Boosting the aerodynamic properties of vibrating-mesh nebulized polymeric nanosuspensions

Pulmonary application of drug-loaded polymeric nanosuspensions is achieved by vibrating-mesh nebulizers, which allow for an output of intact nanocarriers from the nebulizer reservoir. However, adequate aerosol droplet sizes are a prerequisite for an efficient pulmonary deposition. The current study discloses experimental findings useful to optimize the aerodynamic characteristics of formulations atomized by the vibrating-mesh nebulizers Aeroneb(®) Pro and eFlow(®)rapid. Parameters with significant influence on the aerosol droplet diameter were identified by a statistical design analysis rating size results from laser diffraction. Subsequently, the effect of selected biocompatible solutes on the aerodynamic performance of nebulized formulations was studied and correlated with their physicochemical properties. Vibrating-mesh generated aerosols were significantly affected by the dynamic viscosity and conductivity of the applied formulation. Consequently, an increase in viscosity enhancer (sucrose and poly(ethylene glycol)) or electrolyte (NaCl and CaCl2) content caused the droplet diameter to decrease. Similarly, purified nanosuspensions revealed a considerable decline in aerosol particle size upon excipient addition. However, coating of polymeric nanoparticles with poloxamer and poly(vinyl alcohol) was necessary to avoid electrolyte-induced nanoparticle aggregation. Overall, the current study emphasizes that supplementation of nanosuspensions with biocompatible solutes is an excellent means to tailor the characteristics of aerosols generated by vibrating-mesh technology.