Cospray-dried unfractionated heparin with L-leucine as a dry powder inhaler mucolytic for cystic fibrosis therapy

Accumulation of inspissated secretions that are difficult to clear and congest the airways is a feature of lung disease in patients with cystic fibrosis (CF). These secretions restrict airflow, harbour infection and limit the delivery of inhaled drugs including gene therapy vectors to the underlying...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 2008-11, Vol.97 (11), p.4857-4868
Main Authors: Shur, Jagdeep, Nevell, Thomas G., Ewen, Richard J., Price, Robert, Smith, Andrew, Barbu, Eugen, Conway, Joy H., Carroll, Mary P., Shute, Janis K., Smith, James R.
Format: Article
Language:English
Subjects:
Administration, Inhalation
Aerosols
Biological and medical sciences
cospray drying
cystic fibrosis (CF)
dry powder inhaler (DPI)
Expectorants - administration & dosage
Expectorants - chemistry
Expectorants - therapeutic use
force control agent (FCA)
General pharmacology
Heparin - administration & dosage
Heparin - chemistry
Heparin - therapeutic use
Humans
L-leucine
Leucine - administration & dosage
Leucine - chemistry
Leucine - therapeutic use
Medical sciences
Microscopy, Electron, Scanning
Nebulizers and Vaporizers
Particle Size
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Powders
pulmonary drug delivery
Rheology
Spectrum Analysis - methods
spray drying
unfractionated heparin (UFH)
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Summary:Accumulation of inspissated secretions that are difficult to clear and congest the airways is a feature of lung disease in patients with cystic fibrosis (CF). These secretions restrict airflow, harbour infection and limit the delivery of inhaled drugs including gene therapy vectors to the underlying target cells. Unfractionated heparin (UFH) has mucolytic properties suggesting that it may be a useful therapeutic agent for lung disease in these patients. For the pulmonary delivery of UFH to patients with CF, the dry powder inhaler has potential advantages over systems using nebulised suspensions. However, spray-dried particles in the appropriate size range (1–5µm) may absorb atmospheric moisture, causing aggregation. UFH has been cospray-dried with L-leucine (1%, w/w) to produce particles that are less cohesive than UFH alone and show good aerosolisation performance. Rheological analysis has shown that spray-dried UFH and UFH cospray-dried with L-leucine significantly (p 
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.21362