Related Experiment Video
Updated: May 27, 2026

07:42
On-Chip Crystallization and Large-Scale Serial Diffraction at Room Temperature
Published on: March 11, 2022
Powder X-ray diffraction method for the quantification of cocrystals in the crystallization mixture.
Luis Padrela1, Edmundo Gomes de Azevedo, Sitaram P Velaga
1Department of Health Sciences, Luleå University of Technology, Sweden.
Drug Development and Industrial Pharmacy
|November 19, 2011
Summary
A new powder X-ray diffraction (PXRD) method accurately quantifies cocrystal purity. This reliable technique is essential for assessing solid-state purity in pharmaceutical development, ensuring product performance.
Area of Science:
- Crystallography
- Materials Science
- Pharmaceutical Science
Background:
- The solid-state purity of cocrystals is crucial for their performance.
- Accurate quantification of cocrystal purity in the final product is essential.
Purpose of the Study:
- To develop a powder X-ray diffraction (PXRD) quantification method for cocrystal purity.
- To investigate the formation of indomethacin-saccharin (IND-SAC) cocrystals using mechanochemical methods.
Main Methods:
- Geometric mixing of pure IND-SAC cocrystals with indomethacin/saccharin.
- PXRD measurements using a characteristic diffraction peak for calibration.
- Validation of the calibration model and monitoring cocrystal formation via liquid-assisted grinding (LAG).
Main Results:
- Excellent linearity (R² = 0.9996) was achieved for the IND-SAC cocrystal calibration curve.
- Low limits of detection (LOD: 1.23% w/w) and quantification (LOQ: 3.74% w/w) were determined.
- Validation demonstrated excellent correlation (R² = 0.9981) between actual and predicted concentrations.
Conclusions:
- The developed PXRD method is suitable and reliable for verifying cocrystal purity.
- Sample preparation and handling significantly impact the accuracy and reliability of the PXRD method.
- Increased methanol amounts in LAG enhanced IND-SAC cocrystal crystallinity.
Related Concept Videos
Determination of Crystal Structures
In the late 1800s, the revelation that light extended beyond visible wavelengths led to the discovery of X-rays by Wilhelm Roentgen. Recognized as high-energy electromagnetic radiation with short wavelengths, X-rays prompted exploration into their interaction with crystals. Max von Laue proposed in 1912 that the periodic arrangement of atoms, ions, or molecules in crystals would cause them to diffract X-rays, a hypothesis confirmed through experiments with copper sulfate and zinc sulfide...
X-ray Diffraction of Biological Samples
X-ray diffraction or XRD is an analytical tool that utilizes X-rays to study ordered structures such as crystalline organic and inorganic samples, polycrystalline materials, proteins, carbohydrates, and drugs.
According to Bragg's law, when X-rays strike the sample positioned on a stage, the rays are scattered by the electron clouds around the sample atoms. The X-ray diffraction or scattering is caused by constructive interference of the X-ray waves that reflect off the internal crystal...
According to Bragg's law, when X-rays strike the sample positioned on a stage, the rays are scattered by the electron clouds around the sample atoms. The X-ray diffraction or scattering is caused by constructive interference of the X-ray waves that reflect off the internal crystal...
X-ray Crystallography
The size of the unit cell and the arrangement of atoms in a crystal may be determined from measurements of the diffraction of X-rays by the crystal, termed X-ray crystallography.
Diffraction
Diffraction is the change in the direction of travel experienced by an electromagnetic wave when it encounters a physical barrier whose dimensions are comparable to those of the wavelength of the light. X-rays are electromagnetic radiation with wavelengths about as long as the distance between neighboring...
Diffraction
Diffraction is the change in the direction of travel experienced by an electromagnetic wave when it encounters a physical barrier whose dimensions are comparable to those of the wavelength of the light. X-rays are electromagnetic radiation with wavelengths about as long as the distance between neighboring...
Recrystallization: Solid–Solution Equilibria
Recrystallization is a purification technique used to separate impurities from solid compounds. In this technique, no chemical reactions occur. Instead, it exploits physical properties only, specifically, the solubility differences between the desired compound and impurities, either at a single temperature or at different temperatures, and under other selected conditions. The solid-solution equilibrium (solubility equilibrium) of each component in the solution represents a binary phase...

