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Micrometer-Scale Particle Sizing by Laser Diffraction: Critical Impact of the Imaginary Component of Refractive Index

Pharmaceutical Research volume 22, pages 518–522 (2005)Cite this article

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Purpose.

This study evaluated the effect of the imaginary component of the refractive index on laser diffraction particle size data for pharmaceutical samples.

Methods.

Excipient particles 1–5 μm in diameter (irregular morphology) were measured by laser diffraction. Optical parameters were obtained and verified based on comparison of calculated vs. actual particle volume fraction.

Results.

Inappropriate imaginary components of the refractive index can lead to inaccurate results, including false peaks in the size distribution. For laser diffraction measurements, obtaining appropriate or “effective” imaginary components of the refractive index was not always straightforward. When the recommended criteria such as the concentration match and the fit of the scattering data gave similar results for very different calculated size distributions, a supplemental technique, microscopy with image analysis, was used to decide between the alternatives. Use of effective optical parameters produced a good match between laser diffraction data and microscopy/image analysis data.

Conclusions.

The imaginary component of the refractive index can have a major impact on particle size results calculated from laser diffraction data. When performed properly, laser diffraction and microscopy with image analysis can yield comparable results.

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Abbreviations

d(0.1):

particle diameter corresponding to 10% of the cumulative undersize volume distribution

d(0.5):

particle diameter corresponding to 50% of the cumulative undersize volume distribution (median particle diameter)

d(0.9):

particle diameter corresponding to 90% of the cumulative undersize volume distribution

IA:

microscopy with image analysis

kp:

imaginary component of the particle refractive index

LD:

laser diffraction

np:

real component of the particle refractive index

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Author information

Affiliations

  1. Department of Pharmaceutics, Amgen, Inc., Thousand Oaks, California, USA

    Alice Beekman, Daxian Shan, Alana Ali, Weiguo Dai & Merrill Goldenberg

  2. Malvern Instruments Ltd., Malvern, UK

    Stephen Ward-Smith

  3. Amgen, Inc., Thousand Oaks, California, USA

    Merrill Goldenberg

Authors
  1. Alice Beekman
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  2. Daxian Shan
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  3. Alana Ali
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  4. Weiguo Dai
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  5. Stephen Ward-Smith
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  6. Merrill Goldenberg
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Correspondence to Merrill Goldenberg.

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Beekman, A., Shan, D., Ali, A. et al. Micrometer-Scale Particle Sizing by Laser Diffraction: Critical Impact of the Imaginary Component of Refractive Index. Pharm Res 22, 518–522 (2005). https://doi.org/10.1007/s11095-005-2494-x

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  • DOI: https://doi.org/10.1007/s11095-005-2494-x

Key words:

  • image analysis
  • imaginary component of refractive index
  • laser diffraction
  • microscopy
  • particle size
  • refractive index