Hollow-fiber flow field-flow fractionation and multi-angle light scattering as a new analytical solution for quality control in pharmaceutical nanotechnology

The rapid development of nanoproducts in pharmaceutical field highlights the need for robust analytical methods to ensure their quality and stability. Nanoparticles of different nature and composition (NPs) are employed for many purposes, such as the improvement of drug solubility/bioavailability and the controlled delivery of drugs. Among NPs features, particle size distribution (PSD) plays a fundamental role in determining NPs properties. Nevertheless the high development of different NPs, authorities such as the FDA and the European Union highlight the lack of robust characterization methods and quality control for nanomaterials. Among the techniques for the size-characterization of particles, Field-Flow Fractionation (FFF) represents a competitive choice: due to the absence of a stationary phase, the separation mechanism is gentle with total maintenance of the native properties of the analytes. In this paper the microcolumn variant of FFF, the Hollow-Fiber Flow FFF (HF5), is coupled on-line with Multi-Angle Light Scattering (MALS) for the development of methods for the characterization of NPs as quality control in new pharmaceutical field. The HF5-MALS was applied to the size characterization in different preservation conditions of silver polyvinylpyrrolidone-stabilized NPs (AgPVP) used for their antimicrobial activity. The ratio of gyration and hydrodynamic radii of AgPVP was evaluated for fresh and aged NPs, suggesting in this case aggregation rearrangement. The influence of different PVP coating and dilution factor was also studied. Finally the metal ion release was determined in relationship to these shape modifications. The HF5-MALS method is robust and reproducible and it can be considered as an important tool for the development of analytical platform for quality control of NPs.