Jet nebulization of prostaglandin E1 during neonatal mechanical ventilation: stability, emitted dose and aerosol particle size

Pharmacol Res. 2007 Dec;56(6):531-41. doi: 10.1016/j.phrs.2007.09.017. Epub 2007 Oct 2.

Abstract

Background: We have previously reported the safety of aerosolized PGE1 in neonatal hypoxemic respiratory failure. The aim of this study is to characterize the physicochemical properties of PGE1 solution, stability, emitted dose and the aerodynamic particle size distribution (APSD) of PGE1 aerosol in a neonatal ventilator circuit.

Methods: PGE1 was diluted in normal saline and physicochemical properties of the solution characterized. Chemical stability and emitted dose were evaluated during jet nebulization in a neonatal conventional (CMV) or high frequency (HFV) ventilator circuit by a high performance liquid chromatography-mass spectrometry method. The APSD of the PGE1 aerosol was evaluated with a 6-stage cascade impactor during CMV.

Results: PGE1 solution in normal saline had a low viscosity (0.9818 cP) and surface tension (60.8 mN/m) making it suitable for aerosolization. Little or no degradation of PGE1 was observed in samples from aerosol condensates, the PGE1 solution infused over 24h, or the residual solution in the nebulizer. The emitted dose of PGE1 following jet nebulization was 32-40% during CMV and 0.1% during HFV. The PGE1 aerosol had a mass median aerodynamic diameter of 1.4 microm and geometric S.D. of 2.9 with 90% of particles being <4.0 microm in size.

Conclusion: Nebulization of PGE1 during neonatal CMV or HFV is efficient and results in rapid nebulization without altering the chemical structure. On the basis of the physicochemical properties of PGE1 solution and the APSD of the PGE1 aerosol, one can predict predominantly alveolar deposition of aerosolized PGE1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aerosols
  • Alprostadil / analysis*
  • Alprostadil / chemistry
  • Drug Stability
  • Humans
  • Infant, Newborn
  • Nebulizers and Vaporizers*
  • Particle Size
  • Respiration, Artificial*
  • Vasodilator Agents / analysis*
  • Vasodilator Agents / chemistry

Substances

  • Aerosols
  • Vasodilator Agents
  • Alprostadil