Sugar-cupBack in 2008 we published an article on dynamic light scattering (DLS) from sucrose solutions. This was quite a project, as we had previously seen the effect of ‘solvent peaks’ yet never thoroughly investigated these. In the article titled “Measuring sub nanometre sizes using dynamic light scattering” we showed that a peak below 1 nm was indeed due to the Brownian motion from sucrose molecules in solution, and then backed up the claim with supporting evidence. What we had stumbled across but were not quite able to explain was a recurring peak in the 100-200nm region that just would not disappear, even upon filtration through 20nm Anotops.

Well, our customers seems to have now gone to the bottom of that mystery: in “Nanoparticulate Impurities in Pharmaceutical-Grade Sugars and their Interference with Light Scattering-Based Analysis of Protein Formulations” the authors (Daniel Weinbuch, Jason K. Cheung, Jurgen Ketelaars, Vasco Filipe, Andrea Hawe, John den Engelsman, and Wim Jiskoot) used nanoparticle tracking analysis (NTA), and backed up their results with fourier transform infrared (FTIR) microscopy, scanning electron microscopy coupled energy dispersive X-ray spectroscopy (SEM-EDX), and fluorescence (FL) spectroscopy. They conclude that the nanoparticles in sucrose solutions were agglomerates of various impurities (suspected to be high molecular weight dextranes and cross-linked dextranes by FTIR) originating from the raw material and production process. The various sources of sugar showed nanoparticles in the 100-200nm range of up to 10^9 nanoparticles per g. It’s interesting to note that the various sources showed quite large differences, and that their most careful sample preparation involved diafiltration through molecular weight cutoff membranes. In their hands, even 20nm filtration eliminated the nanoparticle peak.

What does this mean for pharmaceutical formulations? Sugars such as sucrose, trehalose, fructose, maltose, galactose, etc are often used as additives, thus in order to fully observe whether protein aggregates are present, the buffer should be analyzed on its own, or possibly filtered to subtract the inherent sugar nanoparticles present.Sugar-infographic

On an entirely different practical note: Annual sucrose consumption on average is 24 kg per person of all ages in the world. These 65g of sugar per day translate into about 10^10 nanoparticles each of us digests every day and that’s just from sugar.

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