Effect of Crystallinity on Electrostatic Charging in Dry Powder Inhaler Formulations
- 790 Downloads
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.
KEY WORDScrystallinity 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
High performance liquid chromatography
Root mean squared
Sodium dodecyl sulfate
Scanning electron microscopy
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).
- 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
- 14.Zeng XM, Martin GP, Marriott C. Particulate interactions in dry powder formulations for inhalation. London: Taylor and Francis; 2003.Google Scholar