Analysis of pharmaceutical materials using secondary electron hyperspectral imaging

Session

Poster Session Two

Authors

Stuart Micklethwaite (2), Rastra Basnet (2), Joseph Ma (2), James Nohl (1), Dr Nicholas Farr (1), Professor Cornelia Rodenburg (1), Dr Nicole Hondow (2)

Affiliations

1. Department of Materials Science and Engineering, The University of Sheffield
2. Leeds Electron Microscopy and Spectroscopy Centre, School of Chemical and Process Engineering and the Bragg Centre for Materials Research, University of Leeds

Keywords

SEM

spectroscopy

SEHI

pharmaceutical materials

Abstract text

Secondary electron hyperspectral imaging (SEHI) is a recently developed novel technique that provides enhanced surface characterisation. Spectra sensitive to composition, chemical bonding and structure can be formed by collection of the secondary electrons that are emitted from a material following irradiation by an electron beam in the SEM. A variety of materials have been examined by SEHI, not limited to perovskites,¹ polymer blends and biomaterials,^2,3 and various carbon materials^4,5; however, the technique has not be applied to materials of pharmaceutical interest.

Pharmaceutical materials are often complex mixtures, containing multiple organic and possibly inorganic components. A coating can increase the stability and longevity of tablets, and this is evident in many commercially available pain relief medications. In this work, a commercially available pain relief tablet and related reference materials are examined to assess the suitability of SEHI for the further analysis of pharmaceutical materials.

SEM images and SEHI were collected using an FEI Helios G4 CX, a dual beam scanning electron microscope. The hyperspectral images were collected using a monochromated 1 kV accelerating voltage, a typical vacuum pressure of 10^-6 mbar, and a range of probe currents. Complimentary EDX spectroscopy has been undertaken using an Oxford Instruments 150 mm² EDX detector. An example commercially available pain relief tablet, Nurofen Plus, has been examined, in addition to reference materials ibuprofen, anatase and rutile. Samples have been prepared by both embedding in Field’s metal and by FIB-prepared lamellae.

Sample preparation is a particular challenge in this work, with the non-conductive pharmaceutical samples charging which causes anomalous features in the produced secondary electron spectra.  Comparison of various sample preparation methods, each with advantages and disadvantages will be presented, with guidance from previous work with sample preparation of powder materials utilised.⁶ The chosen commercially available pain relief tablet has a coating containing an inorganic pigment (TiO₂) which has led to the analysis of different structures, anatase and rutile. The applicability of SEHI to the damage and integrity of the coatings is examined, assessing this technique for the nanoscale characterisation of these formulated products.

In conclusion, this work will present the first analysis of pharmaceutical materials by secondary electron hyperspectral imaging. The advantages and challenges associated with this technique when applied to these materials will be detailed.

 

Acknowledgements

This work was funded by the EPSRC grant See More Make More: Secondary Electron Energy Measurement Optimised for Reliable Manufacture of Key Materials: Opportunity, Realisation, Exploitation in Leeds (EP/V011995/1) and Sheffield (EP/V012126/1). Instrumentation was funded by the EPSRC grant EP/P00122X/1.

References

1. V. Kumar et al, ACS Omega 2017, 2, 2126.
2. R. Masters et al, Nature Communications 2015, 6, 6928.
3. N. Farr et al, Macromolecular Rapid Communications 2020, 41, 1900484.
4. K. Abrams et al, Advanced Science 2019, 6, 1900719.
5. N. Farr et al, Polymer Chemistry 2021, 12, 177.
6. J. Nohl et al, Micron 156, 2022, 156, 103234.