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NanoCluster Itraconazole Formulations Provide a Potential Engineered Drug Particle Approach to Generate Effective Dry Powder Aerosols.
J Aerosol Med Pulm Drug Deliv. 2015 Oct; 28(5):341-52.JA

Abstract

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.

Authors+Show Affiliations

1 Department of Pharmaceutical Chemistry, University of Kansas , Lawrence, Kansas. 3 Department of Chemical Engineering, Faculty of Engineer, Mahidol University, Thailand .1 Department of Pharmaceutical Chemistry, University of Kansas , Lawrence, Kansas. 4 Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-suef University , Beni-suef, Egypt .1 Department of Pharmaceutical Chemistry, University of Kansas , Lawrence, Kansas. 2 Department of Chemical and Petroleum Engineering, University of Kansas , Lawrence, Kansas.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25679514

Citation

Pornputtapitak, Warangkana, et al. "NanoCluster Itraconazole Formulations Provide a Potential Engineered Drug Particle Approach to Generate Effective Dry Powder Aerosols." Journal of Aerosol Medicine and Pulmonary Drug Delivery, vol. 28, no. 5, 2015, pp. 341-52.
Pornputtapitak W, El-Gendy N, Berkland C. NanoCluster Itraconazole Formulations Provide a Potential Engineered Drug Particle Approach to Generate Effective Dry Powder Aerosols. J Aerosol Med Pulm Drug Deliv. 2015;28(5):341-52.
Pornputtapitak, W., El-Gendy, N., & Berkland, C. (2015). NanoCluster Itraconazole Formulations Provide a Potential Engineered Drug Particle Approach to Generate Effective Dry Powder Aerosols. Journal of Aerosol Medicine and Pulmonary Drug Delivery, 28(5), 341-52. https://doi.org/10.1089/jamp.2014.1155
Pornputtapitak W, El-Gendy N, Berkland C. NanoCluster Itraconazole Formulations Provide a Potential Engineered Drug Particle Approach to Generate Effective Dry Powder Aerosols. J Aerosol Med Pulm Drug Deliv. 2015;28(5):341-52. PubMed PMID: 25679514.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - NanoCluster Itraconazole Formulations Provide a Potential Engineered Drug Particle Approach to Generate Effective Dry Powder Aerosols. AU - Pornputtapitak,Warangkana, AU - El-Gendy,Nashwa, AU - Berkland,Cory, Y1 - 2015/02/13/ PY - 2015/2/14/entrez PY - 2015/2/14/pubmed PY - 2016/6/4/medline KW - NanoClusters KW - dry powders KW - inhalation KW - itraconazole KW - wet milling SP - 341 EP - 52 JF - Journal of aerosol medicine and pulmonary drug delivery JO - J Aerosol Med Pulm Drug Deliv VL - 28 IS - 5 N2 - 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. SN - 1941-2703 UR - https://www.unboundmedicine.com/medline/citation/25679514/NanoCluster_Itraconazole_Formulations_Provide_a_Potential_Engineered_Drug_Particle_Approach_to_Generate_Effective_Dry_Powder_Aerosols_ L2 - https://www.liebertpub.com/doi/10.1089/jamp.2014.1155?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -