Characterization of heparin aerosols generated in jet and ultrasonic nebulizers

Inhaled heparin has been used for asthma treatment, but results have been i nconsistent, probably due to highly varying lung doses. We determined the o utput per unit time and the particle size distributions of sodium heparin, calcium heparin, and low molecular weight (LMW) heparin formulations in fiv e concentrations from Sidestream jet nebulizers (Medic-Aid, Bognor Regis, E ngland) and an Ultraneb 2000 ultrasonic nebulizer (DeVilbiss, Langen, Germa ny). We also determined the inhaled mass and the estimated respirable mass for some combinations. For the jet nebulizer, output per minute increased w ith increasing concentration and flow rate, and particle size decreased fro m 3.64 to 2.01 mu m (mass median diameter [MMD]). The percentage of particl es less than 3 mu m ranged from 41% to 74%. For the ultrasonic nebulizer, m aximum output per minute was achieved at a concentration of 7000 IU/mL; thi s maximum depended upon the viscosity and temperature of the solution. MMD was independent of formulation, temperature, or concentration and ranged fr om 5.61 to 7.03 mu m. Sodium heparin/calcium heparin in a concentration of 20,000 IU/mL in the jet nebulizer driven at 10 L/min produced the highest d ose of heparin capable of reaching the lower respiratory tract. Mass balanc e was determined for these combinations with the jet nebulizer run until vi sible aerosol generation ceased. Of a loading dose of 80,000 IU of heparin, 45,000 IU remained in the dead space of the nebulizer, 20,000 IU was depos ited on the exhalation filter, and 15,000 IU was captured on the inhalation filter (inhaled mass). This corresponds to a respirable mass of 10,000 IU of heparin with a high probability of reaching the lower respiratory tract in normal healthy adults.