Particulate matter and, in general, contaminations from unknown sources, are a serious problem in
many industries. However, nowhere is this truer than in the manufacture of liquid dosage forms.
However, the unwanted degradation of active ingredients, as well as production and
packaging processes, can leave traces of particulate contamination in the product.
The uptake of these µ-particles via injections can put patients
at significant health risk. Pharmacopoeias are therefore very interested in identifying the
origin of any particles found in liquid dosage forms to prevent reoccurrence.
The USPs <788> and <787> recognize FT-IR µ-spectroscopy as a suitable tool for
the characterization of subvisible particulate matter in injectables,
such as therapeutic proteins or vaccines.
To demonstrate this kind of particle analysis using the LUMOS II FT-IR microscope,
we prepared a protein solution, which could be anything from antibodies to insulin.
As a first step, any particulate matter must be separated from the liquid phase. For this,
the sample was opened and filtered onto a 25 mm Anodisc (Al2O3) filter with 0.2 μm pore size.
When the particle loaded filter is dry, we mount it on the spring-loaded sample
holder and insert it into the LUMOS II to start the analysis.
The software, OPUS, is the analytical control center. We begin by capturing a visible image
of the sample’s region of interest. This could be any size, even the whole filter.
Next, we select the single point detector in transmission mode and use the „find
particle“ function. Particles on the filter are then detected based on the visual image.
This assigns an FT-IR measurement point to each
particle fully automatically. With one more click we then start the analysis.
The LUMOS will now approach each measurement point, adjust the aperture to match the particle,
and record an IR spectrum. Again, completely automated.
Then we take this data …
… match it to a spectral library to assess the identity …
… and are able to create comprehensive statistics.
But wait - even though this seems like an effective methodology at first glance,
there must be a smarter way to analyze micro particles
Let’s step back to detector selection for a moment.
What if we could put particle detection on a more powerful foundation than visual
contrast? We actually can - by using the focal plane array detector and by
creating a highly resolved chemical image in a matter of seconds.
Now, instead of selecting several single measurement points, we just target an
area to investigate. For this we place a measurement grid across the whole area.
By starting the analysis, the focal plane array collects 1024 FT-IR measurement points
at resolution of 5 µm with every scan. Already, we can see the particles popping up in bright colors.
But it's not just the measurement that's getting smarter, the evaluation is too. Applying Bruker's
ai-based adaptive chemical imaging will evaluate the complete sample area with a single click.
Autonomously classifying IR spectra, making it easy to
detect particulates or other contaminations.
In addition, we can also use the "Find Particle" function to create a list of
the particles, this time based on the FT-IR image.
Fortunately, this was just a trial sample created to
benchmark the LUMOS II - and not a real-life injectable solution.
In conclusion, the LUMOS II and its smart features make micro particle
analysis for injectable media faster, fully automated, and a lot easier.
Thanks for watching.