Crystalline structure influences nearly every important solid-state property, including stability, dissolution, manufacturability, polymorphism, particle interactions, and intellectual property. Selecting the appropriate diffraction technique requires understanding not only what information each method provides, but also the limitations imposed by crystal size, crystallinity, sample preparation, and the scientific question being asked. Triclinic Labs combines decades of crystallographic expertise with one of the industry's broadest collections of diffraction techniques—including X-ray powder diffraction (XRPD), single-crystal X-ray diffraction (SCXRD), and microcrystal electron diffraction (MicroED)—to generate scientifically defensible structural information for pharmaceutical development, manufacturing investigations, patent support, and regulatory submissions.
The content of this page has been scientifically reviewed by Steef Boerrigter, Ph.D., Research Fellow & Head Crystallographer at Triclinic Labs · Updated 8/1/2026
XRPD measures how X-rays scatter from ordered atomic planes in a crystalline solid and offers a unique fingerprint for each crystalline phase. XRPD can assess the degree of crystallinity, and XRPD patterns can be indexed to determine the unit cell. Further offerings include quantitative phase analysis and non-ambient studies.
Use XRPD for polymorph identification, hydrate/solvate monitoring, crystallinity checks, drug-product lot comparison, mineral/phase identification, and release or stability methods where the crystal form is the quality attribute.
XRPD is weaker for amorphous materials and for detecting low-level impurities—especially non-crystalline impurities—in excipient-rich matrices. Raman spectroscopy, infrared (IR) spectroscopy, differential scanning calorimetry (DSC), solid-state nuclear magnetic resonance (ssNMR) spectroscopy, microscopy, or chromatography can be used as orthogonal evidence.
Typically between 10 and 100 mg.
Raman spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, ssNMR, DSC, thermogravimetric analysis (TGA), microscopy, MicroED, and SCXRD can complement XRPD depending on whether the question is phase identity, structure, thermal behavior, molecular environment, or morphology.
FDA cares that the method is specific for the relevant form in the real matrix, that sample preparation does not convert the form, and that validation or verification supports the intended release, stability, comparability, or chemistry, manufacturing, and controls (CMC) decision under International Council for Harmonisation (ICH) Q2(R2)/Q14 principles.
A common mistake is to confuse structural differences, instrumental effects, and preferred orientation as causes of peak-intensity differences. Another common mistake is to confuse sample-displacement error with real structural differences as the cause of shifts in 2θ peak angles. One of the most damaging mistakes is to assign new polymorphic forms to XRPD patterns that actually arise from mixtures or severe preferred orientation.
Triclinic uses diffraction and crystallographic analysis to solve real-world solid-form problems involving polymorphs, salts, cocrystals, hydrates, solvates, crystallinity, amorphous content, and phase changes during processing or storage. XRPD is applied to form selection, patent support, stability risk, formulation troubleshooting, and quality investigations.
The table below lists the specific platforms, brands, models, software, detectors, and capability notes relevant to this service area.
| Instrument or platform | Brand, model, software, or detector | Additional capabilities and use |
|---|---|---|
| X-ray powder diffraction | Rigaku SmartLab instruments; quadruple-redundant XRPD capacity; Cu anode X-ray sources; reflection and transmission goniometer geometries. | Phase identification, crystallinity, quantitative/semi-quantitative phase analysis, texture/microstructure, tablets, powders, thin films, and drug-product mapping. |
| Photon-counting 2D detection | Rigaku HyPix-3000 detector | High-count-rate, fast-readout, essentially no-noise photon-counting detection for advanced diffraction studies. |
| Non-ambient sample stage | Anton Paar CHC+ temperature and humidity control with liquid-nitrogen cooling and vacuum attachment | 2%–95% RH and −10–95 °C combined temperature and relative-humidity control; vacuum, air, or inert atmospheres; and program-controlled or continuous VT/VRH collection strategies. |
| cGMP and non-GMP XRPD capacity | Four powder X-ray diffractometers; three cGMP and one non-GMP system with 2D detector | Routine release/validation-ready XRPD plus advanced variable-temperature, variable-humidity, and 2D materials studies. |
| MicroED structure determination | ELDICO ED-1 MicroED system | Unit-cell and crystal-structure determination from nanocrystalline material when suitable single crystals are unavailable. |
| Single-crystal X-ray diffraction | Bruker D8 Quest diffractometers with copper and molybdenum X-ray sources | Atomistic crystal-structure solution and absolute-configuration determination for chiral compounds. |
| Argonne National Laboratory synchrotron access | High-resolution XRPD | Patent-litigation support. |
This example shows the temperature-induced phase transformation of theophylline.
These examples include technical resources, regulatory guidances, or literature relevant to the technique. Download buttons are placed at the bottom-left of each example.
Author: Triclinic Labs
Publication date: 2023
Abstract: Application note showing how VT/VRH-XRPD follows theophylline phase transitions under controlled humidity and temperature. The example supports using non-ambient diffraction to evaluate hydrates, anhydrates, stability boundaries, and process-relevant phase transformations.
Author: Triclinic Labs
Publication date: 2023
Abstract: Crystalline materials give distinctive diffraction fingerprints; peak positions and intensities support phase identification, while experimental details and sample handling affect interpretation.
Author: International Council for Harmonisation / FDA
Publication date: 2024
Abstract: FDA notes that ICH Q2(R2) and Q14 describe validation and development principles for analytical procedures used to assess drug substance and drug product quality. These guidances frame FDA expectations for specificity, accuracy, precision, range, robustness, lifecycle management, and fit-for-purpose method evidence.
Author: G. Patrick Stahly, Ph.D.
Overview: How source wavelength affects diffraction angle, low-angle features, and peak separation for closely related crystalline phases.
Author: G. Patrick Stahly, Ph.D.
Overview: How instrument noise, matrix behavior, validation mixtures, and replicate detection support defensible XRPD limits.
Characterizes density, flow, particle size, moisture response, surface behavior, and morphology to explain powder handling and manufacturing performance.
View techniqueDetermines molecular and crystal structures from sub-micron crystals when conventional single-crystal analysis is not practical.
View techniqueMeasures melting, glass transitions, crystallization, solvent loss, and decomposition to connect thermal behavior with stability and processing.
View techniqueQuantifies water, distinguishes bound from surface moisture, and evaluates sorption, desorption, hydrate formation, and humidity-driven change.
View techniqueProvides rapid molecular-identification, functional-group, solid-form, mixture, and spatial-distribution evidence using Raman, FTIR, IR imaging, and UV/Vis.
View techniqueProvides atomic-level connectivity, identity, quantitative, impurity, peptide, formulation, and solid-state evidence through solution- and solid-state NMR.
View technique
Tell Triclinic what sample you have, what decision the data must support, what prior data are available, and whether cGMP, release, validation, or regulatory documentation is required.
