X-Ray Diffraction (XRD)

X-ray diffraction (XRD analysis or XRPD analysis) is uniquely used for determination of crystallinity of a compound: 

  • I.D. of crystalline material (used for regulatory purposes or during development.) 
  • I.D. of different polymorphic forms (“fingerprints” ). 
  • Distinguishing between amorphous and crystalline material 
  • Quantification of the percent crystallinity of a sample 
  • Quantification and qualification of polymorphic forms present in the sample 
  • Quantification and qualification analysis of crystalline chemical compounds present in the samples 
  • Analysis of crystalline structure of material 
  • Verification of co-crystal and crystalline salt formation 
  • Identify a solid-form of drug substance in a dosage form. 
  • Study buffer/solvent induced solid-form transition during dissolution and in suspensions 
  • Study stability of polymorphs in slurries. 
  • Conduct polymorph, salt, co-crystal screenings. 
  • Study phase diagrams for co-crystal scaling up of crystallisation process.  

Knowledge about crystallinity is highly relevant, as a crystalline form is usually preferred in development: In contrast to amorphous material, a crystal has well-defined properties (melting point, solubility and IDR) – parameters that should be known in order to control your final product. The result from an XRD analysis is a diffractogram showing the intensity as a function of the diffraction angles.  Positive ID of a material using XRD analysis is based on accordance between the diffraction angles of a reference material and the sample in question. 

 

For Material Experts: 

Instrument and measuring principle 

XRD analysis is based on constructive interference of monochromatic X-rays and a crystalline sample: The X-rays are generated by a cathode ray tube, filtered to produce monochromatic radiation, collimated to concentrate, and directed toward the sample. The interaction of the incident rays with the sample produces constructive interference (and a diffracted ray) when conditions satisfy Bragg’s Law (nλ=2d sin θ). This law relates the wavelength of electromagnetic radiation to the diffraction angle and the lattice spacing in a crystalline sample. 

The characteristic x-ray diffraction pattern generated in a typical XRD analysis provides a unique “fingerprint” of the crystals present in the sample. When properly interpreted, by comparison with standard reference patterns and measurements, this fingerprint allows identification of the crystalline form.  

Instrument PANalytical X’Pert³ Powder and Multipurpose X-ray Diffractometer Empyrean 
USP/Ph. Eur. Ph. Eur 2.9.33 
Operating range 2-60 °2Theta (if required up to 150 °2Theta) 
Temperature R.T. (temperature chamber available) 
Humidity Ambient (humidity chamber available) 
Sample amount App. 10 mg-200 mg 

Consult our Experts

Dr. Wenbo Wang
QC Chemist

Dr. Anna Shevchenko
Principal Scientist

Literature

Brittain HG (2001) X-ray diffraction III: pharmaceutical applications. Spectroscopy (7):14-8.

Brittain HG (2003) X-ray diffraction of pharmaceutical materials. Profiles of Drug Substances, Excipients and Related Methodology 30:271-319. 

Ivanisevic I, McClurg RB, Schields PJ (2010) Uses of X‐ray powder diffraction in the pharmaceutical industry. In Pharmaceutical sciences encyclopedia: drug discovery, development, and manufacturing 15:1-42.

Thakral S, Terban MW, Thakral NK, Suryanarayanan R (2016) Recent advances in the characterisation of amorphous pharmaceuticals by X-ray diffractometry. Adv Drug Reviews 100:183-93.

Thakral NK, Zanon RL, Kelly RC, Thakral S (2018) Applications of powder X-ray diffraction in small molecule pharmaceuticals: Achievements and aspirations. J Pharm Sci 107(12):2969-82.

Phadnis NV, Cavatur RK, Suryanarayanan R. Identification of drugs in pharmaceutical dosage forms by X-ray powder diffractometry. Journal of pharmaceutical and biomedical analysis. 1997 Apr 1;15(7):929-43.

Surana R, Suryanarayanan R (2000) Quantitation of crystallinity in substantially amorphous pharmaceuticals and study of crystallisation kinetics by X-ray powder diffractometry. Powder Diffr 15(1):2-6. 

Scroll to Top