Advertisement

Scanning Electron Microscopy and Energy-Dispersive X-Ray Spectrometry

  • Robert Allen Carlton
Chapter

Abstract

The scanning electron microscope (SEM) is used extensively in pharmaceutical development for both drug substance (DS) and drug product (DP). The vast bulk of the work is examination of size and shape of the individual particles making up the drug substance powder. Some of this work is quantitative in the sense that the size and shape of the particles are measured using image analysis (see Chaps. 7 and 9), but most of the work is more qualitative in nature. It is somewhat amazing that the SEM produces images that are readily interpreted by our visual system when you consider we are looking at the interaction of electrons with matter and that, in fact, there is no true optical system to the SEM. Even without numbers, one can get a sense of how the DS powder will behave based just on the appearance of the particles. If well-crystallized with sharp crystal edges, we may suppose the material will flow well. If it is highly agglomerated, with what appear to be particles fused together, we might suppose the powder will not flow as well. Even if those initial suppositions are somewhat naïve and general, just having an image of the particles can help workers understand the system they are dealing with. By the way, it is a rare technical presentation on drug substance that does not include at least one SEM image.

Keywords

Atomic Number Secondary Electron Backscatter Electron Pharmaceutical Development Secondary Electron Detector 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Bilde-Soerenson JB and Appel CC (1997) X-Ray Spectrometry In ESEM And LVSEM: Corrections For Beam Skirt Effects. In: Extended Abstracts of the 49th Annual Meeting of the Scandinavian Society for Electron Microscopy, Tholen AR (ed.) Svenski i Goteburg AB, Sweden, 12–15Google Scholar
  2. Carlton RA (1997) The Effect Of Some Instrument Operating Conditions On The X-Ray Microanalysis Of Particles In The Environmental Scanning Electron Microscope. Scanning 19:85–91CrossRefGoogle Scholar
  3. Carlton RA (1999) Energy Dispersive X-ray Spectrometry in the Environmental Scanning Electron Microscope, Microscope 47:1:5–11Google Scholar
  4. Carlton RA (2000) Quantitative X-ray Spectrometry Using the Environmental Scanning Electron Microscope. Dissertation, Lehigh UniversityGoogle Scholar
  5. Carlton RA (2009) Comparison of SiLi and SDD Detectors for Pharmaceutical Applications. Micros. Microanal 15:382–3CrossRefGoogle Scholar
  6. Carlton RA, Lyman CE, Roberts JE (2004) Charge neutralization in the ESEM for quantitative X-ray microanalysis. Micros. Microanal. 10(6):753–763Google Scholar
  7. Danilatos GD (1988) Foundations Of Environmental Scanning Electron Microscopy. In: Advances in Electronics and Electron Physics, Academic Press, Inc., 71:109–250Google Scholar
  8. Danilatos GD (1990a) A Gaseous Detector Device in the ESEM. In: Advances in Electronics and Electron Physics, Academic Press, Inc., 78:1–102Google Scholar
  9. Danilatos GD (1990b) Mechanisms of Detection and Imaging in the ESEM. J of Microscopy 160, Pt 1:9–19.Google Scholar
  10. Danilatos GD (1993) Introduction To The ESEM Instrument. Microscopy Research and Technique 25:354–361CrossRefGoogle Scholar
  11. Doehne E, Bower NW (1993) Empirical Evaluation Of The Electron Skirt In The Environmental SEM: Implications For Energy Dispersive X-Ray Analysis. Microbeam Analysis 2:S35–36Google Scholar
  12. Doehne, E (1997) A New Correction Method For High-Resolution Energy-Dispersive X-Ray Analyses In The Environmental Scanning Electron Microscope. Scanning 19:75–78.CrossRefGoogle Scholar
  13. Gauvin R (1999) Some Theoretical Considerations on X-ray Microanalysis in the Environmental or Variable Pressure Scanning Electron Microscope. Scanning 21:388-393.CrossRefGoogle Scholar
  14. Goldstein JI, Newbury DE, Echlin P, Joy DC, Lyman CE, Echlin P, Lifshin E, Sawyer L, Michael J (2003) Scanning Electron Microscopy and X-ray Microanalysis. 3rd Ed, Springer, New York, NYGoogle Scholar
  15. Griffin BJ, Nockolds CE (1996) Quantitative EDS Analysis in the Environmental Scanning Electron Microscope (ESEM) Using a Bremstrahlung Intensity-Based Correction for Primary Beam Variation and Scatter. Proceedings of the Annual Microscopy Society of America and the Microbeam Analysis Society. Bailey GW (ed.) San Francisco: San Francisco Press: 842–3Google Scholar
  16. Lifshin E, Doganaksoy N, Sirois J, Gauvin R (1999) Statistical Considerations in Microanalysis by Energy Dispersive Spectrometry. Microsc. Microanal. 4:598–604Google Scholar
  17. Lyman CE, Newbury DE, Goldstein JI, Williams DB, Romig AD, Armstrong JT, Echlin P, Fiori CE, Joy DC, Lifshin E, Peters KR (1990) Scanning Electron Microscopy, X-Ray Microanalysis, and Analytical Electron Microscopy: A Laboratory Workbook. Plenum Press, New YorkGoogle Scholar
  18. Newbury DE (1999) Standardless Quantitative Electron Excited X-ray Microanalysis by Energy-Dispersive Spectrometry: What is its Proper Role?. Micros. Microanal. 4:585-597Google Scholar
  19. Reimer L (1998) Scanning Electron Microscopy: Physics of Image Formation and Microanalysis. 2nd Ed. Springer-Verlag, BerlinGoogle Scholar
  20. Statham PJ (1978) Measurement And Use Of Peak-To-Background Ratios In X-Ray Analysis. Mikrochimica Acta [Wien]. Suppl.8:229–242.Google Scholar
  21. Ziebold TO (1967) Precision And Sensitivity In Electron Microprobe Analysis. Anal Chem 36:8:858–861.CrossRefGoogle Scholar

Internet References

  1. Clemex Technologies. http://www.clemex.com/
  2. Ritchie N, NIST Desktop Spectrum Analyzer II. http://www.cstl.nist.gov/div837/837.02/epq/dtsa2/index.html

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.GlaxoSmithKline Pharmaceuticals Physical PropertiesKing of PrussiaUSA

Personalised recommendations