title: Characterization of Ribavirin Aerosol With Small Particle Aerosol Generator and Vibrating Mesh Micropump Aerosol Technologies.
abstract: BACKGROUND
  Ribavirin is an antiviral drug that can be administered by inhalation. Despite advancements in the oral delivery of this medication, there has been a renewed interested in delivering ribavirin via the pulmonary system. Although data are not conclusive that inhaled ribavirin improves outcomes, we set out to determine whether delivery by a newer generation nebulizer, the vibrating mesh micropump, was as effective as the recommended small-particle aerosol generator system.
  
  
  METHODS
  We compared the physicochemical makeup and concentrations of ribavirin before and after nebulization with 0.9% NaCl and sterile water. An Andersen cascade impactor was used to determine particle size distribution and mass median aerodynamic diameter, and an absolute filter was used to measure total aerosol emitted output and inhaled dose during mechanical ventilation and spontaneous breathing. Ribavirin was analyzed and quantified using high-performance liquid chromatography with tandem mass spectrometric detection.
  
  
  RESULTS
  Ribavirin was found to be stable in both 0.9% aqueous NaCl and sterile water with an r(2) value of 0.96 and identical coefficients of variation with no difference in drug concentration before and after nebulization with the vibrating mesh micropump. The small-particle aerosol generator produced a smaller mass median aerodynamic diameter (1.84 μm) than the vibrating mesh micropump (3.63 μm, P = .02); however, there was no significant difference in the proportion of drug mass in the 0.7-4.7-μm particle range. Total drug delivery was similar with the small-particle aerosol generator and vibrating mesh micropump in both spontaneously breathing (P = .77) and mechanical ventilation (P = .48) models.
  
  
  CONCLUSIONS
  The vibrating mesh micropump nebulizer may provide an effective alternative to the small-particle aerosol generator in administration of ribavirin using NaCl or sterile water, both on and off the ventilator. Further clinical studies are needed to compare efficacy.
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine Department of Anesthesia, Harvard Medical School is also affiliated with the Department of Anesthesia, Harvard Medical School, Boston, Massachusetts. brian.walsh@childrens.harvard.edu.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Walsh
authors.affiliation: Department of Respiratory Care, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Peter
authors.initials: P
authors.lastname: Betit
authors.affiliation: James B Fink, LLC, San Mateo, California, and the Department of Respiratory Therapy, Georgia State University, Atlanta, Georgia.
authors.forename: James B
authors.initials: JB
authors.lastname: Fink
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Pereira
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine Department of Anesthesia, Harvard Medical School is also affiliated with the Department of Anesthesia, Harvard Medical School, Boston, Massachusetts. Department of Critical Care Medicine, Children's Hospital, Boston, Massachusetts.
authors.forename: John
authors.initials: J
authors.lastname: Arnold
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols / Q000008:administration & dosage; D000998:Antiviral Agents / Q000008:administration & dosage*; D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008962:Models, Theoretical; D009330:Nebulizers and Vaporizers; D012254:Ribavirin / Q000008:administration & dosage*; D053719:Tandem Mass Spectrometry
chemical_list: D000336:Aerosols; D000998:Antiviral Agents; D012254:Ribavirin
keywords: mass median aerodynamic diameter; mechanical ventilation; ribavirin; small-particle aerosol generator; vibrating mesh nebulizer