The present research aims to characterize the particle size distribution of sub micron particles suspended in a liquid. The particles milled are an organic poorly water soluble crystalline product. To characterize the size of these particles, different techniques have been tested: imaging techniques (SEM, CryoTEM), static light scattering techniques, dynamic light scattering techniques, centrifugation and flow field flow fractionation.
The results indicate that the studied milled particles have a primary particle size close to 180nm and there is strong evidence of larger particles which are very likely aggregates. This is clearly seen from the Cryo TEM results.
All the above mentioned techniques should in principle be able to measure samples of dispersion containing particles of ca 180 nm but several are disturbed by the presence of large aggregates. It is difficult to estimate the amount of aggregate present, but most of the time one is interested in what the primary particle size distribution is.
It is clear that no single piece of equipment is capable of exactly determining the particle size distribution of our samples, but the static light scattering with low shear on mixing does give a good representation of what is seen with the image analysis by cryo TEM.