PMID- 25679514
OWN - NLM
STAT- MEDLINE
DCOM- 20160603
LR  - 20151002
IS  - 1941-2703 (Electronic)
IS  - 1941-2711 (Linking)
VI  - 28
IP  - 5
DP  - 2015 Oct
TI  - NanoCluster Itraconazole Formulations Provide a Potential Engineered Drug 
      Particle Approach to Generate Effective Dry Powder Aerosols.
PG  - 341-52
LID - 10.1089/jamp.2014.1155 [doi]
AB  - 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.
FAU - Pornputtapitak, Warangkana
AU  - Pornputtapitak W
AD  - 1 Department of Pharmaceutical Chemistry, University of Kansas , Lawrence, 
      Kansas.
AD  - 3 Department of Chemical Engineering, Faculty of Engineer, Mahidol University, 
      Thailand .
FAU - El-Gendy, Nashwa
AU  - El-Gendy N
AD  - 1 Department of Pharmaceutical Chemistry, University of Kansas , Lawrence, 
      Kansas.
AD  - 4 Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, 
      Beni-suef University , Beni-suef, Egypt .
FAU - Berkland, Cory
AU  - Berkland C
AD  - 1 Department of Pharmaceutical Chemistry, University of Kansas , Lawrence, 
      Kansas.
AD  - 2 Department of Chemical and Petroleum Engineering, University of Kansas , 
      Lawrence, Kansas.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150213
PL  - United States
TA  - J Aerosol Med Pulm Drug Deliv
JT  - Journal of aerosol medicine and pulmonary drug delivery
JID - 101475057
RN  - 0 (Aerosols)
RN  - 0 (Antifungal Agents)
RN  - 304NUG5GF4 (Itraconazole)
MH  - Aerosols
MH  - Antifungal Agents/*chemistry
MH  - Chemistry, Pharmaceutical
MH  - Dry Powder Inhalers
MH  - Itraconazole/administration & dosage/*chemistry
MH  - Nanoparticles
MH  - Particle Size
OTO - NOTNLM
OT  - NanoClusters
OT  - dry powders
OT  - inhalation
OT  - itraconazole
OT  - wet milling
EDAT- 2015/02/14 06:00
MHDA- 2016/06/04 06:00
CRDT- 2015/02/14 06:00
PHST- 2015/02/14 06:00 [entrez]
PHST- 2015/02/14 06:00 [pubmed]
PHST- 2016/06/04 06:00 [medline]
AID - 10.1089/jamp.2014.1155 [doi]
PST - ppublish
SO  - J Aerosol Med Pulm Drug Deliv. 2015 Oct;28(5):341-52. doi: 
      10.1089/jamp.2014.1155. Epub 2015 Feb 13.