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Niclosamide inhalation powder made by thin-film freezing: Multi-dose tolerability and exposure in rats and pharmacokinetics in hamsters.
Jara, Miguel O; Warnken, Zachary N; Sahakijpijarn, Sawittree; Moon, Chaeho; Maier, Esther Y; Christensen, Dale J; Koleng, John J; Peters, Jay I; Hackman Maier, Sarah D; Williams Iii, Robert O.
  • Jara MO; Molecular Pharmaceutics and Drug Delivery Division, College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, Austin, TX 78712, USA.
  • Warnken ZN; Molecular Pharmaceutics and Drug Delivery Division, College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, Austin, TX 78712, USA. Electronic address: zwarnken@utexas.edu.
  • Sahakijpijarn S; Molecular Pharmaceutics and Drug Delivery Division, College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, Austin, TX 78712, USA.
  • Moon C; Molecular Pharmaceutics and Drug Delivery Division, College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, Austin, TX 78712, USA.
  • Maier EY; Drug Dynamics Institute, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA.
  • Christensen DJ; TFF Pharmaceuticals, Inc., Austin, TX 78746, USA.
  • Koleng JJ; TFF Pharmaceuticals, Inc., Austin, TX 78746, USA.
  • Peters JI; UT- Health San Antonio Department of Medicine, Division of Pulmonary/Critical Care Medicine, San Antonio, TX 78229, USA.
  • Hackman Maier SD; UT- Health San Antonio Department of Pathology, San Antonio, TX 78229, USA.
  • Williams Iii RO; Molecular Pharmaceutics and Drug Delivery Division, College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, Austin, TX 78712, USA. Electronic address: bill.williams@austin.utexas.edu.
Int J Pharm ; 603: 120701, 2021 Jun 15.
Article in English | MEDLINE | ID: covidwho-1225261
Semantic information from SemMedBD (by NLM)
1. Drug Kinetics PROCESS_OF Hamsters
Subject
Drug Kinetics
Predicate
PROCESS_OF
Object
Hamsters
2. Drug Kinetics PROCESS_OF Hamsters
Subject
Drug Kinetics
Predicate
PROCESS_OF
Object
Hamsters
ABSTRACT
In this work, we have developed and tested a dry powder form of niclosamide made by thin-film freezing (TFF) and administered it by inhalation to rats and hamsters to gather data about its toxicology and pharmacokinetics. Niclosamide, a poorly water-soluble drug, is an interesting drug candidate because it was approved over 60 years ago for use as an anthelmintic medication, but recent studies demonstrated its potential as a broad-spectrum antiviral with pharmacological effect against SARS-CoV-2 infection. TFF was used to develop a niclosamide inhalation powder composition that exhibited acceptable aerosol performance with a fine particle fraction (FPF) of 86.0% and a mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) of 1.11 µm and 2.84, respectively. This formulation not only proved to be safe after an acute three-day, multi-dose tolerability and exposure study in rats as evidenced by histopathology analysis, and also was able to achieve lung concentrations above the required IC90 levels for at least 24 h after a single administration in a Syrian hamster model. To conclude, we successfully developed a niclosamide dry powder inhalation that overcomes niclosamide's limitation of poor oral bioavailability by targeting the drug directly to the primary site of infection, the lungs.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 / Niclosamide Limits: Animals / Humans Language: English Journal: Int J Pharm Year: 2021 Document Type: Article Affiliation country: J.ijpharm.2021.120701

Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 / Niclosamide Limits: Animals / Humans Language: English Journal: Int J Pharm Year: 2021 Document Type: Article Affiliation country: J.ijpharm.2021.120701