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Imaging directed Raman spectroscopy and laser diffraction make a powerful combination

17 February 2011 No Comment

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As Product Marketing Manager at Malvern Instruments my responsibilities cover both laser diffraction and analytical imaging systems, so I am delighted to have been asked to contribute this  blog post, the third in our series on ‘Linking Technologies’. The subject for today is the complementary application of automated image analysis combined with Raman Spectroscopy, and  laser diffraction particle size analysis. In my opinion, a combination of techniques that has the potential to create significant advantage in pharmaceutical analysis.

Know your techniques, fit them to your needs

Laser diffraction and automated imaging have very different attributes. Understanding these relative strengths is the key to using them appropriately and productively, together.

Laser diffraction is incredibly fast, with measurement times of just seconds. It delivers real-time data and can be installed on-line for routine process analysis during manufacture, but it can only characterise the whole formulation, providing no compositional differentiation.

Compared with manual microscopy, automated imaging is fast, but measurement times are still in the order of minutes. However, for this extra expenditure of time you get size and shape data, additional information that can be extremely valuable during development or when solving a tricky troubleshooting problem.

Now with the introduction of imaging systems that include Raman spectroscopy we can probe our particles even further. We can look at size, shape and composition and how all three interconnect.

Morphologically directed Raman spectroscopy


Morphologically directed Raman (MDR) spectroscopy using the Morphologi G3-ID compares the Raman spectra of individual particles(left – blue headers) with reference spectra (left – green headers) which can then be related back to actual images of the relevant specimens (right).

With the addition of a Raman microprobe and spectrometer to an automated imaging system, the Morphologi G3-ID can now identify chemical differences between particles, sort the active pharmaceutical ingredient (API) from excipients, and enable visual and analytical comparison of the size and shape of constituent ingredients. Anyone interested in Malvern’s early access program for this exciting new system should contact us directly.

By using imaging data to target the acquisition of Raman spectra – so called Morphologically Directed Raman (MDR) spectroscopy – the time for measurements can be significantly reduced compared to standard Raman mapping methods. In addition, the measurement set up is simplified compared to standard methods, as the position of the particles is automatically determined prior to analysis, removing any operator subjectivity.

What can be achieved for nasal sprays

The characterization of nasal sprays offers a particularly good example of what can be achieved by applying both laser diffraction and MDR spectroscopy directed imaging.

First laser diffraction is used to look at the formulation as a whole, in real-time. This provides data describing spray dynamics towards  development of the performance of both formulation and device. Then imaging is used to look at how the active copes with the dispersion process – with Raman we can reliably differentiate the active even if it’s the same shape as any excipient present. We can then make sure size and shape remain the same, both pre- and post-dispersion.

For all those involved in the development of drug inhalation formulations and devices, including nasal sprays, I would therefore recommend they read the full case study demonstrating the benefits of combining laser diffraction measurements with MDR spectroscopy, and/or watch the on-demand ‘Early access to the Morphologi G3-ID’ webinar.

Widening the net

In such a competitive environment as the pharma industry, any advantage can make the difference between success and failure. I have a feeling that efficiency will remain a well used word over the coming decade and anything that can make either post-development QC, formulation development, or formulation/device assessment, better has the potential to make a difference.

Of course, although we developed this new system with the pharmaceutical industry in mind, I know from my experience of introducing new analytical tools to market that there is likely to be multiple other applications that we haven’t yet thought of. If you believe MDR spectroscopy, either combined with laser diffraction or as a stand alone technique, might benefit your field of science  we would love to hear from you!