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



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


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.


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.


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.


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



Atomic force microscopy


Brunauer, Emmett and Teller


Dry powder inhaler


Dynamic vapor sorption


Electrostatic Low Pressure Impactor


Flame ionization detection


Gas chromatography


High performance liquid chromatography


Relative humidity


Root mean squared


Supercritical CO2


Sodium dodecyl sulfate


Scanning electron microscopy


Salbutamol sulfate


X-ray diffraction



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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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

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