Defense Date

2006

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Pharmaceutics

First Advisor

Dr. Michael Hindle

Abstract

The characterization of perphenazine and scopolamine aerosols generated using the capillary aerosol generator (CAG) was reported. Variables including steady state power, the formulation vehicle, the drug concentration and the formulation flow rate were studied for their effects on the chemical stability and particle size of these drug aerosols.Stability-indicating HPLC and LC-MS assays were developed and validated for perphenazine and scopolamine, respectively. The chemical stability of each compound was investigated under a variety of stress conditions and the structure of degradation products was proposed.Perphenazine aerosols were generated from propylene glycol (PG) formulations with concentrations of 9, 48 and 90mM at formulation flow rates of 2.5 and 5.0µL/s at a series of steady state powers. At higher aerosolization powers, the low concentration formulation (9mM) degraded with dehalogenation being the major pathway. The size of perphenazine aerosols was between 0.4 to 0.6µm. Changing the solute concentration produced only small changes (~0.2µm) in perphenazine aerosol particle size. The formulation flow rate did not significantly affect the aerosol size.Scopolamine degraded significantly when aerosolized in PG formulations. It was possible to generate chemically stable scopolamine aerosols from ethanol formulations. Significant amounts of degradation products were formed only at or above 4.6W at 5.0µL/s. Hydrolysis and dehydration appeared to be the major degradation pathways at higher powers and low formulation flow rate. The MMAD of scopolamine aerosols was between 0.5 and 2.0µm from 8, 20 and 40mM formulations at 5.0 and 10.0µL/s. The size of scopolamine aerosols increased as a function of increasing the solute concentration. Increasing the formulation flow rate increased the linear velocity of the spray, thus the Reynolds number was increased and smaller particles were generated.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

June 2008

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