X-ray diffraction (XRD) is a popular technique for determining the exact structure of molecules and is effective on different samples. The method has multiple features and strengths that support a range of applications.

Specifically, XRD is a fundamental analytical technique in the pharmaceutical and industrial sectors. If you want to know more, this guide will help you understand the principles, strengths, weaknesses, and applications of XRD.

What is X-Ray Powder Diffraction?

X-ray powder diffraction is a versatile analytical technique often used for accurate phase identification of crystalline materials. It also provides detailed information on cell dimensions. Analyzing samples using powder, X-ray diffraction offers essential information that complements several spectroscopic and microscopic techniques.

This method can direct other methods like morphology, phase identification, sample purity, and crystallite size. When used as a bulk technique, XRD provides information that correlates with microscopy data to determine if the microscopic information of fewer particles represents the majority sample.

Principles of X-Ray Diffraction

In the 19th century, scientists discovered that crystalline particles act as 3D diffraction substances when exposed to X-Ray wavelengths. While X-ray machines have been overtaken by newer technology like MRIs, they’re still valuable for other fields. The behavior is similar to what was observed with spaced planes in a crystal lattice. Since then, X-ray diffraction has become a popular technique in the study of atomic spacing and crystal structures.

Typically, X-ray diffraction is based on a crystalline sample’s orderly interference of monochromatic wavelength. The X-rays come from a cathode tube, converted into monochromatic radiation through filtration, concentrated, and focused on the target sample. The subsequent interaction of these rays with the crystalline sample leads to a constructive interference when all the experimental conditions satisfy Bragg’s Law.

The law unites the electromagnetic radiation wavelength and the diffraction angle and relates them to lattice spacing in the crystalline sample under study. The diffracted rays are accurately detected, counted, and processed. When you scan the sample through different angles, you should identify all possible lattice diffractions because of the randomness of the powdered sample.

Since each mineral has unique lattice spacing, it’s possible to identify any sample by comparing the lattice spacing with a database of standard reference patterns. However, the angle of incident and diffracted rays is critical in all diffraction methods.

How an X-Ray Diffraction Instrument Works

X-ray diffractometers comprise three components: a cathode ray tube, a sample holder, and an X-ray wavelength detector. When the filament in a cathode ray tube is heated, it produces some electrons, which are then accelerated to bombard the sample. Once the electrons have attained enough energy to penetrate the inner electrons in the sample material, a specific spectrum is produced. The spectra have different wavelengths and intensities.

Typically, the wavelengths are unique for specific sample materials. For diffraction to occur, filtration by crystal monochromators and foils is necessary to generate monochromatic rays necessary for accurate diffraction. Once the instrument focuses on the X-rays, it directs them to the sample. The detector rotates along with the sample while the device records the intensity of refractions. As soon as the subsequent geometry from incident rays satisfies Briggs Law, constructive interference occurs. The detector processes the incoming signal and converts it into a countable rate that is transmitted to a monitor or printer.

X-Ray Diffraction Applications

X-ray diffraction methods are commonly used to identify unknown crystalline substances such as inorganic compounds and minerals. Accurate identification of unknown compounds and substances is vital in environmental science, geology, biology, engineering, and material science. Other applications may include:

  • Characterization and classification of crystalline substances
  • Identifying fine-grain minerals that can’t be hard to determine visually
  • Measuring sample unit purity
  • Determining cell dimensions

However, experts can also use specialized XDR techniques to perform advanced tasks. Typically, XDR is reliable in quantitative analysis to find out modal amounts in minerals and determine crystal structures. It can be used to determine lattice mismatch and detect dislocation density. Unlike in the past, where X-rays had a significant role in medicine, modern equipment is sophisticated and accurate, like the proton beam machines for cancer treatment.

Relative Humidity and Variable Temperature

Solid-phase transitions can be examined using X-ray diffractometers through varying temperature stages. Elevated and sub-ambient temperature methods are efficient in the study of sample behaviors at different temperatures.

This technique helps in the direct identification of crystalline phases relative to temperature. It’s also used when investigating the structures of various hydrates that are crystalline. The water found in the hydrates comes from changes in relative humidity within the sample structure.

Peaks in wavelength diffractions stem from the humidity and substances can be identified by comparing the patterns with a benchmarking pattern database.

Pharmaceutical Industry

XRD is also used in drug analysis, and it’s a reliable process used in the development, testing, and production of drugs. Every drug goes through quality control and analysis of active ingredients and excipients of the product. Slight changes in the production stages often cause inconsistencies in different batches of the same drug. Consequently, this can lead to severe problems in the medicines’ dosage, formulation, and bioavailability.

Most drug formulations contain multiple ingredients that vary in physical properties. These differences can have massive impacts on the efficacy and quality of the drug. To ensure uniformity and quality, manufacturers often use XRD to analyze and screen pharmaceutical ingredients.

Pros and Cons of X-Ray Diffraction

While XRD continues to be a robust and versatile analytical technique, it has its strengths and weaknesses.


  • It’s a powerful and reliable technique for identifying ambiguous materials
  • It requires little sample preparations
  • XRD instruments are readily available
  • Data interpretation and presentation is simple


  • Requires a standard database for accurate reference
  • Peak overlays can occur in some reflections
  • When the material has multiple substances, the detection is only 2%


The continuous improvements in XRD software and instruments make it possible to analyze substances accurately. Particularly, XRD is a vital technique in the pharmaceutical industry. Besides helping identify unknown substances, XRD ensures the quality and uniformity of drugs.