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Measuring The Bipolar Charge Distributions of Fine Particle Aerosol Clouds of Commercial PMDI Suspensions Using a Bipolar Next Generation Impactor (bp-NGI)

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Abstract

Purpose

To measure the charge to mass (Q/M) ratios of the impactor stage masses (ISM) from commercial Flixotide™ 250 μg Evohaler, containing fluticasone propionate (FP), Serevent™ 25 μg Evohaler, containing salmeterol xinafoate (SX), and a combination Seretide™ 250/25 μg (FP/SX) Evohaler metered dose inhalers (MDIs). Measurements were performed with a purpose built bipolar charge measurement apparatus (bp-NGI) based on an electrostatic precipitator, which was directly connected below Stage 2 of a Next Generation Impactor (NGI).

Methods

Five successive shots of the respective MDIs were actuated through the bp-NGI. The whole ISM doses were electrostatically precipitated to determine their negative, positive and net Q/m ratios.

Results

The ISM doses collected in the bp-NGI were shown to be equivalent to those collected in a standard NGI. FP particles, actuated from Flixotide™ and Seretide™ MDIs, exhibited greater quantities of negatively charged particles than positive. However, the Q/m ratios of the positively charged particles were greater in magnitude. SX particles from Serevent™ exhibited a greater quantity of positively charged particles whereas SX aerosol particles from Seretide™ exhibited a greater quantity of negatively charged particles. The Q/m ratio of the negatively charged SX particles in Serevent™ was greater in magnitude than the positively charged particles.

Conclusions

The bp-NGI was used to quantify the bipolar Q/m ratios of aerosol particles collected from the ISMs of commercial MDI products. The positive charge recorded for each of the three MDIs may have been enhanced by the presence of charged ice crystals formed from the propellant during the aerosolisation process.

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Abbreviations

API:

Active pharmaceutical ingredient

BNC:

Bayonet Neill-Concelman

BOLAR:

Bipolar charge analyser

bp-NGI:

Bipolar next generation impactor

DC:

Direct current

ED:

Emitted dose

ELPI:

Electrical low pressure impactor

ESPART:

Electrical single particle aerodynamic relaxation time

FP:

Fluticasone propionate

HFA:

Hydrofluroalkane

HPLC:

High performance liquid chromatography

ISM:

Impactor stage mass

NGI:

Next generation impactor

pMDI:

Pressurized metered dose inhaler

RD:

Recovered dose

SX:

Salmeterol xinafoate

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Authors and Affiliations

  1. Pharmaceutical Surface Science Research Group, Department of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, UK

    Martin Rowland, Jag Shur & Robert Price

  2. Pfizer Ltd, Discovery Park House, Sandwich, Kent, CT13 9NJ, UK

    Martin Rowland

  3. Novartis Pharma AG, Forum 1, Novartis Campus, 4056, Basel, CH, Switzerland

    Alessandro Cavecchi & Frank Thielmann

  4. Chiesi Farmaceutici S.p.A, Via Palermo, 26 A, 43122, Parma, Italy

    Alessandro Cavecchi

  5. Faculty of Computing, Engineering and Science, University of South Wales, Pontypridd, CF37 1DL, UK

    Janusz Kulon

Authors
  1. Martin Rowland
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  2. Alessandro Cavecchi
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  3. Frank Thielmann
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  4. Janusz Kulon
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  5. Jag Shur
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  6. Robert Price
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Correspondence to Martin Rowland.

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Rowland, M., Cavecchi, A., Thielmann, F. et al. Measuring The Bipolar Charge Distributions of Fine Particle Aerosol Clouds of Commercial PMDI Suspensions Using a Bipolar Next Generation Impactor (bp-NGI). Pharm Res 36, 15 (2019). https://doi.org/10.1007/s11095-018-2544-9

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  • DOI: https://doi.org/10.1007/s11095-018-2544-9

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