X-ray powder diffraction

Shine X-rays at a powder full of tiny crystals and they bounce off the regularly spaced layers of molecules, reinforcing each other only at specific angles — much like ripples interfering to make a clear pattern. X-ray powder diffraction (XRPD) reads out those angles and intensities as a pattern of peaks that acts as a fingerprint of the crystal's internal structure.

Because each crystalline form spaces its lattice planes differently, every polymorph, hydrate and salt produces its own characteristic peak positions. Comparing an unknown sample's pattern to references is the definitive way to identify which solid form is present and to detect form changes. An amorphous solid, having no long-range order, gives no sharp peaks — only a broad diffuse halo, so XRPD also reveals and roughly quantifies crystallinity.

In preformulation and quality control, XRPD is the reference method for solid-form identity, complementing the thermal information from differential scanning calorimetry. Its honest limits include preferred orientation (plate or needle habits can distort relative peak heights), reduced sensitivity to small amounts of one form mixed in another, and the need for careful sample preparation; variable-temperature or humidity XRPD is used to watch form conversions happen in real time.