Investigation of electrostatic charging phenomena in dry powder inhalers and the effect on deposition Public Deposited

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Last Modified
  • March 21, 2019
Creator
  • Telko, Martin Jan
    • Affiliation: Eshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics
Abstract
  • Dry powder inhalers (DPI) are an important drug delivery option, for the treatment of respiratory diseases, and, increasingly, for the delivery of systemically acting drugs and vaccines. Most DPI formulations consist of micronized drug blended with larger carrier particles. The interactions between drug and carrier are a major determinant of DPI performance. Electrostatic interactions between particles are recognized as one mode of particle interaction. Simulations, in vitro and in vivo studies indicate that electrostatic charge affects the delivery and deposition of aerosol particles in the lung. Yet, the occurrence and origins of electrostatic charge on medicinal aerosol particles are poorly investigated and understood. The major physicochemical properties of two drugs (albuterol sulfate and budesonide) and a number of excipients (lactose, glucose and calcium phosphate) were assessed. Deposition studies with model formulations using the electrical low pressure impactor showed that micronized drug particles are subject to significant triboelectrification. Particle charge levels were shown to be several orders of magnitude larger than had previously been estimated. A multivariate experimental design framework was employed to investigate the effects of various formulation factors on the charging of the two drugs; it was shown that several formulation variables, in particular the excipient, have profound effects on charge acquired by micronized drug particles available to the lungs. The charging behavior observed in deposition studies agreed largely with bulk electrostatic measurements conducted on the raw materials. It was thus concluded that the origin of the charge was contact charging between particles of the formulation. The charging behavior was further elucidated through inverse gas chromatography measurements, in which the surface acid/base properties of the excipients were determined. Surface acid/base parameters, which characterize the tendency of a material to act as electron donor or acceptor in intermolecular interactions, correlated with the charges obtained in Faraday well experiments and particle charges acquired during DPI actuation, which suggests the three phenomena are closely related. The rank-order observed (from least to most electron withdrawing) was albuterol, lactose, glucose, calcium phosphate, budesonide. The study provides a mean of characterization that can be used to predict charging propensity which can assist the DPI product development process.
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  • In Copyright
Advisor
  • Hickey, Anthony J.
Degree granting institution
  • University of North Carolina at Chapel Hill
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  • Open access
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