Production of Highly Charged Pharmaceutical Aerosols Using a New Aerosol Induction Charger

Abstract

Purpose: Properly charged particles can be used for effective lung targeting of pharmaceutical aerosols. The objective of this study was to characterize the performance of a new induction charger that operates with a mesh nebulizer for the production of highly charged submicrometer aerosols to bypass the mouth-throat and deliver clinically relevant doses of medications to the lungs.

Methods: Variables of interest included combinations of model drug (albuterol sulfate) and charging excipient (NaCl) as well as strength of the charging field (1-5 kV/cm). Aerosol charge and size were measured using a modified electrical low pressure impactor system combined with high performance liquid chromatography.

Results: At the approximate mass median aerodynamic diameter (MMAD) of the aerosol (~0.4 μm), the induction charge on the particles was an order of magnitude above the field and diffusion charge limit. The nebulization rate was 439.3 ± 42.9 μl/min, which with a 0.1% w/v solution delivered 419.5 ± 34.2 μg of medication per minute. A new correlation was developed to predict particle charge produced by the induction charger.

Conclusions: The combination of the aerosol induction charger and predictive correlations will allow for the practical generation and control of charged submicrometer aerosols for targeting deposition within the lungs.

Figure 1

The induction charger device which connects the vibrating mesh nebulizer to the flow stream, positions the counter electrode below the mesh, and accelerates the airflow in the vicinity of the charging field.

Figure 2

An example of (a) current profiles vs. time on the ELPI electrometers, (b) total cumulative charge for each ELPI stage, and (c) collected mass on each stage, for a 60 second nebulization of 0.05% AS at a 5kV charging voltage.

Figure 2

An example of (a) current profiles vs. time on the ELPI electrometers, (b) total cumulative charge for each ELPI stage, and (c) collected mass on each stage, for a 60 second nebulization of 0.05% AS at a 5kV charging voltage.

Figure 2

An example of (a) current profiles vs. time on the ELPI electrometers, (b) total cumulative charge for each ELPI stage, and (c) collected mass on each stage, for a 60 second nebulization of 0.05% AS at a 5kV charging voltage.

Figure 3

Effect of charging voltage on the number of elementary units of charge acquired by each particle on Stage 6, with an aerodynamic cut size of 0.39 μm for different solutions. The coefficient of determination is equal to one (R²=1) for the four linear fits.

Figure 4

Number of elementary units of charge per particle (Q_p) acquired for different aerodynamic diameters collected on Stages 3–8 of the ELPI at 5 kV using different nebulized solutions.

Figure 5

Total and specific charge on Stage 6 (cut size 0.39 μm), which had the maximum charge and mass, for the four nebulized solutions and charging with 5kV. The total charge for 0.1% was significantly different from 0.05% AS (* Tukey HSD, p<0.05). No other significant differences were observed.

Figure 6

Comparison of the measured induced number of elementary charges on the surface of the dried particles (blue squares) with the predicted values based on the theory of Reischl et al. applied to the diameter of dried particles (red circles) and initial droplet diameter prior to evaporation (black diamonds).

Figure 7

Correlation for induced elementary charges per particle in terms of charging voltage (V in kV), final aerodynamic diameter (d_a in μm) and conductivity (σ in μS/cm) compared with the experimental values.