Using an X-Ray Diffractometer in Transmission Mode for an XRD Investigation of Ibuprofen

X-ray diffraction is an established method used in the investigation of pharmaceutical mixtures and formulations, in both academic research and manufacturing contexts. Alongside a growing societal requirement for cutting edge drugs, there is also an increasing need for adaptable X-ray diffractometers to facilitate pharmaceutical studies.

Active pharmaceutical ingredients (APIs) and other compounds are obliged to meet demanding screening criteria such as salt formation, co-crystallization or polymorphism during research and production quality control. These steps can be conveniently satisfied with the assistance of powder X-ray diffraction, due to its intrinsic sensitivity and capacity to distinguish between divergent crystallographic structures.

There is also scope to undertake dynamic studies, and assess the crystallization behavior of compounds in various solvents and non-ambient conditions. Furthermore, the routine interpretation of the crystal arrangement of new compounds from powder data is now attainable. Additionally, X-ray diffraction even permits the researcher to monitor contamination during synthesis, which can vastly enhance processes.

Instrument

The Thermo Scientific™ ARL™ EQUINOX Series constitutes a portfolio of XRD instruments, ranging from straightforward, user-friendly bench-top systems for everyday analysis, to more sophisticated floor-standing, high-performance research level setups. The Thermo Scientific™ ARL™ EQUINOX 100 engages a bespoke 50 W Cu or 15 W Co high-brilliance micro-focus tube supported by mirror optics.

As a result of the low wattage demands, the instrument does not require an external water chiller. This makes the unit highly portable, and enables it to be transported between laboratories or into the field, and negates the need for any specific infrastructure.

The ARL EQUINOX 100 offers extremely rapid data acquisition rates in comparison to competing diffractometers because of its distinctive curved position sensitive detector (CPS). This calculates all diffraction peaks concurrently, and in real time, and is consequently ideally suited for transmission mode calculations (cf. Figure 1).

ARL EQUINOX 100 diffraction system

Figure 1. ARL EQUINOX 100 diffraction system

Experimental

Ibuprofen samples from four alternative providers were crushed and packed into transmission measurement cups with the use of scotch tape. Each sample was turned and computed for ten minutes utilizing Cu-Kα radiation (1.541874 Å). Data processing and assessment was undertaken using MATCH! E, which is reinforced by the COD database for qualitative phase analysis.

ARL EQUINOX 100 in transmission measurement mode

Figure 2. ARL EQUINOX 100 in transmission measurement mode

Results

Ibuprofen commodities (200 mg), both branded and unbranded, typically include an assortment of non-API compounds which usually diverge between providers. Those comprise cellulose, pigment or filming agents. XRD is the perfect methodology to explicitly differentiate between crystalline phases in such compounds.

Diffraction pattern (4 - 50°2θ) from four vendors (patterns are shifted vertically for better comparison)

Figure 3. Diffraction pattern (4 - 50° 2θ) from four vendors (patterns are shifted vertically for better comparison)

The four samples from different providers, exhibiting divergent formulations (peak positions are represented as vertical lines), are presented below. The evidence of the different products clearly demonstrates differing diffraction patterns (cf. Figure 3). The market contains numerous generic products, of which one was examined, revealing Ibuprofen as the sole crystalline phase (cf. Figure 4). These results are similar to one branded product, of which only traces of talc (green, implemented as a lubricant) are observable (cf. Figure 5).

Diffraction pattern (4 - 50°2θ) of generic product

Figure 4. Diffraction pattern (4 - 50° 2θ) of generic product

Diffraction pattern (4 - 50°2θ) Brand Product 1

Figure 5. Diffraction pattern (4 - 50° 2θ) Brand Product 1

Apart from these two instances, there are providers who utilize additives (additionally to talc) to achieve alternative specifications (cf. Figure 6). Among these, Brand Product 3 is contrasted with Brand Product 2, the latter of which includes Sodium Citrate (purple) but contains no Calcite (grey) (arrows represent divergences).

Diffraction pattern (4 - 50°2θ) Brand Products 2 and 3

Figure 6. Diffraction pattern (4 - 50° 2θ) Brand Products 2 and 3

Sodium Citrate and Calcium Carbonate are employed as buffering agents to reduce the stomach damage that Ibuprofen generates, while Sucrose (blue) offers a more agreeable flavor.

Conclusion

The favorable resolution of the ARL EQUINOX 100 in transmission mode geometry permits the user to explicitly reconcile the crystalline phases in divergent pharmaceutical compounds. A ten minute calculation time is all that is required to undertake a qualitative phase analysis, and concurrently enables the detection of trace phases.

Therefore, the ARL EQUINOX 100 represents an efficient, user-friendly instrument that can be used in all sectors of pharmaceutical research or production, ranging from preformulation to QA/QC of the consequent pharmaceutical commodity.

This information has been sourced, reviewed and adapted from materials provided by Thermo Fisher Scientific - Elemental Analyzers.

For more information on this source, please visit Thermo Fisher Scientific - Elemental Analyzers.

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