parallel beam optical system (red, upper pattern) and a high-resolution convergent beam optical system (blue, lower pattern). The arrow marks ↓ indicate peaks that cannot be detected with a parallel beam optical system.

Figure 2: Crystal structure of  γ-indomethacin obtained from powder crystal (yellow) and single crystal (orange)

Conclusion

The use of a high-resolution convergent beam optical system enabled to clearly the observation of diffraction peaks of γ-indomethacin that could not be detected by the parallel-beam method (Figure 1). The combined use of direct-space methods and the Rietveld method made it possible to analyze crystal structure from powder samples, even for small molecular compounds for which single crystals are difficult to make. The obtained structures were in good agreement with the single crystal structures (Figure 2). This method is effective as an alternative analysis method in pharmaceutical development, where single crystal growth is a bottleneck.