4.3.1. Powder X-ray Diffraction (PXRD)

PXRD is a non-destructive analytical technique used for the measurement of crystalline and non-crystalline materials. It is utilized to collect structural data at the anatomic level to understand phase transitions, determine the degree of crystallinity, and identify polymorphic and solvatomorphic phases [90,91]. It is an essential tool in pharmaceutical research as it can be applied to polycrystalline materials in both solid and liquid forms. It has application in all stages of drug development, production, and quality control testing of API, excipients, and final products [90,91]. It is an easy-to-use technique, yields reliable and reproducible results and is relatively inexpensive. Moreover, it is highly sensitive and has applications in both qualitative and quantitative analyses [90].

PXRD is more difficult to use to determine the crystal morphology or habit of an API and excipients, and to investigate crystal morphology changes while these substances maintain crystallinity [92]. Peak broadening for particles below 3 nm in size coupled with non-suitability for amorphous materials are the main drawbacks of this technique [86]. In research conducted by Upadhyay et al., the PS of magnetite nanoparticles were determined using X-ray line broadening. The broadening of XRD peaks was mainly caused by particle/crystallite size and lattice strains other than instrumental broadening [93].

Similarly, Li et al. used XRD and noticed that after preparing copper telluride nanostructures with different shapes (i.e., cubes, plates, and rods), the relative intensities between the different XRD peaks varied in relation to the particle shape [94].

The XRD-derived size is often larger than magnetic size. This is due to smaller domains being present in a particle where all moments are aligned in the same direction, even if the particle is a single domain. Consequently, the use of microscopy is often preferred for size determination over XRD [95].
