Evaluation of a Nanodispersion Formulation Prepared through Microfluidic Reactors for Pulmonary Delivery of Budesonide Using Nebulizers

摘要

This study aimed to determine the aerosolization behavior of a nanodispersion of budesonide, prepared using microfluidic reactors. The size and morphology of budesonide nanoparticles were characterized by photon correlation spectroscopy (PCS) and transmission electron microscopy (TEM). Processing/formulation parameters for formation of the nanoparticles were studied to determine their effects on the particle size. Results showed a narrow distribution for budesonide nanodispersion with spherical and smooth surfaced particles. To investigate the in-vitro aerosolization performance of the nanodispersion, the preparation was compared with a commercially available budesonide microsuspension using the Comité Européen Normalization (CEN) methodology. Aerosolization results showed that the fine particle fraction (FPF) generated from the budesonide nanodispersion was significantly higher than that of the marketed budesonide (ie. mean (SD) 56.88 (3.37)% vs. 38.04 (7.82)%, respectively). Additionally, mass median aerodynamic diameter (MMAD) of nano-budesonide dispersion was significantly smaller than the microsuspension (ie. mean (SD) 3.91 (0.49) vs. 6.22 (1.09) μm, respectively), with nebulization time of nano-budesonide dispersion significantly shorter than the marketed budesonide microsuspension (ie. 12.3 (0.37) vs. 14.85 (0.36) min, respectively). The produced nanodispersion was found to be stable over a period of 10 days if stored at 4 °C.