Crystal Structure Determination in Solid Form Drug Development

Single crystal structure solution using X-ray diffraction analysis (SC-XRD) plays an important role in drug development. SC-XRD fully elucidates the molecular structure and can be used to confirm successful chemical synthesis of the molecule. Many drug molecules are chiral. In addition to being the most reliable, SC-XRD is the only generally applicable method to determine the absolute configuration, i.e. the three-dimensional structure of the molecular bonds.

Using hybrid pixel single photon counting detector technology and current computational methods, the absolute configuration can almost always be determined unambiguously in just a few hours – even for molecules where the heaviest atoms are carbon, nitrogen, and oxygen.

Growing a sufficiently large, good quality, single crystal can sometimes still be a challenge and a bottleneck, even when crystals smaller than 100-μm can now routinely be used. Several growing techniques will be discussed in this upcoming webinar.

For certain purposes, a full structure solution is not always needed, thereby circumventing the need for a single crystal. Given high resolution powder X-ray diffraction (PXRD) data, most often the unit cell parameters and space group can be determined by finding an indexing solution to the observed peak positions, also known as indexing. The resulting unit cell volume can be used to identify the contents and stoichiometry, important information while performing solid form screens. The index of a PXRD pattern reveals if extraneous Bragg peaks exist, indicating form impurities. Conversely, the indexing solution can be used to determine if the powder sample consists of a single, crystalline phase; an important aspect of form designation.

In patents, solid forms are usually claimed by lists of characteristic peaks in the PXRD. Collecting PXRD data is often straightforward, though pitfalls exist. Peaks should be chosen based on the allowed peak positions as governed by the crystal structure of the claimed form either supported by a SC-XRD structure or by an indexing solution to the PXRD.

Join this webinar to learn more!

Speaker

Dr. Steef Boerrigter, Senior Research Scientist, AMRI

Dr. Steef Boerrigter is currently a group leader in Materials Science at AMRI West Lafayette. Beyond performing experimental screening for polymorphs, salts and cocrystals, his group specializes in crystal growth for single-crystal structure elucidation. Dr. Boerrigter obtained an M.Sc. at the department of crystallography at Utrecht University. He obtained his PhD in Computational Materials Science from Nijmegen University on the subject of crystal morphology prediction. In 2002 he moved to Antwerp, Belgium where he worked on a Marie-Curie postdoctoral fellowship. He worked as a visiting professor in the Department of Industrial and Physical Pharmacy in the College of Pharmacy at Purdue University and still teaches crystallography as an adjunct assistant professor.

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