Powder X-Ray Diffraction (PXRD) Method

Powder X-Ray Diffraction (XRD) is a common technique used to analyze the crystal structure of organic, inorganic, and polymeric materials. This article introduces the principles, components, and applications of PXRD in solid dispersion research.

What is X-Ray Diffraction (XRD) ?

X-Ray Diffraction (XRD) is employed to investigate the crystal structure of materials because the wavelength of X-rays (0.2–10 nm) is comparable to the distance between atoms in a crystalline solid. This technique measures the average spacing between layers or rows of atoms. XRD enables the determination of the orientation of a single crystal or particle, as well as the size and shape of small crystalline regions.
In XRD, an X-ray beam passes through a divergence slit and is directed onto the sample’s surface. The beam is scattered back by the periodic crystal lattice, causing interference and X-ray diffraction. When the incident beam satisfies BRAGG’s law (2dSinƟ = nλ) an X-ray diffraction pattern (peaks or enhanced interference) is obtained.

Where:

d: Spacing between two adjacent atomic planes

Ɵ: Angle of incidence of the X-ray beam relative to the atomic planes

n: Order of diffraction

λ: X-ray wavelength

$Powder X-Ray Diffraction (PXRD) Method - P3$

With a known wavelength (λ), by varying the incidence angle of the X-ray beam until a diffraction pattern is obtained, one can calculate the d-spacing and lattice parameters (h, k, l). By cross-referencing with the International Centre for Diffraction Data (ICDD), the crystal structure, phase composition, identification and quantification of phases, as well as the calculation of crystal size and degree of crystallinity, can be determined…

Powder X-Ray Diffraction (PXRD) is a highly convenient technique for analyzing the crystal structures of organic, inorganic, and polymeric materials. Each crystal possesses a unique atomic arrangement and repeating unit. When exposed to X-rays, these atoms interact with the radiation, producing a series of distinct peaks that clearly identify the crystalline components. Even when two materials share identical chemical compositions, PXRD can differentiate them based on their distinct molecular structures.

Basic Components of PXRD Equipment

The Powder X-Ray Diffraction (PXRD) instrument consists of the following main parts:

X-Ray Source: Uses metal anodes (e.g., copper or molybdenum) to generate monochromatic, high-energy X-rays, ensuring good diffraction quality.
X-ray source/X-ray tube/X-ray generator: Capable of power outputs ranging from 300 W to 4 kW, with voltage levels from 30 kV to 80 kV and current levels from 10 mA to 80 mA, suitable for various applications and sample types.
Soller Slits: Directs the X-ray beam from the source to the sample surface
Sample holder: Holds single or multiple samples and comes in various shapes and sizes to accommodate different samples
Goniometer:

+ Theta–Theta Type: The sample remains fixed while the X-ray source and detector move to ensure that the incidence and reflected angles remain equal (Ɵ).

+ Theta–2 Theta Type: The X-ray source is stationary, while the sample holder and detector move to ensure the reflected angle (2Ɵ) is twice the incidence angle (Ɵ).

+ Goniometers have a maximum scanning angle range of -1100 to +1680, with a minimum step size of 0.00010⁰

$Powder X-Ray Diffraction (PXRD) Method - P3$

Soller Receiving Slits: Directs the reflected X-rays into the detector
Detector: Captures the X-ray diffraction pattern and can be equipped with an SDD detector for quantitative elemental analysis.
Computer and Software: Controls the instrument and analyzes diffraction data
Chiller: Provides cooling for the X-ray source.

Powder X-Ray Diffraction (PXRD) is a convenient technique for analyzing the crystal structure of organic, inorganic, and polymeric materials. Each crystal has a unique arrangement of atoms and repeating units.

When X-rays are directed at the material, the atoms within the crystal structure cause diffraction, producing characteristic peaks on the diffraction pattern. These peaks allow for the identification and analysis of crystalline components.

Even when two materials share identical chemical compositions, PXRD can differentiate them based on their distinct molecular structures. Because PXRD enables rapid measurements on pharmaceutical powders, it is widely employed as a preferred analytical technique in both industrial and academic settings.

Interpreting XRD Patterns

The XRD signal is typically displayed as a graph:
- X-axis: Represents the diffraction angle (2θ), the angle between the incident and diffracted beams, reflecting the spacing between crystal planes according to Bragg’s law.
- Y-axis: Represents the diffraction intensity, indicating the number of X-rays diffracted at a particular 2θ angle. This intensity depends on the electron density in the crystal structure and reveals preferred crystal orientations.
- Peaks: Each peak corresponds to a specific crystal plane. The position (2θ value) and intensity of peaks provide information about interplanar spacings and crystal orientations.

$Powder X-Ray Diffraction (PXRD) Method - P3$

Analysis of XRD Patterns:
- Identify Diffraction Peaks: Sharp, distinct peaks typically indicate high-purity crystalline samples, while broad or overlapping peaks may suggest multiple phases, small crystal sizes, or lattice strain.
- Database Comparison: Use XRD analysis software to compare obtained peaks with standard sample databases (PDF – Powder Diffraction File) to identify crystal phases in the sample.
- Determine Interplanar Spacing: Use Bragg’s law to calculate interplanar spacings from peak positions.
- Estimate Particle Size: Peak broadening is inversely related to particle size; smaller crystals produce broader peaks.
- Assess Purity: The presence of unexpected peaks indicates impurities in the sample.

Applications of PXRD in Pharmaceuticals

In the pharmaceutical industry, PXRD can be used for:

- Crystal Form Identification: Different crystal forms exhibit unique physical, chemical, and biological properties.
- Stability Assessment: Monitor changes in crystal structure during storage.
- Phase Transition Studies: Investigate transitions between crystal forms.
- Quality Control: Ensure the purity and stability of pharmaceutical products.

PXRD is extensively applied in solid dispersion studies:

- Rumondor et al. used PXRD to measure the degree of crystallinity in various amorphous solid dispersions (ASDs) under different storage conditions. They examined the effects of polymers, humidity, and miscibility. Results confirmed molecular dispersion between nifedipine and felodipine with polyvinylpyrrolidone (PVP) in their ASDs.
- PVP and HPMCAS (hypromellose acetate succinate) have been shown to effectively inhibit the crystallization of ASDs containing felodipine. Additionally, amorphous-amorphous phase separation was observed when ASDs were exposed to high humidity, which increased the crystallization tendency of ASDs in stability studies. The inclusion of 5% Eudragit® NE resulted in ASDs containing felodipine exhibiting faster dissolution rates and lower degrees of crystallization compared to ASDs without Eudragit® NE.
- Takeuchi et al. explored the feasibility of time-domain terahertz spectroscopy for crystallinity measurement in ASDs containing nifedipine and compared the results with PXRD. Both methods yielded comparable results.
- Zhu et al. used small-angle X-ray scattering to study crystallization kinetics in ASDs under varying temperature and humidity. Results revealed faster naproxen crystallization at 25°C than at 40°C, while adding polyethylene glycol reduced crystallization rates at 40°C.