Measuring the size of nanomaterials is a critical step in developing safe and effective drug products in modern nanomedicine. Dynamic light scattering (DLS) is the most commonly used technique for this purpose in pharmaceutical industry due to its simplicity.
It has, however, low resolution (if the product contains two size populations, such as 50 and 100 nm, it will wrongly detect only one population) and it may significantly overestimate the average size as larger particles scatter light with higher intensity.
Ardena has in-house an orthogonal advanced technique to overcome these limitations, the asymmetric flow field-flow fractionation (AF4) coupled online to multiple detectors, including DLS. AF4 – DLS overcomes the limitations of stand-alone DLS as the sample is first separated into distinct size populations and then measured. It is a broadly applicable to various types of nanoparticles (such lipid and metal nanoparticles) and is very accurate and reproducible for sizes up to approximately 100 nm.
To maintain accuracy when particle sizes exceed 100 nm, an advanced detection is required that overcomes artifacts of conventional online DLS.
In our latest research published in the Journal of Chromatography A, Maria Marioli and her team explored how to overcome these analytical hurdles.
The Solution: Advanced Detection in Nanomedicine
The study demonstrates that by coupling Asymmetric Flow Field-Flow Fractionation (AF4) with Phase and Spatially-Resolved Dynamic Light Scattering (PhaSR-DLS), specifically the NanoFlowSizer, analytical teams can eliminate the following artifacts of conventional AF4 – DLS which mainly occur for particle sizes above 100 nm:
– Size underestimation due to the flow through the detector.
– Inconsistent data due to low particle concentrations.
The findings of this study show that AF4 – PhaSR-DLS method fundamentally avoids these artifacts, regardless of experimental conditions.
Why This Matters in drug product development
For nanomedicines, accurate nanoparticle characterization is essential for successful drug development. Inaccurate size measurements may lead to wrong conclusions regarding filterability during manufacturing, bioavailability (cellular uptake), batch-to-batch consistency and product stability. By removing these measurement biases, we provide more reliable data, helping to de-risk drug development and ensure consistency from the lab to manufacturing.
This work underscores the importance of understanding and addressing limitations in conventional and modern analytical workflows, ensuring that critical quality attributes are monitored with the highest possible precision and accuracy.
“This article reflects our dedication to developing reliable methods for nanoparticle size determination, which is critical in drug product development.”– Maria Marioli , Principal Scientist at Ardena
Learn More
● Read the original research in the Journal of Chromatography A
