Advertisement

Pharmaceutical Research

, Volume 31, Issue 7, pp 1656–1664 | Cite as

Effect of Crystallinity on Electrostatic Charging in Dry Powder Inhaler Formulations

  • Jennifer Wong
  • Philip Chi Lip Kwok
  • Tim Noakes
  • Ali Fathi
  • Fariba Dehghani
  • Hak-Kim Chan
Research Paper

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.

KEY WORDS

crystallinity dry powder inhaler (DPI) electrostatic charge salbutamol sulfate supercritical fluid 

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

Notes

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).

REFERENCES

  1. 1.
    Wong J, Chan H-K, Kwok PCL. Electrostatics in pharmaceutical aerosols for inhalation. Ther Deliv. 2013;4:981–1002.CrossRefPubMedGoogle Scholar
  2. 2.
    Byron PR, Peart J, Staniforth JN. Aerosol electrostatics I: properties of fine powders before and after aerosolization by dry powder inhalers. Pharm Res. 1997;14:698–705.CrossRefPubMedGoogle Scholar
  3. 3.
    Telko MJ, Kujanpaa J, Hickey AJ. Investigation of triboelectric charging in dry powder inhalers using electrical low pressure impactor (ELPI). Int J Pharm. 2007;336:352–60.CrossRefPubMedGoogle Scholar
  4. 4.
    Kwok PCL, Chan HK. Effect of relative humidity on the electrostatic charge properties of dry powder inhaler aerosols. Pharm Res. 2008;25:277–88.CrossRefPubMedGoogle Scholar
  5. 5.
    Young P, Sung A, Traini D, Kwok P, Chiou H, Chan H-K. Influence of humidity on the electrostatic charge and aerosol performance of dry powder inhaler carrier based systems. Pharm Res. 2007;24:963–70.CrossRefPubMedGoogle Scholar
  6. 6.
    Karner S, Anne Urbanetz N. The impact of electrostatic charge in pharmaceutical powders with specific focus on inhalation-powders. J Aerosol Sci. 2011;42:428–45.CrossRefGoogle Scholar
  7. 7.
    Kwok PCL, Chan HK. Electrostatics of pharmaceutical inhalation aerosols. J Pharm Pharmacol. 2009;61:1587–99.CrossRefPubMedGoogle Scholar
  8. 8.
    Murtomaa M, Harjunen P, Mellin V, Lehto V-P, Laine E. Effect of amorphicity on the triboelectrification of lactose powder. J Electrost. 2002;56:103–10.CrossRefGoogle Scholar
  9. 9.
    Kwok PCL, Chan HK. Solid forms and electrostatic properties of salbutamol sulfate. In Dalby R, editors. Respiratory drug delivery, vol. 3, River Grove; 2008, pp. 919–22.Google Scholar
  10. 10.
    Adi H, Kwok PCL, Crapper J, Young PM, Traini D, Chan H-K. Does electrostatic charge affect powder aerosolisation? J Pharm Sci. 2010;99:2455–61.CrossRefPubMedGoogle Scholar
  11. 11.
    Muhammad SA, Langrish T, Tang P, Adi H, Chan H-K, Kazarian SG, et al. A novel method for the production of crystalline micronised particles. Int J Pharm. 2010;388:114–22.CrossRefPubMedGoogle Scholar
  12. 12.
    Xie S, Poornachary SK, Chow PS, Tan RBH. Direct precipitation of micron-size salbutamol sulfate: new insights into the action of surfactants and polymeric additives. Cryst Growth Des. 2010;10:3363–71.CrossRefGoogle Scholar
  13. 13.
    Gallo CF, Lama WL. Classical electrostatic description of the work function and ionization energy of insulators. IEEE Trans Ind Appl. 1976;12:7–11.CrossRefGoogle Scholar
  14. 14.
    Zeng XM, Martin GP, Marriott C. Particulate interactions in dry powder formulations for inhalation. London: Taylor and Francis; 2003.Google Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Jennifer Wong
    • 1
  • Philip Chi Lip Kwok
    • 2
  • Tim Noakes
    • 3
  • Ali Fathi
    • 4
  • Fariba Dehghani
    • 4
  • Hak-Kim Chan
    • 1
  1. 1.Advanced Drug Delivery Group, Faculty of PharmacyThe University of SydneySydneyAustralia
  2. 2.Department of Pharmacology and Pharmacy Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina
  3. 3.Mexichem UK Limited, The Heath Business and Technical ParkRuncornUK
  4. 4.School of Chemical and Biomolecular EngineeringThe University of SydneySydneyAustralia

Personalised recommendations