Nicotine-loaded chitosan nanoparticles for dry powder inhaler (DPI) formulations – Impact of nanoparticle surface charge on powder aerosolization

Abstract

The aim of this study is to demonstrate the role of surface charge of nicotine loaded or unloaded chitosan (CS) nanoparticles on the dispersibility from dry powder inhaler (DPI) formulations. The nanoparticles were prepared using glutaraldehyde crosslinking of the amino groups of chitosan in a water-in-oil emulsion. Using dynamic light scattering (DLS) the particle size, size distribution and the zeta potential of nanoparticles were measured. The morphological characteristics were studied using SEM. The fine particle fractions (FPFs) of nanoparticles were determined by a twin stage impinger (TSI) using a Rotahaler at 60 L/min flow rate. The FPF of nanoparticles could be correlated to the surface charge i.e., FPFs were increased with increasing surface charge, which reduced with increased concentration of the drug. The FPF from the large carrier (lactose) based formulations was significantly higher (p < 0.001) than those of formulations without carriers. The higher FPF from the large carrier-based formulations was independent of zeta potential and thought to be associated with high impaction. These results suggested the mechanism of nicotine loaded CS nanoparticle dispersion without large carriers was dependent on the zeta potential, which was linked to the agglomeration or deagglomeration behaviour of particles.