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Studies in Aerosol Drug Formulation, Analysis, and Modeling

A recently mandated change in the use of pharmaceutical propellants spurred the development and reevaluation of aerosolized pharmaceuticals. Chlorofluorocarbon (CFC) propellants were commonly used in pressurized metered dose inhalers (MDIs), but were unfortunately linked to the depletion of the ozone layer. As such, a search for new propellants was initiated and ultimately resulted in the implementation of hydrofluoroalkane (HFA) propellants in MDIs. These HFA propellants however demonstrated significantly different properties than CFCs and necessitated a considerable amount of reformulation efforts. Not only did HFAs demonstrate different physiochemical properties, but in some cases these differences necessitated reengineering of the delivery device. Unfortunately HFA propellants are considered greenhouse gasses, albeit to a lesser degree than CFCs, so the development of alternate delivery methods has been ongoing. One delivery method that has received significant attention and resources is dry powder inhalers (DPIs). DPIs are a propellant-free alternative to aerosolized drug delivery, and demonstrate some advantages and disadvantages compared to the use of MDIs and nebulizers.In addition to the modernization of pharmaceutical agents, excipients, and delivery devices, technological advances have allowed for different and/or improved characterization of pharmaceutical aerosols. Particle size characteristics of aerosols are the primary physical measure examined and are relevant to ensure proper and reproducible drug delivery to the lung. Likewise, chemical analysis of the pharmaceutical agent is extremely important for pharmaceutical development and monitoring, including solubility determination, stability monitoring, and ultimately, dose emitted. Because many limitations exist in characterization however, and because experimental means can be costly with regard to labor and materials, prediction of aerosol performance characteristics based on formulation and device variables are valuable.Previous work predicting the performance of solution based MDIs has opened the door for improved prediction of suspension based MDI systems. Suspension aerosol prediction has been examined in the past, but additional information is now available to more appropriately model suspension MDI systems that include polydisperse drug material and emit polydisperse droplets.

Identiferoai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/194099
Date January 2008
CreatorsMogalian, Erik
ContributorsMyrdal, Paul B, Myrdal, Paul B, Yalkowsky, Samuel, Mayersohn, Michael
PublisherThe University of Arizona.
Source SetsUniversity of Arizona
LanguageEnglish
Detected LanguageEnglish
Typetext, Electronic Dissertation
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.

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