Defense Date

2008

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Pharmaceutics

First Advisor

Joanne Peart

Abstract

Aerosol electrostatics is an important property of pharmaceutical aerosols. The electrostatic properties of pMDI aerosols have been shown to be a function of both formulation and packaging components. The modified ELPI enables measurement of aerosol charge as a function of particle size, and the simultaneous determination of the mass distribution using chemical analysis. However, in order to fully assess the cause and effects of aerosol electrostatics in terms of its biological and regulatory implications, it is necessary to understand the basic charging mechanisms inside the pMDI formulation.

Electrical resistivity and zeta potential measurements confirmed the presence of charged species within HFA based solutions and suspensions although the nature of these species remains unknown. These measurements were influenced by the cosolvent concentration and to a lesser extent by the presence of soluble drug and surfactant. The mean electrical resistivity of a 7% ethanol / 93% HFA 134a blend (0.83 ± 0.02 MΩ.cm) was significantly lower than that reported for HFA 134a (180 MΩ.cm). Albuterol sulfate demonstrated a positive zeta potential (75.9 ± 26.2 mV) in HFA 134a. Pilot molecular modeling studies, in conjunction with the analysis of particle interactions using HINT, provided an improved understanding of the possible interactions within albuterol sulfate HFA suspension pMDIs. The predominantly negative (-7597 ± 2063) HINT score signified unfavorable interactions between albuterol sulfate and HFA 134a molecules.

Systematic investigations of the electrical properties of HFA solution and suspension pMDIs using the modified ELPI demonstrated that the electrical properties were a function of the formulation type (solution/suspension), formulation components and particle size. Experimental BDP solution pMDIs produced predominantly electropositive aerosols (net charge: 160 ± 30 pC) while albuterol sulfate pMDIs produced bipolar charged aerosol clouds (net charge: -162 ± 277 pC). Finally, the modified ELPI was recalibrated using commercially available polydisperse pMDIs as calibration aerosols with a reference Andersen cascade impactor. The mean cut-off diameters for stages 4-12 obtained following recalibration of the modified ELPI were 0.44, 0.56, 0.70, 1.01, 1.40, 2.12, 3.03, 4.75, 6.37 μm, respectively in comparison to those reported by the manufacturer (0.16, 0.27, 0.39, 0.62, 0.96, 1.62, 2.42, 4.05, 6.67 μm, respectively).

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

August 2008

Share

COinS