Effects of Nebulization Time and Pressure on Lipid Microtubule Suspension and Aerosol
Titel:
Effects of Nebulization Time and Pressure on Lipid Microtubule Suspension and Aerosol
Auteur:
Johnson, D. L.
Verschenen in:
Aerosol science and technology
Paginering:
Jaargang 30 (1999) nr. 2 pagina's 211-222
Jaar:
1999-02-01
Inhoud:
Lipid microtubules have been suggested as possible drug delivery vehicles in aerosol therapy applications. In our previous work it was shown that tubules of respirable size were aerosolizable from a standard Collison-type air-jet nebulizer. In this work, the effects of nebulization time and pressure on lipid tubules of 1, 2-bis(10, 12-tricosadiynoyl)- sn -glycero-3-phosphocholine (DC8 , 9PC) are examined. Tubules were formed in a 55 percent ethanol:water solution, centrifuged and washed to remove the alcohol, aerosolized at 10, 20, or 30 psi pressure for 60 min using a 3-jet Collison air jet nebulizer, and sampled into an API Aerosizer time-of-flight analyzer at 0, 1, 5, 10, 20, 30, and 60 min nebulization time. Aliquots of tubule suspension were withdrawn from the nebulizer reservoir at the same intervals for length distribution evaluation by light microscopy. Aerosol was also sampled over the 60-min period using a Stober spiral duct centrifuge and the deposited particles optically sized and counted to provide a time-averaged estimate of aerosol size distribution. The lipid particles were straight tubular structures of helically wound bilayer membranes, with 0.6 mu m diameter and log-normal length distribution. During nebulization the tubules underwent significant breakage; suspension tubule lengths decreased in a predictable manner with both increasing nebulization pressure and increasing number of passes through the nozzle. Aerosol aerodynamic size distributions measured with the timeof-flight analyzer were essentially identical for all nebulization pressures and times, and were indistinguishable from the time-averaged size distributions determined from aerosol centrifuge particle deposition data. Comparison of observed aerosol size distribution with expected distribution for an ideal air-jet nebulizer suggested that the Collison nebulizer preferentially aerosolized shorter tubules, consistent with known air-jet nebulizer operation. These results demonstrate that while lipid tubules undergo substantial resizing during nebulization, the resulting aerosol size distribution is stable and of respirable size for at least 60 min nebulization time.