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Effect of Crystallinity on Electrostatic Charging in Dry Powder Inhaler Formulations

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An Erratum to this article was published on 09 March 2017

ABSTRACT

Purpose

This study aimed to characterize inherent charge generated by micron-sized drug-only formulations of amorphous and crystalline salbutamol sulfate (SS).

Methods

Amorphous SS was produced by spray-drying whilst crystalline SS was produced by conditioning spray-dried SS with supercritical CO2 and menthol. Electrostatic charge of the powders was characterized in two ways. Firstly, the charge profile of the aerosols dispersed from an Aerolizer® was measured using a modified Electrostatic Low Pressure Impactor (ELPI™). Secondly, the net charge of the bulk powders generated from tumbling in containers composed of different materials (polyethylene, polyvinyl chloride, Teflon, nylon and stainless steel) was measured by a Faraday pail.

Results

Following aerosolization, crystalline SS appeared to show more consistent charging and mass deposition than amorphous SS. In the tumbling experiment crystalline SS had a significant correlation between net charge and work function, which was absent in amorphous SS. This may be due to the long-range crystal packing which was reflected as more predictable charging. In addition, the polarity of charging was attributed to the arrangement of SS molecules in the crystal lattice.

Conclusions

The effect of crystallinity on the electrostatic charge behavior of inhalable micron-sized spherical drug particles with well-defined particle size distribution was investigated for the first time. The knowledge gained may assist in the development of optimized inhaled pharmaceutical products.

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Abbreviations

AFM:

Atomic force microscopy

BET:

Brunauer, Emmett and Teller

DPI:

Dry powder inhaler

DVS:

Dynamic vapor sorption

ELPI:

Electrostatic Low Pressure Impactor

FID:

Flame ionization detection

GC:

Gas chromatography

HPLC:

High performance liquid chromatography

RH:

Relative humidity

Rq :

Root mean squared

scCO2 :

Supercritical CO2

SDS:

Sodium dodecyl sulfate

SEM:

Scanning electron microscopy

SS:

Salbutamol sulfate

XRD:

X-ray diffraction

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors thank Ms. Ellen Braybon from Faculty of Chemistry, University of Sydney, for providing instrumental facilities and assistance for GC analysis; the Australian Microscopy & Microanalysis Research Facility, University of Sydney, for providing facilities for SEM imaging; Mr. David Cipolla from Aradigm Corporation for feedback on the manuscript, and Dr. Dai Hibbs from the Faculty of Pharmacy, The University of Sydney, for valuable discussions. This research was supported under Australian Research Council’s Discovery Projects funding scheme (project numbers DP120102778 & 110105161).

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Authors and Affiliations

  1. Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, Sydney, New South Wales, Australia

    Jennifer Wong & Hak-Kim Chan

  2. Department of Pharmacology and Pharmacy Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China

    Philip Chi Lip Kwok

  3. Mexichem UK Limited, The Heath Business and Technical Park, Runcorn, Cheshire, WA7 4QX, UK

    Tim Noakes

  4. School of Chemical and Biomolecular Engineering, The University of Sydney, Sydney, New South Wales, Australia

    Ali Fathi & Fariba Dehghani

Authors
  1. Jennifer Wong
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  2. Philip Chi Lip Kwok
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  3. Tim Noakes
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  4. Ali Fathi
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  5. Fariba Dehghani
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  6. Hak-Kim Chan
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Corresponding author

Correspondence to Hak-Kim Chan.

Additional information

An erratum to this article is available at http://dx.doi.org/10.1007/s11095-017-2125-3.

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Wong, J., Kwok, P.C.L., Noakes, T. et al. Effect of Crystallinity on Electrostatic Charging in Dry Powder Inhaler Formulations. Pharm Res 31, 1656–1664 (2014). https://doi.org/10.1007/s11095-013-1270-6

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  • DOI: https://doi.org/10.1007/s11095-013-1270-6

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