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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/36861
Title: NanoCluster Itraconazole Formulations Provide a Potential Engineered Drug Particle Approach to Generate Effective Dry Powder Aerosols
Authors: Warangkana Pornputtapitak
Nashwa El-Gendy
Cory Berkland
University of Kansas Lawrence
Mahidol University
Beni-Suef University
Keywords: Medicine
Issue Date: 1-Jan-2015
Citation: Journal of Aerosol Medicine and Pulmonary Drug Delivery. Vol.28, No.5 (2015), 341-352
Abstract: © Copyright 2015, Mary Ann Liebert, Inc. 2015. Background: Itraconazole (ITZ), a triazole antifungal agent, is a poorly water-soluble drug that is orally administered for treatment of fungal infections such as allergic bronchopulmonary aspergillosis (ABPA) and invasive aspergillosis (IA). ABPA is relatively well controlled but IA can be fatal, especially in immunosuppressed patients. Aerosolized ITZ delivered to the lung may provide a local treatment and prophylaxis against IA at the primary site of infection in the lungs. Variations of the percent fine particle fraction (FPF), the percent emitted dose, and the physical properties of the aerosol (e.g., crystallinity) can confound consistent delivery. Methods: ITZ NanoClusters were formulated via milling (top-down process) or precipitation (bottom-up process) without using any excipients. Itraconazole formulations (ITZ) were prepared by milling 1 gram of micronized itraconazole in 300 mL of fluid. The suspension was collected at 0.5, 1, and 2 hours milling time. Milled ITZ was compared to ITZ prepared by anti-solvent precipitation and to the stock micronized itraconazole. The aerosolization performance of ITZ formulations was determined using an Andersen Cascade Impactor (ACI). Results: The physicochemical properties and aerosol performance of different ITZ NanoClusters suggested an optimized wet milling was the preferred process compared to precipitation. ITZ NanoClusters prepared by wet milling showed better aerosol performance compared to micronized ITZ as received and ITZ NanoClusters prepared by precipitation. ITZ NanoClusters prepared by precipitation methods also showed an amorphous state, while ITZ milled in 10% EtOH maintained the crystalline character of ITZ throughout a 2 hour milling time. Conclusions: The aerosol performance of milled ITZ NanoClusters was dramatically improved compared to micronized ITZ as received due to the difference of drug particle structures. ITZ NanoCluster formulations represent a potential engineered drug particle approach for inhalation therapy, providing effective aerosol properties and stability due to the crystalline state of the drug powders.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84943241089&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/36861
ISSN: 19412703
19412711
Appears in Collections:Scopus 2011-2015

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