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

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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.

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Abbreviations

AS:

Albuterol sulfate

c i :

Thermal speed of the ions (240 m/s at 293°K)

D :

Droplet diameter

d a :

Aerodynamic diameter

D p :

The diameter of residual solid particle in Reischl’s correlation (Eq. 6)

E :

Electric field

e :

Charge of an electron or elementary charge unit (e = 1.6 × 10−19 C)

ELPI:

Electrical Low Pressure Impactor

GSD:

Geometric standard deviation

H :

Induction electrode to orifice plate gap distance

HPLC:

High performance liquid chromatography

i :

The number of recorded ELPI data points (1–60 given the default 1 s sampling time used by the ELPI and 60 s nebulization)

I i :

The current measured at time i for each stage

I i+1 :

The current measured at time i + 1 for each stage

I stage :

Total current recorded for each stage

K :

Relative concentration of solution in Reischl’s correlation (ratio of volume of solute to total volume)

L :

Droplet to orifice distance at the instant of droplet separation

m AS :

Measured mass of AS on each impactor stage

m f AS :

Nominal mass fraction of albuterol sulfate

m f NaCI :

Mass fraction of sodium chloride

MMAD:

Mass median aerodynamic diameter

m solute :

Total mass of deposited solute (i.e. drug and excipient)

N i :

The concentration of ions

Q :

Number of elementary charges on the droplet

Q/m :

Specific charge (charge to mass ratio of the ELPI’s stage)

Q 0 :

Number of elementary charges on the droplet by spraying process

Q p :

Number of elementary charges per particle

q stage :

Total charge on each impactor stage

t i :

The time of data point number i

t i+1 :

The time of data point number i + 1

V :

Charging voltage

Z i :

Mobility of ions

ρ AS :

Density of albuterol sulfate (1.350 g/cm3)

ρ NaCI :

Density of sodium chloride (2.165 g/cm3)

ρ particle :

Density of the multicomponent particle

α :

Correction factor to account for the nonuniformity of the electric field

β:

Induction charging coefficient in Reischl’s correlation (elementary charges per charging voltage Eq. 5)

ε :

Relative permittivity (dielectric constant)

σ :

Conductivity of solution (μS/cm)

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ACKNOWLEDGMENTS AND DISCLOSURES

Research reported in this publication was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health under Award Number R21HD073728. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, Virginia, USA

    Laleh Golshahi, P. Worth Longest & Landon Holbrook

  2. Department of Pharmaceutics, Virginia Commonwealth University, Richmond, Virginia, USA

    P. Worth Longest, Jessica Snead & Michael Hindle

Authors
  1. Laleh Golshahi
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  2. P. Worth Longest
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  3. Landon Holbrook
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  4. Jessica Snead
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  5. Michael Hindle
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Correspondence to Laleh Golshahi.

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Golshahi, L., Longest, P.W., Holbrook, L. et al. Production of Highly Charged Pharmaceutical Aerosols Using a New Aerosol Induction Charger. Pharm Res 32, 3007–3017 (2015). https://doi.org/10.1007/s11095-015-1682-6

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  • DOI: https://doi.org/10.1007/s11095-015-1682-6

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