A detailed analysis of biodegradable nanospheres by different techniques--a combined approach to detect particle sizes and size distributions.

Poly(d,l-lactide-co-glycolide) nanosupensions as intravenous nanosphere systems were produced by solvent deposition in aqueous Poloxamer 188 solutions. Light scattering techniques were applied to these colloidal systems to characterize particle sizes. Regularly shaped spherical particles were received as proved by freeze fracture replica and small-angle X-ray scattering (SAXS). SAXS was performed using intensive synchrotron radiation. Particle sizes were calculated from the small-angle part of scattering curve that were in good agreement with z-average values received from photon correlation spectroscopy (PCS). The flow field-flow fractionation (FlFFF) fractograms in combination with multi-angle light scattering (MALS) allowed an easy detection of maximum particle sizes what is most important for parenteral systems. Furthermore, high quality size distributions were received due to the separation step prior to size characterization. The calculated average size values exhibited a good correlation with z-averages determined by PCS. Only for suspensions of broader size distributions, higher deviations were observed. Comparing particle sizes with and without Poloxamer, differences in diameters resulted that were quantified. The additional Poloxamer shell was not able to be removed by an intensive washing during FlFFF focusing and separation. Especially FlFFF/MALS proved to be a valuable tool to characterize the pharmaceutical nanosuspensions in detail what is of great importance especially for controlled drug delivery systems.