Polymorph Identification by X-Ray Diffraction (XRD)
X-ray diffraction (XRD) is one of the oldest and most reliable techniques to identify polymorphs. When a crystalline powder is exposed to an x-ray beam, it produces a diffraction pattern that is unique to that crystalline form. By comparing that pattern to a library of patterns from known substances, the unknown polymorph can be identified with a high degree of certainty. If the substance is intermixed with other materials such as excipients, each produces its own pattern that superimposes without modification on the individual patterns from each of the components. As a result, the target material can still be identified since its pattern remains intact.
Our laboratory utilizes three state-of-the-art instruments manufactured by Panalytical B.V.. Each instrument utilizes a Si strip detector that permits rapid data collection without sacrificing resolution. In turn, these detectors now make it feasible to use very long scan times when trying to detect low levels of a particular polymorph, which is especially useful when working near the lower detection limit. Also, each instrument has a robotic sample changer for unattended analysis of a large number of samples overnight.
Each polymorph produces a unique diffraction pattern like that shown here. From such patterns, the peak positions and relative intensities are recorded, which then allows us to compare the pattern against other known materials for a positive identification. If the material is intermixed with other substances such as excipients, the diffraction pattern will be scaled in proportion to its weight fraction, but the feature set (peak positions and relative intensities) will remain intact. Thus, the polymorph of the active pharmaceutical ingredient can be identified, even in the presence of other phases. The limit of detection is of the order of 1%, but under favorable circumstances can be pushed as low as 0.05%.