Lipid nanocapsule size analysis by hydrodynamic chromatography and photon correlation spectroscopy.

Particle size and the size distribution are known to be important factors in the overall behavior of nanoparticulate drug delivery systems and an exact determination of these parameters is highly important. Several techniques are applied in the size determination of nanoparticulates, particularly dynamic light scattering. Also other methods have been proposed, among them hydrodynamic chromatography (HDC). In order to characterize a HDC method for nanosized carriers, differently sized lipid nanocapsules having a diameter of 25-100 nm were analyzed and results were compared with measurements from photon correlation spectroscopy (PCS) and atomic force microscopy. Results from atomic force microscopy studies were generally not in line with determinations from the other techniques due to a particle shape loss by the drying step. PCS and HDC led to comparable results in simple size determination of lipid nanocapsules. However, slight differences were found during the characterization of more complex samples. HDC was able to detect micelles as a byproduct of nanocapsule preparation while in PCS the sample dilution turned micelles undetectable. HDC analysis was able to characterize mixed samples of particle batches differing in their average size similar to PCS. HDC was found to be an excellent tool for the determination of size and average size distribution of lipid nanocapsules.