Characterization of heparin aerosols generated in jet and ultrasonic nebulizers

Inhaled heparin has been used for asthma treatment, but results have been inconsistent, probably due to highly varying lung doses. We determined the output per unit time and the particle size distributions of sodium heparin, calcium heparin, and low molecular weight (LMW) heparin formulations in five concentrations from Sidestream jet nebulizers (Medic-Aid, Bognor Regis, England) and an Ultraneb 2000 ultrasonic nebulizer (DeVilbiss, Langen, Germany). We also determined the inhaled mass and the estimated respirable mass for some combinations. For the jet nebulizer, output per minute increased with increasing concentration and flow rate, and particle size decreased from 3.64 to 2.01 microns (mass median diameter [MMD]). The percentage of particles less than 3 microns ranged from 41% to 74%. For the ultrasonic nebulizer, maximum output per minute was achieved at a concentration of 7000 i.u./mL; this maximum depended upon the viscosity and temperature of the solution. MMD was independent of formulation, temperature, or concentration and ranged from 5.61 to 7.03 microns. Sodium heparin/calcium heparin in a concentration of 20,000 i.u./mL in the jet nebulizer driven at 10 L/min produced the highest dose of heparin capable of reaching the lower respiratory tract. Mass balance was determined for these combinations with the jet nebulizer run until visible aerosol generation ceased. Of a loading dose of 80,000 i.u. of heparin, 45,000 i.u. remained in the dead space of the nebulizer, 20,000 i.u. was deposited on the exhalation filter, and 15,000 i.u. was captured on the inhalation filter (inhaled mass). This corresponds to a respirable mass of 10,000 i.u. of heparin with a high probability of reaching the lower respiratory tract in normal healthy adults.