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Advanced Design and Development of Novel Microparticulate/Nanoparticulate Dry Powder Inhalers Targeting Underlying Mechanisms in Respiratory Diseases

Chronic respiratory diseases such as asthma, COPD, pulmonary fibrosis are more prevalent throughout the world. For some of these diseases there is no cure, the current treatment options manages the symptoms and acute exacerbation. The new approach to find a curative therapy for respiratory diseases is by targeting the cellular / molecular pathways that either cause the disease or has the potential cure the disease. It becomes important to target the respiratory system in treating these diseases to increase the delivered dose and reduce the unwarranted adverse effects. Dry powder inhaler (DPI) is a targeted drug delivery dosage form commonly used to target the airways to treat respiratory diseases. There are two components to dry powder inhaler product – powdered drug formulation and inhaler device; a unified performance of the two is essential for a successful product. In this study, dry powder aerosol of novel drug compounds that targets the underlying cellular and molecular mechanism are developed for the first time. Advanced organic closed mode spray drying technique was used to the produce microparticulate/ nanoparticulate formulations. The formulation of the novel compounds involved utilizing sugar based excipients. Each formulation that was produced was comprehensively characterized in the solid state. The safety of these formulations were tested in in vitro human pulmonary cell lines. The in vitro aerosol dispersion of the spray dried drugs were tested using three FDA approved human inhaler devices. The influence of the inhaler device resistance and spray drying process conditions on the aerosol dispersion was evaluated. Preliminary testing of the formulations in in vivo animal models shows promising results in treating chronic respiratory diseases with these superior aerosol formulations.

Identiferoai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/626331
Date January 2017
CreatorsMuralidharan, Priyadarshini, Muralidharan, Priyadarshini
ContributorsMansour, Heidi M., Mansour, Heidi M., Cherrington, Nathan, Mayersohn, Michael, Myrdal, Paul, Raghavan, Srini
PublisherThe University of Arizona.
Source SetsUniversity of Arizona
Languageen_US
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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