Research paperNicotine hydrogen tartrate loaded chitosan nanoparticles: Formulation, characterization and in vitro delivery from dry powder inhaler formulation

This study reports the development of nanoparticles in the form of inhalable micro-aggregates of biodegradable chitosan (CS) loaded with nicotine hydrogen tartrate (NHT) for potential pulmonary delivery of nicotine from dry powder inhaler (DPI) formulations with prolonged release profile. The NHT-loaded CS particles were prepared using a water-in-oil emulsion crosslinking method. The prepared particles were characterized using scanning electron microscopy (SEM) and transmission electron microscopy (TEM) for morphological studies; Zetasizer and Mastersizer were applied for particle size analysis. The in vitro aerosolization of the formulations was studied using a twin-stage-impinger (TSI) and promising aerosolization characteristics were shown. The nanoparticles were spherical with size ranges between 167 and 411 nm while micro-aggregates (3.73-4.73 μm) were formed among nanoparticles. According to differential scanning calorimetry (DSC), X-ray diffraction (XRD) analysis and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, the NHT crystallinity was lost when in the particles, indicating it was uniformly dispersed as a solid solution. On the basis of X-ray photoelectron spectroscopy (XPS) analysis, the amount of NHT loaded on the surface of CS increased proportionally with increasing drug loading in the bulk so there was no surface enhancement. The fine particle doses (FPD) of NHT ranging between 1.7 and 3.2 mg from DPI formulations were concentration dependent and increased with increased drug loading. Based on the in vitro release study, NHT released from CS particles with a burst release in the first 8 h and subsequent prolonged release of nicotine.

TEM images of unloaded (blank CS; A) and NHT-loaded (B) chitosan nanoparticles and their dispersibility.91